Selenium Tissue Distribution Changes After Ethanol Exposure During Gestation and Lactation: Selenite As a Therapy

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Oct, 2009  |  Pubmed ID: 19596040

Ethanol consumption affects maternal nutrition and antioxidant status together with the future health of their progeny. Selenium (Se) is a trace element with antioxidant activity; we will study the effect of ethanol in dams on Se bioavailability, antioxidant balance and gestational parameters. We also will study if a Se-supplemented diet (0.5 ppm) administered to ethanol-exposed dams avoids the undesirable effects provoked by ethanol. We have used four experimental groups: control (C); chronic ethanol (A); control+Se (CS) and chronic ethanol+Se (AS). Se levels in serum, urine, faeces, and several tissues were measured by graphite-furnace atomic absorption spectrometry. Serum glutathione peroxidase (GPx) activity was determined by spectrometry. Se bioavailability is altered by ethanol, causing a decrease in Se retention, reducing Se levels in cortex, muscle, mammary gland and salivary gland while elevating Se values in heart, liver and spleen. On the other hand, Se supplementation increases some of these parameters. Serum GPx activity was decreased by ethanol, while a Se-supplemented diet restores these values to those found in controls. We have demonstrated that ethanol decreased Se retention in dams, affecting their tissues' Se deposits, decreasing GPx activity in serum, gestational parameters and the weight of their progeny. Selenite supplementation counteracts these decreasing effects, except in cortex.

Optimization of the Treatment of Wheat Samples for the Determination of Phytic Acid by HPLC with Refractive Index Detection

Journal of AOAC International. May-Jun, 2009  |  Pubmed ID: 19610380

The treatment of wheat samples was optimized before the determination of phytic acid by high-performance liquid chromatography with refractive index detection. Drying by lyophilization and oven drying were studied; drying by lyophilization gave better results, confirming that this step is critical in preventing significant loss of analyte. In the extraction step, washing of the residue and collection of this water before retention of the phytates in the NH2 Sep-Pak cartridge were important. The retention of phytates in the NH2 Sep-Pak cartridge and elimination of the HCI did not produce significant loss (P = 0.05) in the phytic acid content of the sample. Recoveries of phytic acid averaged 91%, which is a substantial improvement with respect to values reported by others using this methodology.

[Comparison of Neuropsychological Performance According to the Age of Onset in Subjects with Parkinson's Disease and Parkinsonism]

Revista De Neurologia. Aug 1-15, 2009  |  Pubmed ID: 19621306

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, and it is characterised by tremor, bradykinesia, rigidity and postural instability. The most frequent cognitive disorder is executive dysfunction, although global deficits associated to late onset of the disease have also been reported.

Morphological Evidence of Muscular Connections Between Contiguous Pulmonary Venous Orifices: Relevance of the Interpulmonary Isthmus for Catheter Ablation in Atrial Fibrillation

Heart Rhythm : the Official Journal of the Heart Rhythm Society. Aug, 2009  |  Pubmed ID: 19632632

Electrophysiological studies in patients with atrial fibrillation demonstrated the presence of electrical conduction between superior and inferior left pulmonary veins (PVs) that makes electrical disconnection of individual PVs difficult. Anatomically, the prevalence, sizes, and locations of the interpulmonary connections have not been investigated systematically.

Efficacy of High Doses of Daptomycin Versus Alternative Therapies Against Experimental Foreign-body Infection by Methicillin-resistant Staphylococcus Aureus

Antimicrobial Agents and Chemotherapy. Oct, 2009  |  Pubmed ID: 19635963

Since the currently approved dose of daptomycin (6 mg/kg of body weight/day) has been associated with clinical failures and resistance development, higher doses for some difficult-to-treat infections are being proposed. We studied the efficacy of daptomycin at high doses (equivalent to 10 mg/kg/day in humans) and compared it to that of reference and alternative treatments in a model of foreign-body infection with methicillin (meticillin)-resistant Staphylococcus aureus. In vitro studies were conducted with bacteria in the log and stationary phases. For the in vivo model, therapy with daptomycin at 100 mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin (rifampicin) at 25 mg/kg/12 h, or linezolid at 35 mg/kg/12 h was administered for 7 days. Antibiotic efficacy was evaluated using either bacteria from tissue cage fluids or those attached to coverslips. We screened for the emergence of linezolid- and rifampin-resistant strains and analyzed the surviving population from the daptomycin-treated group. Only daptomycin was bactericidal in both the log- and stationary-phase studies. Daptomycin (decrease in the log number of CFU per milliliter of tissue cage fluid, 2.57) and rifampin (decrease, 2.6 log CFU/ml) were better (P < 0.05) than vancomycin (decrease, 1.1 log CFU/ml) and linezolid (decrease, 0.9 log CFU/ml) in the animal model. Rifampin-resistant strains appeared in 60% of cases, whereas no linezolid resistance emerged. No daptomycin-resistant subpopulations were detected at frequencies of 10(-7) or higher. In conclusion, daptomycin at high doses proved to be as effective as rifampin, and the two were the most active therapies for this experimental foreign-body infection. These high doses ensured a profile of safety from the development of resistance.

In Vivo Depletion of DC Impairs the Anti-tumor Effect of Agonistic Anti-CD137 MAb

European Journal of Immunology. Sep, 2009  |  Pubmed ID: 19662633

Anti-CD137 mAb are capable of inducing tumor rejection in several syngeneic murine tumor models and are undergoing clinical trials for cancer. The anti-tumor effect involves co-stimulation of tumor-specific CD8(+) T cells. Whether antigen cross-presenting DC are required for the efficacy of anti-CD137 mAb treatment has never been examined. Here we show that the administration of anti-CD137 mAb eradicates EG7-OVA tumors by a strictly CD8beta(+) T-cell-dependent mechanism that correlates with increased CTL activity. Ex vivo analyses to determine the identity of the draining lymph node cell type responsible for tumor antigen cross-presentation revealed that CD11c(+) cells, most likely DC, are the main players in this tumor model. A minute number of tumor cells, revealed by the presence of OVA cDNA, reach tumor-draining lymph nodes. Direct antigen presentation by tumor cells themselves also participates in anti-OVA CTL induction. Using CD11c diphtheria toxin receptor-green fluorescent protein-->C57BL/6 BM chimeric mice, which allow for sustained ablation of DC with diphtheria toxin, we confirmed the involvement of DC in tumor antigen cross-presentation in CTL induction against OVA(257-264) epitope and in the antitumor efficacy induced by anti-CD137 mAb.

Functional Equivalence of HMGA- and Histone H1-like Domains in a Bacterial Transcriptional Factor

Proceedings of the National Academy of Sciences of the United States of America. Aug, 2009  |  Pubmed ID: 19666574

Histone H1 and high-mobility group A (HMGA) proteins compete dynamically to modulate chromatin structure and regulate DNA transactions in eukaryotes. In prokaryotes, HMGA-like domains are known only in Myxococcus xanthus CarD and its Stigmatella aurantiaca ortholog. These have an N-terminal module absent in HMGA that interacts with CarG (a zinc-associated factor that does not bind DNA) to form a stable complex essential in regulating multicellular development, light-induced carotenogenesis, and other cellular processes. An analogous pair, CarD(Ad) and CarG(Ad), exists in another myxobacterium, Anaeromyxobacter dehalogenans. Intriguingly, the CarD(Ad) C terminus lacks the hallmark HMGA DNA-binding AT-hooks and instead resembles the C-terminal region (CTR) of histone H1. We find that CarD(Ad) alone could not replace CarD in M. xanthus. By contrast, when introduced with CarG(Ad), CarD(Ad) functionally replaced CarD in regulating not just 1 but 3 distinct processes in M. xanthus, despite the lower DNA-binding affinity of CarD(Ad) versus CarD in vitro. The ability of the cognate CarD(Ad)-CarG(Ad) pair to interact, but not the noncognate CarD(Ad)-CarG, rationalizes these data. Thus, in chimeras that conserve CarD-CarG interactions, the H1-like CTR of CarD(Ad) could replace the CarD HMGA AT-hooks with no loss of function in vivo. More tellingly, even chimeras with the CarD AT-hook region substituted by human histone H1 CTR or full-length H1 functioned in M. xanthus. Our domain-swap analyses showing functional equivalence of HMGA AT-hooks and H1 CTR in prokaryotic transcriptional regulation provide molecular insights into possible modes of action underlying their biological roles.

Pilot Study of Ampicillin-ceftriaxone Combination for Treatment of Orthopedic Infections Due to Enterococcus Faecalis

Antimicrobial Agents and Chemotherapy. Oct, 2009  |  Pubmed ID: 19667290

Serious Enterococcus faecalis infections usually require combination therapy to achieve a bactericidal effect. In orthopedic infections, the prognosis of enterococcal etiology is considered poor, and the use of aminoglycosides is questioned. The ampicillin-ceftriaxone combination has recently been accepted as alternative therapy for enterococcal endocarditis. After one of our patients with endocarditis and vertebral osteomyelitis was cured with ampicillin-ceftriaxone, we started a pilot study of orthopedic infections. Patients with infections due to E. faecalis (with two or more surgical samples or blood cultures) diagnosed during 2005 to 2008 were recruited. Polymicrobial infections with ampicillin- and ceftriaxone-resistant microorganisms were excluded. Patients received ampicillin (8 to 16 g/day)-ceftriaxone (2 to 4 g/day) and were followed up prospectively. Of 31 patients with E. faecalis infections, 10 received ampicillin-ceftriaxone. Including the first patient, 11 patients were treated with ampicillin-ceftriaxone: 3 with prosthetic joint infections, 3 with instrumented spine arthrodesis device infections, 2 with osteosynthesis device infections, 1 with foot osteomyelitis, and 2 with vertebral osteomyelitis and endocarditis. Six infections (55%) were polymicrobial. All cases except the vertebral osteomyelitis ones required surgery, with retention of foreign material in six cases. Ampicillin-ceftriaxone was given for 25 days (interquartile range, 15 to 34 days), followed by amoxicillin (amoxicilline) being given to seven patients (64%). One patient with endocarditis died within 2 weeks (hemorrhagic stroke) and was not evaluable. For one patient with prosthesis retention, the infection persisted; 9/10 patients (90%) were cured, but 1 patient was superinfected. Follow-up was for 21 months (interquartile range, 14 to 36 months). Ampicillin-ceftriaxone may be a reasonable synergistic combination to treat orthopedic infections due to E. faecalis. Our experience, though limited, shows good outcomes and tolerability and may provide a basis for further well-designed comparative studies.

Recovery of Nonpathogenic Mutant Bacteria from Tumors Caused by Several Agrobacterium Tumefaciens Strains: a Frequent Event?

Applied and Environmental Microbiology. Oct, 2009  |  Pubmed ID: 19700547

We have evaluated the interaction that bacterial genotypes and plant hosts have with the loss of pathogenicity in tumors, using seven Agrobacterium tumefaciens strains inoculated on 12 herbaceous and woody hosts. We performed a screening of the agrobacteria present inside the tumors, looking for nonpathogenic strains, and found a high variability of those strains in this niche. To verify the origin of the putative nonpathogenic mutant bacteria, we applied an efficient, reproducible, and specific randomly amplified polymorphic DNA analysis method. In contrast with previous studies, we recovered a very small percentage (0.01%) of nonpathogenic strains that can be considered true mutants. Of 5,419 agrobacterial isolates examined, 662 were nonpathogenic in tomato, although only 7 (from pepper and tomato tumors induced by two A. tumefaciens strains) could be considered to derive from the inoculated strain. Six mutants were affected in the transferred DNA (T-DNA) region; one of them contained IS426 inserted into the iaaM gene, whereas the whole T-DNA region was apparently deleted in three other mutants, and the virulence of the remaining two mutants was fully restored with the T-DNA genes as well. The plasmid profile was altered in six of the mutants, with changes in the size of the Ti plasmid or other plasmids and/or the acquisition of new plasmids. Our results also suggest that the frequent occurrence of nonpathogenic clones in the tumors is probably due to the preferential growth of nonpathogenic agrobacteria, of either endophytic or environmental origin, but different from the bacterial strain inducing the tumor.

[Cutaneous Sclerosing Perineurioma]

Actas Dermo-sifiliográficas. Jul-Aug, 2009  |  Pubmed ID: 19709561

Ethanol Consumption by Wistar Rat Dams Affects Selenium Bioavailability and Antioxidant Balance in Their Progeny

International Journal of Environmental Research and Public Health. Aug, 2009  |  Pubmed ID: 19742151

Ethanol consumption affects maternal nutrition, the mothers' antioxidant balance and the future health of their progeny. Selenium (Se) is a trace element cofactor of the enzyme glutathione peroxidase (GPx). We will study the effect of ethanol on Se bioavailability in dams and in their progeny. We have used three experimental groups of dams: control, chronic ethanol and pair-fed; and three groups of pups. Se levels were measured by graphite-furnace atomic absorption spectrometry. Serum and hepatic GPx activity was determined by spectrometry. We have concluded that ethanol decreased Se retention in dams, affecting their tissue Se deposits and those of their offspring, while also compromising their progeny's weight and oxidation balance. These effects of ethanol are caused by a reduction in Se intake and a direct alcohol-generated oxidation action.

Intracellular Antimicrobial Activity Appearing As a Relevant Factor in Antibiotic Efficacy Against an Experimental Foreign-body Infection Caused by Staphylococcus Aureus

The Journal of Antimicrobial Chemotherapy. Nov, 2009  |  Pubmed ID: 19744977

The presence of bacterial biofilm, tolerance to antibiotics and dysfunctional activity of phagocytic cells are all related to difficulties in eradicating foreign-body infections. We aimed to quantify the presence of intracellular Staphylococcus aureus and to study the extent to which the intracellular activity of antibiotics might determine their efficacy against an experimental rat tissue-cage model of foreign-body infection.

Genome-wide Association and Replication Studies Identify Four Variants Associated with Prostate Cancer Susceptibility

Nature Genetics. Oct, 2009  |  Pubmed ID: 19767754

We report a prostate cancer genome-wide association follow-on study. We discovered four variants associated with susceptibility to prostate cancer in several European populations: rs10934853[A] (OR = 1.12, P = 2.9 x 10(-10)) on 3q21.3; two moderately correlated (r2 = 0.07) variants, rs16902094[G] (OR = 1.21, P = 6.2 x 10(-15)) and rs445114[T] (OR = 1.14, P = 4.7 x 10(-10)), on 8q24.21; and rs8102476[C] (OR = 1.12, P = 1.6 x 10(-11)) on 19q13.2. We also refined a previous association signal on 11q13 with the SNP rs11228565[A] (OR = 1.23, P = 6.7 x 10(-12)). In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, we estimated that carriers in the top 1.3% of the risk distribution are at a 2.5 times greater risk of developing the disease than members of the general population.

Cryoablation Time-dependent Dose-response Effect at Minimal Temperatures (-80 Degrees C): an Experimental Study

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. Nov, 2009  |  Pubmed ID: 19846431

To establish a temporal safety window for cryoablation at minimal temperatures and to assess the electrophysiological and histological changes as a function of the application duration.

Deguelin Inhibits Growth of Breast Cancer Cells by Modulating the Expression of Key Members of the Wnt Signaling Pathway

Cancer Prevention Research (Philadelphia, Pa.). Nov, 2009  |  Pubmed ID: 19861542

An emphasis in early detection and more effective treatments has decreased the mortality rate of breast cancer. Despite this decrease, breast cancer continues to be the leading cause of death among women between 40 and 55 years of age and is the second overall cause of death among women. Hence, the aim of the present study was to assess the therapeutic efficacy of deguelin, a rotenoid isolated from several plant species, which has been reported to have chemopreventive and/or chemotherapeutic effects in skin, mammary, colon, and lung cancers. The effect of deguelin on cell proliferation was evaluated using four human breast carcinoma cell lines (MCF-7, BT474, T47D, and MDA-MB-231) by cell count and MTT. Moreover, apoptosis was evaluated by acridine/ethidium staining and DNA laddering. Gene expression changes following deguelin treatment in MDA-MB-231 cells was assessed through microarray analysis. Deguelin at 1 mumol/L was found to inhibit the growth of the breast cancer cell lines tested with a range of 37% to 87%. The highest inhibition was noted for the MDA-MB-231 cell line (MDA-MB-231>BT474>MCF7>T47D>MCF12F). An arrest at the S phase of the cell cycle and apoptosis were shown in the MDA-MB-231 cells treated with deguelin. The microarray profile indicated differential expression of two independent pathways, including clusters of apoptosis and Wnt/beta-catenin signaling genes in cells as a result of deguelin treatment. These studies support the antiproliferative effects of deguelin in human breast cancer cells and, perhaps more importantly, illustrate novel actions by deguelin in the Wnt signaling pathway.

Influence of Bonding Mode of the Linkers in the Electronic Communication of Molecular Pairs Having Dimolybdenum Units Linked by Pseudohalides

Inorganic Chemistry. Dec, 2009  |  Pubmed ID: 19883109

Depending on conditions the reactions of [Mo(2)(cis-DAniF)(2)(NCCH(3))(4)](BF(4))(2) (DAniF = N,N'-di-p-anisylformamidinate) with solutions containing thiocyanate anions lead to two compounds: a quadruple-bonded dinuclear species 1, (Bu(n)(4)N)(2)[Mo(2)(cis-DAniF)(2)(NCS)(4)], and a molecular pair 3, [Mo(2)(cis-DAniF)(2)](2)(mu(1,3)-NCS)(4). The latter has a cuboidal structure having two (cis-DAniF)(2)Mo(2)(2+) units, [Mo(2)], with four thiocyanate groups bridging two [Mo(2)] units in an end-to-end fashion in which the N and S atoms serve as the bridging units. On the contrary, the structure of the cyanate isomer, [Mo(2)(cis-DAniF)(2)](2)(mu(1,1)-NCO)(4) (2), shows an end-on binding of the cyanate linkers. Various physical measurements of 2 and its oxidized species 2.PF(6) indicate that there is strong electronic communication between the two dimetal cores. For 1, two reversible oxidation processes were observed in the cyclic voltammogram corresponding to the successive oxidation to 1(+) and an uncommon 1(2+) species that has a triple-bonded Mo(2)(6+) core. DFT calculations indicate that the antibonding character between the Mo-Mo delta orbitals and thiocyanate p orbitals plays a very important role in elevating the HOMO delta orbital energy that allows formation of the dication. A selenium isomer of 3 was also studied. In both the thiocyanate and selenocyanate bridged dimers of dimers, in which the pseudohalide bridges bind the two dimetal units in an end-to-end fashion, long separations between the dimetal units are observed, and these generate very weak electronic interactions.

High Level Expression of Functional Human IgMs in Human PER.C6 Cells

MAbs. Mar-Apr, 2009  |  Pubmed ID: 20061826

Natural IgM antibodies play an important role in the body's defense mechanisms against transformed cells in the human body and are currently being exploited both in prognoses of malignant lesions and in the therapy of cancer patients. However, despite growing interest and clinical promise, thus far the IgM class of antibodies has failed to gain widespread commercial interest as these are considered to be difficult to produce recombinantly. IgMs are polymeric and have a relatively large mass. In addition, IgM molecules are heavily glycosylated and, when produced in non-human cell lines, they may contain non-human glycan structures which may be potentially immunogenic. Clearly, production systems capable of expressing human recombinant IgM antibodies are needed. We have successfully used PER.C6 cells-a human cell line-to generate three separate human recombinant monoclonal IgMs in suspension cultures in protein-free medium. All three of the IgMs were constructed with joining (J) chain and were expressed in the pentameric form. One of the IgMs was also expressed as a hexamer without J chain. Clones with cell specific productivities greater than 20 pg/cell/day were generated, which led to yields of 0.5 g/L to 2g/L in fed-batch production. All the IgMs expressed were biologically active as shown in binding and cytotoxicity assays. These studies demonstrate the potential of PER.C6 cells for the production of high levels of functional recombinant IgM and other polymeric molecules, using a straightforward and rapid stable cell line generation method.

[Effectiveness of Cytology-based Cervical Cancer Screening in the Colombian Health System]

Biomédica : Revista Del Instituto Nacional De Salud. Sep, 2009  |  Pubmed ID: 20436987

Despite the implementation of cytological screening since 1991, cervical cancer continuous to be the leading cause of cancer mortality among Colombian women.

[Characterization of Malaria Mortality in Valle Del Cauca, 2005-2006]

Biomédica : Revista Del Instituto Nacional De Salud. Dec, 2009  |  Pubmed ID: 20440457

Valle del Cauca is one of the states in Colombia that reports a high number of deaths due to malaria. Understanding the basis of malarial deaths is useful for assessing the efficacy of the health system and to identify areas where improvements are necessary to decrease malaria mortality.

Evidence of Disruption of Conjugation Involving Delta Bonds in Intramolecular Electronic Coupling

Inorganic Chemistry. Dec, 2009  |  Pubmed ID: 19911818

A dimer of dimers containing two quadruply bonded [Mo(2)(DAniF)(3)](+) units (DAniF = N,N'-di(p-anisyl)formamidinate) linked by the S-donor linker, dimethyldithiooxamidate was synthesized, structurally characterized, and electronic communication was probed. The core of [Mo(2)(DAniF)(3)](2)(C(2)S(2)N(2)Me(2)), 1, formed by the Mo(2)NSC(2)SNMo(2) atoms shows two fused but non planar six-membered rings, which differs from that of the beta form of dimethyloxamidate analogue that has a heteronaphthalene-type structure (Cotton, F. A.; Liu, C. Y.; Murillo, C. A.; Villagran, D.; Wang, X. J. Am. Chem. Soc. 2004, 126, 14822). For these two analogous compounds electronic coupling between the two [Mo(2)] units, as determined by electrochemical measurements, diminishes considerably upon replacement of O-donor by S-donor atoms (DeltaE(1/2) = 531 mV and 440 mV, respectively). This suggests that the non planar conformation of the linker in 1 hampers a pathway leading to pi conjugation. Density functional theory (DFT) calculations show that the highest occupied molecular orbitals HOMO-HOMO-1 energy gap of 0.12 eV for 1 is much smaller than that of 0.61 eV for the O-donor analogue, which is consistent with the electrochemical data.

Dietary Selenium Plus Folic Acid As an Antioxidant Therapy for Ethanol-exposed Pups

Birth Defects Research. Part B, Developmental and Reproductive Toxicology. Dec, 2009  |  Pubmed ID: 19918952

Nutrients such as folic acid and selenium are decreased in dams exposed to ethanol during gestation and lactation, affecting their metabolism, antioxidant balance, and the future health of their progeny. We will study whether the supplementation of the maternal diet with folate and selenium can prevent ethanol-induced oxidative liver disorders in the offspring.

Osteonecrosis of the Jaws by Intravenous Bisphosphonates and Osteoradionecrosis: a Comparative Study

Medicina Oral, Patología Oral Y Cirugía Bucal. Dec, 2009  |  Pubmed ID: 19949369

We analyze the possible clinical differences between bone jaw exposed areas in ONJ (osteonecrosis of the jaws) and ORN (osteoradionecrosis).

HPV Prevalence in Colombian Women with Cervical Cancer: Implications for Vaccination in a Developing Country

Infectious Diseases in Obstetrics and Gynecology. 2009  |  Pubmed ID: 20052389

Human Papillomavirus (HPV) vaccines have been considered potentially cost-effective for the reduction of cervical cancer burden in developing countries; their effectiveness in a public health setting continues to be researched. We conducted an HPV prevalence survey among Colombian women with invasive cancer. Paraffin-embedded biopsies were obtained from one high-risk and one low-middle-risk regions. GP5+/GP6+ L1 primers, RLB assays, and E7 type specific PCR were used for HPV-DNA detection. 217 cases were analyzed with 97.7% HPV detection rate. HPV-16/18 prevalence was 63.1%; HPV-18 had lower occurrence in the high-risk population (13.8% versus 9.6%) allowing for the participation of less common HPV types; HPV-45 was present mainly in women under 50 and age-specific HPV type prevalence revealed significant differences. Multiple high-risk infections appeared in 16.6% of cases and represent a chance of replacement. Age-specific HPV prevalence and multiple high-risk infections might influence vaccine impact. Both factors highlight the role of HPVs other than 16/18, which should be considered in cost-effectiveness analyses for potential vaccine impact.

Reduction of Spasticity with Repetitive Transcranial Magnetic Stimulation in Patients with Spinal Cord Injury

Neurorehabilitation and Neural Repair. Jun, 2010  |  Pubmed ID: 20053952

Spasticity with increased tone and spasms is frequent in patients after spinal cord injury (SCI). Damage to descending corticospinal pathways that normally exert spinal segmental control is thought to play an important causal role in spasticity. The authors examined whether the modulation of excitability of the primary motor cortex with high-frequency repetitive transcranial magnetic stimulation (rTMS) could modify lower limb spasticity in patients with incomplete SCI.

A Bacterial Antirepressor with SH3 Domain Topology Mimics Operator DNA in Sequestering the Repressor DNA Recognition Helix

Nucleic Acids Research. Aug, 2010  |  Pubmed ID: 20410074

Direct targeting of critical DNA-binding elements of a repressor by its cognate antirepressor is an effective means to sequester the repressor and remove a transcription initiation block. Structural descriptions for this, though often proposed for bacterial and phage repressor-antirepressor systems, are unavailable. Here, we describe the structural and functional basis of how the Myxococcus xanthus CarS antirepressor recognizes and neutralizes its cognate repressors to turn on a photo-inducible promoter. CarA and CarH repress the carB operon in the dark. CarS, produced in the light, physically interacts with the MerR-type winged-helix DNA-binding domain of these repressors leading to activation of carB. The NMR structure of CarS1, a functional CarS variant, reveals a five-stranded, antiparallel beta-sheet fold resembling SH3 domains, protein-protein interaction modules prevalent in eukaryotes but rare in prokaryotes. NMR studies and analysis of site-directed mutants in vivo and in vitro unveil a solvent-exposed hydrophobic pocket lined by acidic residues in CarS, where the CarA DNA recognition helix docks with high affinity in an atypical ligand-recognition mode for SH3 domains. Our findings uncover an unprecedented use of the SH3 domain-like fold for protein-protein recognition whereby an antirepressor mimics operator DNA in sequestering the repressor DNA recognition helix to activate transcription.

Transmitted Drug Resistance and Type of Infection in Newly Diagnosed HIV-1 Individuals in Honduras

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. Dec, 2010  |  Pubmed ID: 20417152

Transmitted drug resistance (TDR) reduces the efficacy of antiretroviral treatment and is a public health concern.

Inhibition of P38 MAPK Improves Intestinal Disturbances and Oxidative Stress Induced in a Rabbit Endotoxemia Model

Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society. May, 2010  |  Pubmed ID: 20003078

Lipopolysaccharide (LPS) decreases intestinal contractility and induces the release of reactive oxygen species, which play an important role in the pathogenesis of sepsis. p38 mitogen-activated protein kinase (MAPK) can be activated by a variety of stimuli such as LPS. The aims of this study were: (i) to investigate the role of p38 MAPK in the effect of LPS on (a) the acetylcholine, prostaglandin E(2) and KCl-induced contractions of rabbit duodenum and (b) the oxidative stress status; (ii) to localize the active form of p38 in the intestine.

Sharing Kidneys Across Donor-service Area Boundaries with Sensitized Candidates Can Be Influenced by HLA C

Clinical Transplantation. Jan-Feb, 2010  |  Pubmed ID: 20015269

The United Network for Organ Sharing (UNOS) implemented the virtual crossmatch system in UNet as a way to improve the likelihood of a negative crossmatch when kidneys are shared with HLA-sensitized candidates across donor service area (DSA) boundaries. The role of HLA C in that process is not universally appreciated. We recently experienced an unexpected positive flow T and B cell crossmatch for an imported, HLA zero-mismatched kidney because of donor-specific HLA C antibodies and transplanted it into the backup candidate. HLA C locus antigens were not typed by the OPO's laboratory that sent the kidney so the UNet virtual crossmatch could not "strike" our candidate from the UNOS match run. HLA C locus typing data of donors for kidneys our DSA imported from other DSAs revealed that C typing was not performed in 23% (14/60) and was discrepant with our molecular type for 10% (6/60) and was concordant in 67% (40/60) of cases. The rate of positive donor-specific crossmatches was higher (83%) for HLA C discrepantly typed donors than for concordantly typed donors (44%). Sensitization for HLA C (42%) is less frequent than for A (80%) or B (83%) locus antigens but the immunogenicity of C locus antigens in patients who make C locus antibodies is equivalent in black and white patients. Finally, the transplant rate of imported kidneys into class I-sensitized candidates was 24%, and C locus-sensitized candidates comprised 55% of those transplanted.

Proof by EPR Spectroscopy That the Unpaired Electron in an Os(2)(7+) Species is in a Delta* Metal-based Molecular Orbital

Inorganic Chemistry. Jan, 2010  |  Pubmed ID: 19947645

Variable temperature structural and EPR studies are reported on the paddlewheel compound [Os(2)(hpp)(4)Cl(2)]PF(6), 1, (hpp = the anion of the bicyclic guanidine 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) that contains a rare M(2)(7+) species, with the goal of determining whether the unpaired electron resides in a metal- or ligand-based molecular orbital. Crystallographic studies show that the Os-Os distance in 1 remains essentially unchanged from 213 to 30 K, which is consistent with no changes in electronic structure in this range of temperature. It is noteworthy that the metal-metal distance in 1 is about 0.05 A shorter than that in the precursor Os(2)(hpp)(4)Cl(2), which is consistent with the loss of an electron in a delta* orbital. EPR spectra of 1 were measured in dilute frozen solution, powder, and single crystals. The spectra were observable only below about 50 K, with an exceptionally large line width, approximately 3,750 gauss, for a powdered sample, due to dipolar interactions and to short relaxation times. There is a very small average g value of approximately 0.750 and a cylindrical symmetry about the Os-Os bond. These data are consistent with the unpaired electron orbital having a large L value, such as that of a delta* orbital. The combination of X-ray structural data, the short relaxation time, and the magnetic data provide strong evidence that the unpaired electron in this nine-electron Os(2)(7+) species is localized in a metal-based orbital with this electron residing predominantly in a delta* orbital rather than in a pi* orbital and, thus, having an electronic configuration of sigma(2)pi(4)delta(2)delta*.

Large Variation in Detection of Histidine-rich Protein 2 in Plasmodium Falciparum Isolates from Colombia

The American Journal of Tropical Medicine and Hygiene. Oct, 2010  |  Pubmed ID: 20889875

Most rapid diagnostic tests (RDTs) available use histidine-rich protein 2 (HRP2) as a target. However, it has been reported that sequence variations of this protein affects its sensitivity. Currently, there is insufficient evidence for HRP2 variability in Plasmodium falciparum isolates from Colombia and its relationship with RDT performance. To determine possible geographic differences and their effects on the performance of RDTs, 22 blood samples from patients with P. falciparum malaria from Tumaco and Buenaventura, Colombia were assessed by measurement of HRP2 concentration by an HRP2 enzyme-linked immunosorbent assay, RDTs, and thick blood smear. Statistical analysis showed an association between RDT performance and HRP2 concentrations. No significant difference was found between locations. A large variation of antigen concentration in samples was found at same parasitemia. In contrast to previously reports, there was no correlation between initial parasitemia and HRP2 concentration. Our results indicate that antigen quantity should be studied more carefully because the sensitivity of the RDT is affected more by antigen concentration than by parasitemia.

[Quality of Vaginal Smear for Cervical Cancer Screening: a Concordance Study]

Biomédica : Revista Del Instituto Nacional De Salud. Jan-Mar, 2010  |  Pubmed ID: 20890555

Cervical cancer is the leading cause of cancer deaths in the female population in Colombia. The low impact of Papanicolaou smears in reducing cervical cancer mortality in some countries has been attributed to their low reproducibility and high rates of false negatives.

Efficacy of Usual and High Doses of Daptomycin in Combination with Rifampin Versus Alternative Therapies in Experimental Foreign-body Infection by Methicillin-resistant Staphylococcus Aureus

Antimicrobial Agents and Chemotherapy. Dec, 2010  |  Pubmed ID: 20921321

The treatment of prosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to be a challenge for the clinician. The aim of this study was to evaluate the efficacies of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg of body weight/day, respectively, in humans) and in combination with rifampin and to compare the activities to those of conventional anti-MRSA therapies. We used MRSA strain HUSA 304, with the following MICs and minimal bactericidal concentrations (MBCs), respectively: daptomycin, 1 μg/ml and 4 μg/ml; vancomycin, 2 μg/ml and 4 μg/ml; linezolid, 2 μg/ml and >32 μg/ml; and rifampin, 0.03 μg/ml and 0.5 μg/ml. In time-kill curves, only daptomycin and its combinations with rifampin achieved a bactericidal effect in log and stationary phases. For in vivo studies, we used a rat foreign-body infection model. Therapy was administered for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin at 25 mg/kg/12 h, and linezolid at 35 mg/kg/12 h, and each antibiotic was also combined with rifampin. Among monotherapies, daptomycin at 100 mg/kg/day and rifampin performed better than vancomycin and linezolid. In combination with rifampin, both dosages of daptomycin were significantly better than all other combinations, but daptomycin at 100 mg/kg/day plus rifampin achieved better cure rates at day 11 (P < 0.05) than daptomycin at 45 mg/kg/day plus rifampin. Resistant strains were found in monotherapies with rifampin and daptomycin at 45 mg/kg/day. In conclusion, daptomycin at high doses was the most effective monotherapy and also improved the efficacy of the combination with rifampin against foreign-body infections by MRSA. Clinical studies should confirm whether this combination may be considered the first-line treatment for foreign-body infections by MRSA in humans.

Snail1 Suppresses TGF-beta-induced Apoptosis and is Sufficient to Trigger EMT in Hepatocytes

Journal of Cell Science. Oct, 2010  |  Pubmed ID: 20930141

Although TGF-β suppresses early stages of tumour development, it later contributes to tumour progression when cells become resistant to its suppressive effects. In addition to circumventing TGF-β-induced growth arrest and apoptosis, malignant tumour cells become capable of undergoing epithelial-to-mesenchymal transition (EMT), favouring invasion and metastasis. Therefore, defining the mechanisms that allow cancer cells to escape from the suppressive effects of TGF-β is fundamental to understand tumour progression and to design specific therapies. Here, we have examined the role of Snail1 as a suppressor of TGF-β-induced apoptosis in murine non-transformed hepatocytes, rat and human hepatocarcinoma cell lines and transgenic mice. We show that Snail1 confers resistance to TGF-β-induced cell death and that it is sufficient to induce EMT in adult hepatocytes, cells otherwise refractory to this transition upon exposure to TGF-β. Furthermore, we show that Snail1 silencing prevents EMT and restores the cell death response induced by TGF-β. As Snail1 is a known target of TGF-β signalling, our data indicate that Snail1 might transduce the tumour-promoting effects of TGF-β, namely the EMT concomitant with the resistance to cell death.

Folic Acid and Selenite During Reproduction, Gestation and Lactation Protect Against Ethanol Changed Se Bioavailability

Alcohol and Alcoholism (Oxford, Oxfordshire). Nov-Dec, 2010  |  Pubmed ID: 20977997

Levels of antioxidants such as folic acid and selenium decrease in dams exposed to ethanol during gestation and lactation, affecting their antioxidant status, their reproductive function and consequently the health of their progeny. We will study whether a Se (0.5 p.p.m.) plus folic acid (8 p.p.m.) supplemented diet administered to ethanol-exposed dams and male rats prevents the effects provoked by ethanol in Se bioavailability and in their glutathione peroxidase (GPx) activity, thus improving the health of their offspring.

Bone Resorptive Activity of Osteoclast-like Cells Generated in Vitro by PEG-induced Macrophage Fusion

Biological Research. 2010  |  Pubmed ID: 21031266

Normal bone remodeling is maintained by a balance between osteoclast and osteoblast activity, whereas defects in osteoclast activity affecting such balance result in metabolic bone disease. Macrophage-macrophage fusion leading to multinucleated osteoclasts being formed is still not well understood. Here we present PEG-induced fusion of macrophages from both U937/A and J774 cell lines and the induced differentiation and activation of osteoclast-like cells according to the expression of osteoclast markers such as tartrate resistant acid phosphatase (TRAP) and bone resorptive activity. PEG-induced macrophage fusion, during the non-confluent stage, significantly increased the osteoclastogenic activity of macrophages from cell lines compared to that of spontaneous cell fusion in the absence of PEG (polyethylene glycol). The results shown in this work provide evidence that cell fusion per se induces osteoclast-like activity. PEG-fused macrophage differential response to pretreatment with osteoclastogenic factors was also examined in terms of its ability to form TRAP positive multinucleated cells (TPMNC) and its resorptive activity on bovine cortical bone slices. Our work has also led to a relatively simple method regarding those previously reported involving cell co-cultures. Multinucleated osteoclast-like cells obtained by PEG-induced fusion of macrophages from cell lines could represent a suitable system for conducting biochemical studies related to basic macrophage fusion mechanisms, bone-resorption activity and the experimental search for bone disease therapeutic alternatives.

Catechin Derivatives from Parapiptadenia Rigida with in Vitro Wound-healing Properties

Journal of Natural Products. Dec, 2010  |  Pubmed ID: 21080642

Analysis of the ethanolic extract of the bark from Parapiptadenia rigida resulted in the isolation of the new catechin derivatives 4',3''-di-O-methylapocynin-D (10), 4',3''-di-O-methylapocynin-B (11), epigallocatechin-3-O-ferulate (8), and 4'-O-methylepigallocatechin-3-O-ferulate (9) and the catechins 4'-O-methylepigallocatechin-3-O-gallate (6) and 4'-O-methylepicatechin-3-O-gallate (7). These compounds, isolated for the first time from a natural source, are accompanied by the five known catechins 4'-O-methylgallocatechin (1), 4'-O-methylepigallocatechin (2), 3'-O-methylepicatechin (3), epigallocatechin-3-O-gallate (4), and epicatechin-3-O-gallate (5). Compounds 5 and 7 displayed promising wound-healing effects in a scratch assay. Some of the catechin derivatives showed inhibitory effects on NF-κB DNA binding and p38α MAPK activity.

Carotenoid Composition and Antioxidant Activity of the Raw and Boiled Fruit Mesocarp of Six Varieties of Bactris Gasipaes

Archivos Latinoamericanos De Nutrición. Mar, 2010  |  Pubmed ID: 21090177

Total carotenoid content and composition of carotenoids of six varieties of Bactris gasipaes were determined by spectrophotometry and HPLC, with photodiode array detector. Significant differences in total carotenoid content (1.1 to 22.3 mg/100g) were detected among these varieties. Boiling the fruits for 30 minutes did not affect total carotenoid content, but did change the amount of some specific carotenoids, mainly by the production of Z-isomers. Peach palm varieties had the same carotenoids, but in different proportions, presenting mainly, all E-beta-carotene (26.2% to 47.9%), Z-gamma-carotene (18.2% to 34.3%) and Z-lycopene (10.2% to 26.8%). When antioxidant activity was evaluated using DPPH, it was observed that the variety with higher percentages of beta-carotene (54.1%) presented the higher activity. This is one of the first reports in carotenoid content and antioxidant activity in well typified varieties of Bactris gasipaes, whose results could have a positive impact in the consumption of certain peach palm varieties.

One Year Follow-up in a Group of Half-marathon Runners with Type-1 Diabetes Treated with Insulin Analogues

The Journal of Sports Medicine and Physical Fitness. Dec, 2010  |  Pubmed ID: 21178938

The objective was to describe the strategies that type-1 diabetic runners treated with insulin analogues apply in a half-marathon race and the changes after a year of experience participating in long-distance athletic competitions.

[New Paradigms and Challenges in Cervical Cancer Prevention and Control in Latin America]

Salud Pública De México. Nov-Dec, 2010  |  Pubmed ID: 21271014

Cervical cancer continues to be a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had almost no major impact on reducing cervical cancer incidence and mortality rates, which are still high in the region. The availability of new screening tools to detect precancerous lesions provide great opportunities for cervical cancer prevention in the region, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. This paper summarizes the scientific evidence and regional experiences related to: i) the use of HPV testing and visual inspection after the application of acetic acid (VIA) in primary screening and ii) the implementation of adolescent HPV vaccination programs. Finally, we outline a number of recommendations for different resource settings. The feasibility of implementing successful and sustainable national cervical cancer prevention programs in Latin American countries in the region will depend on health priorities and the availability of infrastructure and health personnel--as determined by rigorous local situational analysis.

Bortezomib As Rescue Therapy for Antibody Mediated Rejection: a Single-center Experience

Clinical Transplants. 2010  |  Pubmed ID: 21696060

Case series have reported the use of bortezomib for treatment of primary and refractory treatment of cell-mediated acute rejection. The purpose of this article is to review a single-center experience with bortezomib used to treat humoral rejection in four transplant recipients. All patients received bortezomib after suffering antibody-mediated rejection refractory to intravenous immunoglobulin and plasmapheresis. Each patient had improved renal function after bortezomib treatment, biopsies became c4d negative in three of the four patients and the level of donor specific antibody reduction was mixed. Adverse drug events were not encountered, although two patients suffered infections, H1N1 pneumonia and cytomegalovirus colitis. In conclusion, these four cases demonstrate the promising use of bortezomib as rescue therapy for antibody mediated rejection. Future research is needed to explore the impact of bortezomib on HLA removal, histological reversal of rejection, and long-term graft function after transplantation.

[Microbiological and Chemical Quality of Water Used in Colombian Food Industries]

Biomédica : Revista Del Instituto Nacional De Salud. Jul-Sep, 2010  |  Pubmed ID: 21713344

Food safety is a public health concern that is recognized worldwide. Food-borne diseases affect millions of people throughout the world, although mainly in developing countries. The current study was performed within the framework of an inter-administrative agreement in Colombia that considers decisions for improving the sanitary status of products from the agrofood industry in Colombia.

Global Sequence Variation in the Histidine-rich Proteins 2 and 3 of Plasmodium Falciparum: Implications for the Performance of Malaria Rapid Diagnostic Tests

Malaria Journal. 2010  |  Pubmed ID: 20470441

Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region.

Origin and Dissemination Across the Colombian Andes Mountain Range of Sulfadoxine-pyrimethamine Resistance in Plasmodium Falciparum

Antimicrobial Agents and Chemotherapy. Aug, 2010  |  Pubmed ID: 20498318

The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) in treating uncomplicated Plasmodium falciparum malaria is unevenly distributed in Colombia. The Andes mountain range separates regions in the west where malaria is endemic from those in the east and constitutes a barrier against gene flow and the dispersal of parasite populations. The distribution of dhfr and dhps genotypes of 146 P. falciparum samples from the eastern Amazon and Orinoco basins and Northwest and Southwest Pacific regions of Colombia was consistent with the documented levels of therapeutic efficacy of SP. The diversity of four dhfr- and dhps-linked microsatellites indicated that double- and triple-mutant alleles for both resistance loci have a single origin. Likewise, multilocus association genotypes, including two unlinked microsatellite loci, suggested that genetic exchanges between the eastern Orinoco and Northwest Pacific populations has taken place across the Andes, most probably via migration of infected people.

Predictive Value of Endocervical Curettage at Cervical Conization and Provider Practices in Management of High-grade Cervical Dysplasia

The Journal of Reproductive Medicine. Mar-Apr, 2010  |  Pubmed ID: 20506673

To determine the utility of endocervical curettage (ECC) at cervical conization for predicting residual or recurrent dysplasia and to evaluate differences in management between general gynecologists and gynecologic oncologists.

Different Effects on Zinc Redistribution if Ethanol is Consumed Before or Immediately After Birth

Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS). Jul, 2010  |  Pubmed ID: 20507833

The effect of ethanol consumption, either during pregnancy and/or lactation, on the altered metabolism of zinc (Zn) is not well-defined. Therefore, this study was performed to analyse the effect of chronic ethanol exposure on Zn redistribution in dams and offspring during either gestation and/or lactation.

Waste Tyre Pyrolysis: Modelling of a Moving Bed Reactor

Waste Management (New York, N.Y.). Dec, 2010  |  Pubmed ID: 20510597

This paper describes the development of a new model for waste tyre pyrolysis in a moving bed reactor. This model comprises three different sub-models: a kinetic sub-model that predicts solid conversion in terms of reaction time and temperature, a heat transfer sub-model that calculates the temperature profile inside the particle and the energy flux from the surroundings to the tyre particles and, finally, a hydrodynamic model that predicts the solid flow pattern inside the reactor. These three sub-models have been integrated in order to develop a comprehensive reactor model. Experimental results were obtained in a continuous moving bed reactor and used to validate model predictions, with good approximation achieved between the experimental and simulated results. In addition, a parametric study of the model was carried out, which showed that tyre particle heating is clearly faster than average particle residence time inside the reactor. Therefore, this fast particle heating together with fast reaction kinetics enables total solid conversion to be achieved in this system in accordance with the predictive model.

Body Composition After Endogenous (Cushing's Syndrome) and Exogenous (rheumatoid Arthritis) Exposure to Glucocorticoids

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme. Jul, 2010  |  Pubmed ID: 20514604

Exposure to chronic glucocorticoid (GC) excess determines changes in body composition. The aim of the study was to compare body composition in women exposed to endogenous hypercortisolism (Cushing's syndrome, CS), exogenous glucocorticoid treatment (rheumatoid arthritis, RA) and controls. Fifty-one CS women, 26 RA women treated with low-dose prednisone (5 mg/day or 10 mg/2 days), and 78 female controls were included. Fourteen CS patients were hypercortisolemic, 37 in remission (10 required hydrocortisone substitution after surgery). Body composition parameters were measured by dual-energy X-ray absorptiometry scanning (DEXA). RA patients had a greater waist-hip ratio (WHR) (p<0.01), less lean body mass (LBM) (p<0.01), and lumbar bone mineral density (BMD) (p<0.01) than controls. CS patients, globally and those with cured disease, had more total fat (both percentage and kg) and trunk fat percentage, and less whole body-BMD than RA patients (p<0.05, p<0.01, p<0.05, respectively). Active CS patients had less whole body-BMD and more LBM than RA patients (p<0.05, p=0.01, respectively). Cured CS patients not taking hydrocortisone had more total fat [both percentage (p<0.05) and kg (p<0.05)], trunk fat percentage (p<0.05), lumbar BMD (p<0.01) than RA patients. Cured CS patients requiring hydrocortisone only differed from RA patients by smaller WHR (p<0.01). All the differences in BMD disappeared when the data were reanalyzed including only the estrogen-deficient groups. Hypercortisoliof CS determines an irreversible increase in body fat, greater than in RA. Endogenous and exogenous exposure to GC negatively affects body composition by increasing the WHR. There appears to be no additional effect on BMD in estrogen-deficient women.

Koch's Triangle and the Atrioventricular Node in Ebstein's Anomaly: Implications for Catheter Ablation

Revista Española De Cardiología. Jun, 2010  |  Pubmed ID: 20515623

The development of ablation techniques for supraventricular arrhythmias in patients with Ebstein's anomaly have led to a need for better understanding of the morphology of the triangle of Koch and the position of the atrioventricular (AV) node in this structure.

Optimal Atrioventricular Delay in CRT Patients Can Be Approximated Using Surface Electrocardiography and Device Electrograms

Journal of Cardiovascular Electrophysiology. Nov, 2010  |  Pubmed ID: 20522154

Electrocardiographic AV Delay Adjustment.

Functions of Genes and Enzymes Involved in Phenalinolactone Biosynthesis

Chembiochem : a European Journal of Chemical Biology. Jul, 2010  |  Pubmed ID: 20540056

Phenalinolactones are novel terpene glycoside antibiotics produced by Streptomyces sp. Tü6071. Inactivation of three oxygenase genes (plaO2, plaO3 and plaO5), two dehydrogenase genes (plaU, plaZ) and one putative acetyltransferase gene (plaV) led to the production of novel phenalinolactone derivatives (PL HS6, PL HS7, PL HS2 and PL X1). Furthermore, the exact biosynthetic functions of two enzymes were determined, and their in vitro activities were demonstrated. PlaO1, an Fe(II)/alpha-ketoglutarate-dependent dioxygenase, is responsible for the key step in gamma-butyrolactone formation, whereas PlaO5, a cytochrome P450-dependent monooxygenase, catalyses the 1-C-hydroxylation of phenalinolactone D. In addition, stable isotope feeding experiments with biosynthetic precursors shed light on the origin of the carbons in the gamma-butyrolactone moiety.

The Regulatory Action of the Myxobacterial CarD/CarG Complex: a Bacterial Enhanceosome?

FEMS Microbiology Reviews. Sep, 2010  |  Pubmed ID: 20561058

A global regulatory complex made up of two unconventional transcriptional factors, CarD and CarG, is implicated in the control of various processes in Myxococcus xanthus, a Gram-negative bacterium that serves as a prokaryotic model system for multicellular development and the response to blue light. CarD has a unique two-domain architecture composed of: (1) a C-terminal DNA-binding domain that resembles eukaryotic high mobility group A (HMGA) proteins, which are relatively abundant, nonhistone components of chromatin that remodel DNA and prime it for the assembly of multiprotein-DNA complexes essential for various DNA transactions, and (2) an N-terminal domain involved in interactions with CarG and RNA polymerase, which is also the founding member of the large CarD_TRCF family of bacterial proteins. CarG, which does not bind DNA directly, has a zinc-binding motif of the type found in the archaemetzincin class of metalloproteases that, in CarG, appears to play a purely structural role. This review aims to provide an overview of the known molecular details and insights emerging from the study of the singular CarD-CarG prokaryotic regulatory complex and its parallels with enhanceosomes, the higher order, nucleoprotein transcription complexes in eukaryotes.

Protection Against Cellular Stress by 25-hydroxyvitamin D3 in Breast Epithelial Cells

Journal of Cellular Biochemistry. Aug, 2010  |  Pubmed ID: 20564226

25-Hydroxyvitamin D(3) (25(OH)D(3)) is a prohormone and a major vitamin D metabolite. The discovery of (25(OH)D(3)) 1 alpha-hydroxylase in many vitamin D target organs has yielded an increased interest in defining the role(s) of 25(OH)D(3) in these tissues. The etiology of cancer appears to be complex and multi-factorial. Cellular stress (e.g., DNA damage, hypoxia, oncogene activation) has been identified as one of the key factors responsible for initiating the carcinogenesis process. In this study, we investigated whether 25(OH)D(3) protects breast epithelial cells from cellular stress using an established breast epithelial cell line MCF12F. To better elucidate the role of 25(OH)D(3) in the stress response, we used multiple in vitro stress models including serum starvation, hypoxia, oxidative stress, and apoptosis induction. Under all these stress conditions, 25(OH)D(3) (250 nmol/L) treatment significantly protected cells against cell death. Low-serum stress induced p53 expression accompanied with downregulation of PCNA, the presence of 25(OH)D(3) consistently inhibited the alteration of p53 and PCNA, suggesting that these molecules were involved in the stress process and may be potential target genes of 25(OH)D(3). miRNA microarray analysis demonstrated that stress induced by serum starvation caused significant alteration in the expression of multiple miRNAs including miR182, but the presence of 25(OH)D(3) effectively reversed this alteration. These data suggest that there is a significant protective role for 25(OH)D(3) against cellular stress in the breast epithelial cells and these effects may be mediated by altered miRNA expression.

[Antiplatelet Treatment for Secondary Prevention of Ischemic Stroke or Transient Ischemic Attack]

Revista De Investigación Clínica; Organo Del Hospital De Enfermedades De La Nutrición. Mar-Apr, 2010  |  Pubmed ID: 20597393

[Antiocoagulation for the Secondary Prevention of Ischemic Stroke]

Revista De Investigación Clínica; Organo Del Hospital De Enfermedades De La Nutrición. Mar-Apr, 2010  |  Pubmed ID: 20597394

[Statins for the Secondary Prevention of Ischemic Stroke]

Revista De Investigación Clínica; Organo Del Hospital De Enfermedades De La Nutrición. Mar-Apr, 2010  |  Pubmed ID: 20597396

[Lifestye and Primary and Secondary Prevention for Cerebrovascular Disease]

Revista De Investigación Clínica; Organo Del Hospital De Enfermedades De La Nutrición. Mar-Apr, 2010  |  Pubmed ID: 20597398

CYP2W1 Variant Alleles in Caucasians and Association of the CYP2W1 G541A (Ala181Thr) Polymorphism with Increased Colorectal Cancer Risk

Pharmacogenomics. Jul, 2010  |  Pubmed ID: 20602611

To detect differences in the frequency of the known nonsynonymous CYP2W1 polymorphisms between colorectal cancer patients and healthy subjects.

Role of Potassium Channels in Rabbit Intestinal Motility Disorders Induced by 2, 2'-azobis (2-amidinopropane) Dihydrochloride (AAPH)

Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society. Jun, 2010  |  Pubmed ID: 20610857

Oxidative stress appears to play a role in the pathogenesis of several inflammatory gastrointestinal diseases. Changes in intestinal motility have been reported in different models of intestinal inflammation. The initiating factor of altered motility could be an alteration of gut redox status. The aim of this study was to investigate the effect of oxidative stress evoked by 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH) on the intestinal motility of rabbit duodenum and the possible contribution of different K(+) channels in mediating this response. Whole thickness segments of rabbit duodenum were suspended in the direction of the longitudinal or circular smooth muscle fibres in an organ bath to study the effects of AAPH alone, or in the presence of different K(+) channel blockers on the amplitude, frequency and tone of spontaneous contractions. In circular muscle, AAPH 20 mM induced a reduction of the amplitude, the frequency and tone of the spontaneous contractions. In longitudinal muscle, AAPH 10 mM induced a reduction of the amplitude and tone of the spontaneous contractions. The reduction of the amplitude and tone induced by AAPH was reverted by BaCl2 (1 mM) and TEA (5 mM). Charybdotoxin (100 nM) and iberiotoxin (100 nM) only reverted the reduction of the tone induced by AAPH. In conclusion, our results show that the peroxyl radicals released by AAPH reduced the amplitude and the tone of the spontaneous contractions of the longitudinal smooth muscle from rabbit small intestine. Inward rectifier and intermediate and large-conductance Ca(2+)-activated K(+) channels could be involved in these effects.

Obstructive Sleep Apnea and Immunity: Relationship of Lymphocyte Count and Apnea Hypopnea Index

Southern Medical Journal. Aug, 2010  |  Pubmed ID: 20622723

The impact of chronic poor quality sleep on immunity as seen in obstructive sleep apnea (OSA) has not been evaluated. We aim to explore the relationship between lymphocytes, neutrophil, and total leukocyte counts with severity stratified apnea hypopnea index (AHI) in patients with OSA.

[Following-up Females Having an Abnormal Pap Smear in Colombia]

Revista De Salud Pública (Bogotá, Colombia). Feb, 2010  |  Pubmed ID: 20628695

Evaluating the opportunity and access to diagnosis and treatment for females having had an abnormal Pap smear (high-grade epithelial lesion and cervical cancer) in Colombia from June 2005 to June 2006.

Insights into the Structure and Stability of the Carbonic Acid Dimer

Physical Chemistry Chemical Physics : PCCP. Sep, 2010  |  Pubmed ID: 20640250

In this paper we report the geometries and properties of 40 structural isomers located on the MP2/6-311++G** PES of the carbonic acid dimer. All six possible combinations of carbonic acid monomers were considered. The dimers are divided into six geometrical motifs. Our data suggests that combinations of anti-anti monomers do not necessarily lead to larger stabilization energies in the formation of the dimers. MP2 underestimates the relative binding energies with respect to CCSD(T) by as much as 3.2 kcal mol(-1). At least 3 different dimers which may contribute to the stability of carbonic acid are predicted to have significant populations. Binding energy is only directly related to relative stability when comparing dimers formed from the same monomers. Overall stabilization is mainly dictated by attractive electrostatic interactions via cooperative polarization by virtue of the spatial arrangement of the dipole moment components along the polar bonds. Shorter OH bond distances and larger bond orders predicted for the hydrogen bonds directed towards carbonyl groups make for stronger hydrogen bonding than in O...H bonds directed towards hydroxyl groups.

Reassessment of the Toxin Profile of Cylindrospermopsis Raciborskii T3 and Function of Putative Sulfotransferases in Synthesis of Sulfated and Sulfonated PSP Toxins

Toxicon : Official Journal of the International Society on Toxinology. Dec, 2010  |  Pubmed ID: 20692275

The toxigenic freshwater cyanobacterium Cylindrospermopsis raciborskii T3 has been used as a model to study and elucidate the biosynthetic pathway of tetrahydropurine neurotoxins associated with paralytic shellfish poisoning (PSP). There are nevertheless several inconsistencies and contradictions in the toxin profile of this strain as published by different research groups, and claimed to include carbamoyl (STX, NEO, GTX2/3), decarbamoyl (dcSTX), and N-sulfocarbamoyl (C1/2, B1) derivatives. Our analysis of the complete genome of another PSP toxin-producing cyanobacterium, Raphidiopsis brookii D9, which is closely related to C. raciborskii T3, resolved many issues regarding the correlation between biosynthetic pathways, corresponding genes and the T3 toxin profile. The putative sxt gene cluster in R. brookii D9 has a high synteny with the T3 sxt cluster, with 100% nucleotide identity among the shared genes. We also compared the PSP toxin profile of the strains by liquid chromatography coupled to mass spectrometry (LC-MS/MS). In contrast to published reports, our reassessment of the PSP toxin profile of T3 confirmed production of only STX, NEO and dcNEO. We gained significant insights via correlation between specific sxt genes and their role in PSP toxin synthesis in both D9 and T3 strains. In particular, analysis of sulfotransferase functions for SxtN (N-sulfotransferase) and SxtSUL (O-sulfotransferase) enzymes allowed us to propose an extension of the PSP toxin biosynthetic pathway from STX to the production of the derivatives GTX2/3, C1/2 and B1. This is a significantly revised view of the genetic mechanisms underlying synthesis of sulfated and sulfonated STX analogues in toxigenic cyanobacteria.

[Circumferences to Evaluate Changes in Body Mass and Amount of Total Fat of Women in Second and Third Trimester of Pregnancy]

Nutrición Hospitalaria : Organo Oficial De La Sociedad Española De Nutrición Parenteral Y Enteral. Jul-Aug, 2010  |  Pubmed ID: 20694305

To evaluate the maternal nutritional state through simple anthropometric indicators as middle-arm circumference (MAC), half thigh (HTC) and calf (CC), to value changes in the body mass and quantity of total fat, in women on second and third pregnancy trimester.

Watermelon Stomach, Hemorrhagic Pericarditis, Small Cell Carcinoma of the Lung and Synchronous Squamous Cell Carcinoma of the Tongue Base

Revista Portuguesa De Pneumologia. Jul-Aug, 2010  |  Pubmed ID: 20700563

Based on a case of gastric antral vascular ectasia (watermelon stomach) that was associated with hemorrhagic pericarditis, small cell lung carcinoma with mediastinal lymph node metastases and a synchronous squamous cell carcinoma of the base of the tongue, the authors made a review of the clinical, endoscopic and histopathological aspects of this type of gastropathy, and its association with other diseases, and of the results of its endoscopic therapy. The causes of hemorrhagic pericarditis are considered, emphasizing the necessity to know if the effusion has a malignant etiology. To the best of our knowledge the association of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of the base of the tongue has not yet been described. Extensive metastases to mediastal lymph nodes are common to small cell lung carcinoma.

New CO2 Capture Process for Hydrogen Production Combining Ca and Cu Chemical Loops

Environmental Science & Technology. Sep, 2010  |  Pubmed ID: 20704282

This paper presents a new solids looping process for capturing CO2 while generating hydrogen and/or electricity from natural gas. The process is based on the sorption enhanced reforming of CH4, employing CaO as a high temperature CO2 sorbent, combined with a second chemical loop of CuO/Cu. The exothermic reduction of CuO with CH4 is used to obtain the heat necessary for the decomposition of the CaCO3 formed in the reforming step. The main part of the process is completed by the oxidation of Cu to CuO, which is carried out with air diluted with a product gas recycle of this reactor at sufficiently low temperatures and high pressures to avoid the decomposition of a substantial fraction of CaCO3.

Enhanced Induction of Mucin-depleted Foci in Estrogen Receptor {beta} Knockout Mice

Cancer Prevention Research (Philadelphia, Pa.). Sep, 2010  |  Pubmed ID: 20716634

The role of the estrogen receptor beta (ERbeta) in the colon has received considerable interest, yet in vivo models are needed to better define its protective actions. In the present study, wild-type (WT), ERalpha, and ERbeta knockout (alphaERKO and betaERKO) mice were injected with azoxymethane, a colon chemical carcinogen. Fourteen weeks after azoxymethane exposure, the incidence of aberrant crypt foci (ACF) was assessed by methylene blue staining. betaERKO mice showed significantly higher incidence (P < 0.001) of ACF (15.0 +/- 2.5) compared with alphaERKO (3.4 +/- 1.0) and WT (4.6 +/- 1.0) mice. The colons in several betaERKO mice had increased thickness and loss of normal morphology. It has been reported that ERbeta plays a role in the maintenance of the colonic crypt architecture; this may explain the loss of crypt organization in the colonic epithelium of betaERKO mice. The presence of mucin-depleted foci (MDF) has been shown, both in humans and in rodents, as an early event in colon cancer. Therefore, to surpass the limitations with ACF scoring, we performed Alcian blue-neutral red staining to assess the presence of MDF. This assay allowed the assessment of precancerous lesions on all the betaERKO mice colons (38.3 +/- 4.0; P < 0.001), comparing to WT and alphaERKO mice (6.6 +/- 1.5 and 10.0 +/- 1.9, respectively), and served to confirm the ACF results. Together, these data support the use of MDF staining as a biomarker for precancerous lesions and the protective role of ERbeta in colon carcinogenesis.

Erythema Multiforme: Diagnosis, Clinical Manifestations and Treatment in a Retrospective Study of 22 Patients

Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. Nov, 2010  |  Pubmed ID: 20738747

Erythema multiforme (EM) is an acute disorder of the skin and mucosal membranes manifesting in the oral cavity (60-70% of all patients) as polymorphic erosive, ampullar, and bloodstained crusts. The etiology is unclear, although an autoimmune mechanism is involved. Infections and drugs have been implicated in the etiopathogenesis. With the exception of corticosteroids, no specific treatment for EM is available.

Intestinal Effects of Lipopolysaccharide in Rabbit Are Mediated by Cyclooxygenase-2 Through P38 Mitogen Activated Protein Kinase

European Journal of Pharmacology. Dec, 2010  |  Pubmed ID: 20832398

The mediators of the pathophysiological symptoms of septic shock are not completely understood. The intracellular signalling mechanisms of lipopolysaccharide (LPS)-induced effects need further investigation. This study investigates (1) the role of COX-2 in the effect of LPS on (a) the KCl, acetylcholine and prostaglandin E₂-induced contractions of rabbit duodenum and (b) the oxidative stress status in plasma and intestine and (2) the relationship between p38 MAPK and COX-2 expression in rabbit duodenum. Rabbits were injected i.v. with either (1) saline, (2) LPS, (3) SB203580, a p38 MAPK inhibitor, (4) SB203580+LPS, (5) NS-398, a COX-2 inhibitor or (6) NS-398+LPS. Contractility studies were performed by suspending pieces of duodenum in an organ bath in the direction of longitudinal and circular smooth muscle fibres. The formation of products of oxidative damage to proteins (carbonyls) and lipids [malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)] was quantified in intestinal tissue and plasma. The protein expression of COX-2 was measured by western blot. The KCl, acetylcholine and prostaglandin E₂-induced contractions decreased with LPS. In addition, LPS increased the levels of carbonyls and MDA+4-HDA in plasma and duodenum as well as COX-2 expression in duodenal tissue. All these effects were blocked by NS-398. The p38 MAPK inhibitor SB203580 blocked the effect of LPS on COX-2 expression. These results suggest that the effect of LPS on KCl, acetylcholine and prostaglandin E₂-induced contractions in the rabbit duodenum and oxidative stress might be mediated by an increase in COX-2 expression through the p38 MAPK pathway.

The Effect of Left Ventricular Pacing Site on Cardiac Resynchronization Therapy Outcome and Mortality: the Results of a PROSPECT Substudy

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. Dec, 2010  |  Pubmed ID: 20852290

Left ventricular pacing site (LV-PS) was prospectively collected to test the influence of the anatomical LV-PS on the outcome of cardiac resynchronization therapy (CRT) and mortality.

Multielemental Fractionation in Human Peripheral Blood Mononuclear Cells by Size Exclusion Liquid Chromatography Coupled to UV and ICP-MS Detection

Journal of Chromatographic Science. Oct, 2010  |  Pubmed ID: 20875230

An analytical methodology is presented in this work to determine metal-biomolecule complexes size distribution patterns of several elements, among different compounds present in human peripheral blood mononuclear cells (PBMC). A hyphenated technique based on size exclusion chromatography (SEC) coupled online to UV and inductively coupled plasma mass spectrometry (ICP-MS) detection is used. Two different SEC columns with separation ranges between 1,500-1,000,000 relative molecular mass (M(r)) (Nanofilm SEC-250) and 5,000 and 100,000 relative molecular mass (M(r)) (TSK-Gel G2000 SW) are used with 10 mmol/L tris-HCl at pH 7.3 as mobile phase. Retention behavior (retention time and peak-area ratios) remained unchanged for several successive separations. Metal-containing compounds are found to a wide range of M(r). Copper-zinc superoxide dismutase, copper and zinc metallothionein, and copper and zinc transferrin are identified in PBMC samples. A high M(r) (147,000) metal-binding protein containing copper and zinc and a high M(r) (107,000) manganese-binding protein were also found; however, these remained unknown.

Selenium or Selenium Plus Folic Acid Intake Improves the Detrimental Effects of Ethanol on Pups' Selenium Balance

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Dec, 2010  |  Pubmed ID: 20875836

The levels of folic acid and selenium, two nutrients with antioxidant properties, decrease in dams exposed to ethanol during gestation and lactation. This decrease affects their antioxidant balance, and consequently the health of their offspring. In this study we have proved that a supplemented diet with Se (0.5 ppm) or with Se (0.5 ppm) plus folic acid (8 ppm) to ethanol-exposed (20%v/v) dams prevents the ethanol-provoked effects in their offspring's Se deposits. Se levels in milk, serum, urine, faeces and several tissues were measured by graphite-furnace atomic absorption spectrometry. Results show that ethanol decreases Se deposits in pups' heart, liver, kidney and testes. However Se levels in pancreas and in serum were increased by ethanol; it also compromised the weight and the length of the offspring at the end of lactation. Our supplemented diets to ethanol dams increased all of these impaired levels, and restored Se pancreas concentration to a control status. However Se-only therapy mainly displaces Se to serum, kidney and spleen, and co-treatment with Se plus folic acid, mainly displaces Se to liver and brain. This data demonstrate that the qualitative and quantitative Se organ deposits depend on ethanol consumption, Se status, and the presence of other antioxidants.

Nature of Bonding in Complexes Containing "supershort" Metal-metal Bonds. Raman and Theoretical Study of M2(dmp)4 [M = Cr (natural Abundance Cr, 50Cr, and 54Cr) and Mo; Dmp = 2,6-dimethoxyphenyl]

Journal of the American Chemical Society. Feb, 2010  |  Pubmed ID: 20092271

We report an investigation of complexes of the type M(2)(dmp)(4) (M = Mo, Cr; dmp = 2,6-dimethoxyphenyl) using resonance Raman (RR) spectroscopy, Cr isotopic substitution, and density functional theory (DFT) calculations. Assignment of the Mo-Mo stretching vibration in the Mo(2) species is straightforward, as evidenced by a single resonance-enhanced band at 424 cm(-1), consistent with an essentially unmixed metal-metal stretch, and overtones of this vibration. On the other hand, the Cr(2) congener has no obvious metal-metal stretching mode near 650-700 cm(-1), where empirical predictions based on the Cr-Cr distance as well as DFT calculations suggest that this vibration should appear if unmixed. Instead, three bands are observed at 345, 363, and 387 cm(-1) that (a) have relative RR intensities that are sensitive to the Raman excitation frequency, (b) exhibit overtones and combinations in the RR spectra, and (c) shift in frequency upon isotopic substitution ((50)Cr and (54)Cr). DFT calculations are used to model the vibrational data for the Mo(2) and Cr(2) systems. Both the DFT results and empirical predictions are in good agreement with experimental observations in the Mo(2) complex, but both, while mutually consistent, differ radically from experiment in the Cr(2) complex. Our experimental and theoretical results, especially the Cr isotope shifts, clearly demonstrate that the potential energy of the Cr-Cr stretching coordinate is distributed among several normal modes having both Cr-Cr and Cr-ligand character. The general significance of these results in interpreting spectroscopic observations in terms of the nature of metal-metal multiple bonding is discussed.

Global Screening of Potential Candida Albicans Biofilm-related Transcription Factors Via Network Comparison

BMC Bioinformatics. 2010  |  Pubmed ID: 20102611

Candida albicans is a commonly encountered fungal pathogen in humans. The formation of biofilm is a major virulence factor in C. albicans pathogenesis and is related to antidrug resistance of this organism. Although many factors affecting biofilm have been analyzed, molecular mechanisms that regulate biofilm formation still await to be elucidated.

Capillary Supply to the Sinus Node in Subjects with Long-term Atrial Fibrillation

The Annals of Thoracic Surgery. Jan, 2010  |  Pubmed ID: 20103202

Atrial ischemia, and sinus node ischemia in particular, may be involved in the pathogenesis of atrial fibrillation. In this study we compared the sinus node blood capillary content in normal hearts in sinus rhythm and in pathologic hearts with chronic atrial fibrillation and we analyzed the ultrastructural features of such capillaries.

A Calixarene Dendron with Surface Congestion at the First Generation

Chemical Communications (Cambridge, England). Feb, 2010  |  Pubmed ID: 20126707

The X-ray structure of a dendrimeric receptor based on calixarenes showed a packed periphery in the first generation. The presence of urea groups as linkers between the calix[4]arene core and the calix[6]arene dendrons makes it a good model as an endo-receptor which is able to coordinate squarate dianions with a high association constant.

Multiscale AM-FM Methods for Diabetic Retinopathy Lesion Detection

IEEE Transactions on Medical Imaging. Feb, 2010  |  Pubmed ID: 20129850

In this paper, we propose the use of multiscale amplitude-modulation-frequency-modulation (AM-FM) methods for discriminating between normal and pathological retinal images. The method presented in this paper is tested using standard images from the early treatment diabetic retinopathy study. We use 120 regions of 40 x 40 pixels containing four types of lesions commonly associated with diabetic retinopathy (DR) and two types of normal retinal regions that were manually selected by a trained analyst. The region types included microaneurysms, exudates, neovascularization on the retina, hemorrhages, normal retinal background, and normal vessels patterns. The cumulative distribution functions of the instantaneous amplitude, the instantaneous frequency magnitude, and the relative instantaneous frequency angle from multiple scales are used as texture feature vectors. We use distance metrics between the extracted feature vectors to measure interstructure similarity. Our results demonstrate a statistical differentiation of normal retinal structures and pathological lesions based on AM-FM features. We further demonstrate our AM-FM methodology by applying it to classification of retinal images from the MESSIDOR database. Overall, the proposed methodology shows significant capability for use in automatic DR screening.

Large Changes in Electronic Structures of Ru2(6+) Species Caused by the Variations of the Bite Angle of Guanidinate Ligands: Tuning Magnetic Behavior

Inorganic Chemistry. Mar, 2010  |  Pubmed ID: 20151686

Syntheses and characterization of two Ru(2)(6+) paddlewheel compounds having very different magnetic behavior are reported. The compounds Ru(2)(tbn)(4)Cl(2), 1, and Ru(2)(tbo)(4)Cl(2), 2 (where tbn = the anion of 1,5,7-triazabicyclo[4.3.0]non-6-ene and tbo = the anion of 1,4,6-triazabicyclo[3.3.0]oct-4-ene), have four equatorial bicyclic guanidinate ligands and two chloride ions in axial positions. They show large disparity in Ru-Ru distances of about 0.11 A (2.389(3) and 2.499(3) A at 30 K for 1 and 2, respectively) that is attributed to the divergence in the bite angle of the ligand. Variable temperature structural data show no significant changes in the Ru-Ru distances between 30 and 213 K suggesting that the electronic structure remains unchanged in this temperature range for both compounds. Magnetic studies of 1 indicate there are two unpaired electrons at room temperature but the compound behaves as essentially diamagnetic at approximately 2 K. Compound 2 is non-magnetic across all temperatures in the range of 2 to 300 K. Density functional theory calculations suggest a pi(4)pi*(4)delta(2) electronic configuration for 2, while the magnetic behavior and structural data for 1 are consistent with a sigma(2)pi(4)delta(2)pi*(2) electronic configuration. This shows the importance of the ligand bite angle in determining the electronic configuration of the diruthenium unit and a way to tune magnetic behavior.

How "sweet" Complexity is and How "bitter" Variability Can Be; the New Aspect of Intensive Care Unit Hyperglycemia

Critical Care Medicine. Mar, 2010  |  Pubmed ID: 20168163

The Smallest Known Genomes of Multicellular and Toxic Cyanobacteria: Comparison, Minimal Gene Sets for Linked Traits and the Evolutionary Implications

PloS One. 2010  |  Pubmed ID: 20169071

Cyanobacterial morphology is diverse, ranging from unicellular spheres or rods to multicellular structures such as colonies and filaments. Multicellular species represent an evolutionary strategy to differentiate and compartmentalize certain metabolic functions for reproduction and nitrogen (N(2)) fixation into specialized cell types (e.g. akinetes, heterocysts and diazocytes). Only a few filamentous, differentiated cyanobacterial species, with genome sizes over 5 Mb, have been sequenced. We sequenced the genomes of two strains of closely related filamentous cyanobacterial species to yield further insights into the molecular basis of the traits of N(2) fixation, filament formation and cell differentiation. Cylindrospermopsis raciborskii CS-505 is a cylindrospermopsin-producing strain from Australia, whereas Raphidiopsis brookii D9 from Brazil synthesizes neurotoxins associated with paralytic shellfish poisoning (PSP). Despite their different morphology, toxin composition and disjunct geographical distribution, these strains form a monophyletic group. With genome sizes of approximately 3.9 (CS-505) and 3.2 (D9) Mb, these are the smallest genomes described for free-living filamentous cyanobacteria. We observed remarkable gene order conservation (synteny) between these genomes despite the difference in repetitive element content, which accounts for most of the genome size difference between them. We show here that the strains share a specific set of 2539 genes with >90% average nucleotide identity. The fact that the CS-505 and D9 genomes are small and streamlined compared to those of other filamentous cyanobacterial species and the lack of the ability for heterocyst formation in strain D9 allowed us to define a core set of genes responsible for each trait in filamentous species. We presume that in strain D9 the ability to form proper heterocysts was secondarily lost together with N(2) fixation capacity. Further comparisons to all available cyanobacterial genomes covering almost the entire evolutionary branch revealed a common minimal gene set for each of these cyanobacterial traits.

Actions of Vitamin D Are Mediated by the TLR4 Pathway in Inflammation-induced Colon Cancer

The Journal of Steroid Biochemistry and Molecular Biology. Jul, 2010  |  Pubmed ID: 20214986

Many chronic inflammatory diseases are associated with increased risk of developing cancer. In the colon, strong support for a link between chronic inflammation and cancer extends, in part, from population-based studies of persons with inflammatory bowel disease (IBD). Patients with IBD are at increased risk of developing colorectal cancer (CRC). The general consensus is that IBD results from the combined effects of genetics and environment factors known to affect the immune system. Vitamin D, an important regulator of the immune system, has been linked to IBD. Despite the strong potential reported for 1,25-dihydroxyvitamin D (1,25-OH)2D), its effects on calcium metabolism limits its application. Recently, less active vitamin D metabolites, cholecalciferol and 25-hydroxyvitamin D (25(OH)D), have gained considerable attention as promising agents against IBD-related colon cancer. Yet, their anti-proliferative properties and mechanism of action remain to be better defined. We present several signaling pathways commonly regulated by vitamin D compounds and highlight their regulation on TLR4. The efficacy of 25(OH)D and 1alpha-hydroxyviatmin D5 are evaluated using the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced IBD-related colon carcinogenesis model. In summary, vitamin D supplementation may provide a cost-effective approach to reduce IBD related colon cancer.

Cancer Chemoprevention by Natural Products: How Far Have We Come?

Pharmaceutical Research. Jun, 2010  |  Pubmed ID: 20238150

Since ancient times, natural products, herbs and spices have been used for preventing several diseases, including cancer. The term chemoprevention was coined in the late 1970s and referred to the prevention of cancer by selective use of phytochemicals or their analogs. The field utilizes experimental carcinogenesis models to examine the efficacy of chemopreventive agents in a stage-specific manner. The concept of using naturally derived chemicals as potential chemopreventive agents has advanced the field dramatically. Throughout the years, a vast number of chemopreventive agents present in natural products have been evaluated using various experimental models. A number of them have progressed to early clinical trials. More recently, the focus has been directed towards molecular targeting of chemopreventive agents to identify mechanism(s) of action of these newly discovered bioactive compounds. Moreover, it has been recognized that single agents may not always be sufficient to provide chemopreventive efficacy, and, therefore, the new concept of combination chemoprevention by multiple agents or by the consumption of "whole foods" has become an increasingly attractive area of study. Novel technologies, such as nanotechnology, along with a better understanding of cancer stem cells, are certain to continue the advancement of the field of cancer chemoprevention in years to come.

A New Role for the Virtual Crossmatch in Kidney Allograft Reuse

Transplantation. Mar, 2010  |  Pubmed ID: 20308864

Cervical Cancer Screening with Naked-eye Visual Inspection in Colombia

International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. Jun, 2010  |  Pubmed ID: 20347442

To assess the accuracy of visual inspection provided by nurses through combining acetic acid (VIA) and Lugol's iodine (VILI) in a low-resource region of Colombia.

Fate of a Pseudomonas Savastanoi Pv. Savastanoi Type III Secretion System Mutant in Olive Plants (Olea Europaea L.)

Applied and Environmental Microbiology. Jun, 2010  |  Pubmed ID: 20363790

Pseudomonas savastanoi pv. savastanoi strain NCPPB 3335 is a model bacterial pathogen for studying the molecular basis of disease production in woody hosts. We report the sequencing of the hrpS-to-hrpZ region of NCPPB 3335, which has allowed us to determine the phylogenetic position of this pathogen with respect to previously sequenced Pseudomonas syringae hrp clusters. In addition, we constructed a mutant of NCPPB 3335, termed T3, which carries a deletion from the 3' end of the hrpS gene to the 5' end of the hrpZ operon. Despite its inability to multiply in olive tissues and to induce tumor formation in woody olive plants, P. savastanoi pv. savastanoi T3 can induce knot formation on young micropropagated olive plants. However, the necrosis and formation of internal open cavities previously reported in knots induced by the wild-type strain were not observed in those induced by P. savastanoi pv. savastanoi T3. Tagging of P. savastanoi pv. savastanoi T3 with green fluorescent protein (GFP) allowed real-time monitoring of its behavior on olive plants. In olive plant tissues, the wild-type strain formed aggregates that colonized the intercellular spaces and internal cavities of the hypertrophic knots, while the mutant T3 strain showed a disorganized distribution within the parenchyma of the knot. Ultrastructural analysis of knot sections revealed the release of extensive outer membrane vesicles from the bacterial cell surface of the P. savastanoi pv. savastanoi T3 mutant, while the wild-type strain exhibited very few vesicles. This phenomenon has not been described before for any other bacterial phytopathogen during host infection.

X-ray Thomson Scattering in Warm Dense Matter at Low Frequencies

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Mar, 2010  |  Pubmed ID: 20365878

The low-frequency portion of the x-ray Thomson scattering spectrum is determined by electrons that follow the slow ion motion. This ion motion is characterized by the ion-ion dynamic structure factor, which contains a wealth of information about the ions, including structure and collective modes. The frequency-integrated (diffraction) contribution is considered first. An effective dressed-particle description of warm dense matter is derived from the quantum Ornstein-Zernike equations, and this is used to identify a Yukawa model for warm dense matter. The efficacy of this approach is validated by comparing a predicted structure with data from the extreme case of a liquid metal; good agreement is found. A Thomas-Fermi model is then introduced to allow the separation of bound and free states at finite temperatures, and issues with the definition of the ionization state in warm dense matter are discussed. For applications, analytic structure factors are given on either side of the Kirkwood line. Finally, several models are constructed for describing the slow dynamics of warm dense matter. Two classes of models are introduced that both satisfy the basic sum rules. One class of models is the "plasmon-pole"-like class, which yields the dispersion of ion-acoustic waves. Damping is then included via generalized hydrodynamics models that incorporate viscous contributions.

Annotation and Overview of the Pseudomonas Savastanoi Pv. Savastanoi NCPPB 3335 Draft Genome Reveals the Virulence Gene Complement of a Tumour-inducing Pathogen of Woody Hosts

Environmental Microbiology. Jun, 2010  |  Pubmed ID: 20370821

Pseudomonas savastanoi pv. savastanoi is a tumour-inducing pathogen of Olea europaea L. causing olive knot disease. Bioinformatic analysis of the draft genome sequence of strain NCPPB 3335, which encodes 5232 predicted coding genes on a total length of 5856 998 bp and a 57.12% G + C, revealed a large degree of conservation with Pseudomonas syringae pv. phaseolicola 1448A and P. syringae pv. tabaci 11528. However, NCPPB 3335 contains twelve variable genomic regions, which are absent in all previously sequenced P. syringae strains. Various features that could contribute to the ability of this strain to survive in a woody host were identified, including broad catabolic and transport capabilities for degrading plant-derived aromatic compounds, the duplication of sequences related to the biosynthesis of the phytohormone indoleacetic acid (iaaM, iaaH) and its amino acid conjugate indoleacetic acid-lysine (iaaL gene), and the repertoire of strain-specific putative type III secretion system effectors. Access to this seventh genome sequence belonging to the 'P. syringae complex' allowed us to identify 73 predicted coding genes that are NCPPB 3335-specific. Results shown here provide the basis for detailed functional analysis of a tumour-inducing pathogen of woody hosts and for the study of specific adaptations of a P. savastanoi pathovar.

CdnL, a Member of the Large CarD-like Family of Bacterial Proteins, is Vital for Myxococcus Xanthus and Differs Functionally from the Global Transcriptional Regulator CarD

Nucleic Acids Research. Aug, 2010  |  Pubmed ID: 20371514

CarD, a global transcriptional regulator in Myxococcus xanthus, interacts with CarG via CarDNter, its N-terminal domain, and with DNA via a eukaryotic HMGA-type C-terminal domain. Genomic analysis reveals a large number of standalone proteins resembling CarDNter. These constitute, together with the RNA polymerase (RNAP) interacting domain, RID, of transcription-repair coupling factors, the CarD_TRCF protein family. We show that one such CarDNter-like protein, M. xanthus CdnL, cannot functionally substitute CarDNter (or vice versa) nor interact with CarG. Unlike CarD, CdnL is vital for growth, and lethality due to its absence is not rescued by homologs from various other bacteria. In mycobacteria, with no endogenous DksA, the function of the CdnL homolog mirrors that of Escherichia coli DksA. Our finding that CdnL, like DksA, is indispensable in M. xanthus implies that they are not functionally redundant. Cells are normal on CdnL overexpression, but divide aberrantly on CdnL depletion. CdnL localizes to the nucleoid, suggesting piggyback recruitment by factors such as RNAP, which we show interacts with CdnL, CarDNter and RID. Our study highlights a complex network of interactions involving these factors and RNAP, and points to a vital role for M. xanthus CdnL in an essential DNA transaction that affects cell division.

Valorisation of Waste Tyre by Pyrolysis in a Moving Bed Reactor

Waste Management (New York, N.Y.). Jul, 2010  |  Pubmed ID: 19896820

The aim of this work is to assess the behaviour of a moving bed reactor, based on a screw transporter design, in waste tyre pyrolysis under several experimental conditions. Waste tyre represents a significant problem in developed countries and it is necessary to develop new technology that could easily process big amounts of this potentially raw material. In this work, the influence of the main pyrolysis process variables (temperature, solid residence time, mass flow rate and inert gas flow) has been studied by a thorough analysis of product yields and properties. It has been found that regardless the process operational parameters, a total waste tyre devolatilisation is achieved, producing a pyrolytic carbon black with a volatile matter content under 5 wt.%. In addition, it has been proven that, in the range studied, the most influencing process variables are temperature and solid mass flow rate, mainly because both variables modify the gas residence time inside the reactor. In addition, it has been found that the modification of these variables affects to the chemical properties of the products. This fact is mainly associated to the different cracking reaction of the primary pyrolysis products.

Proliferating NK Cells in Response to IL-15 Do Not Upregulate Surface B220 in Vivo

Gene Therapy. May, 2010  |  Pubmed ID: 19865177

[Brain Abscess Due to Listeria Monocytogenes in Adults: Six Cases and Review of the Literature]

Enfermedades Infecciosas Y Microbiología Clínica. Feb, 2010  |  Pubmed ID: 19800714

Listeria monocytogenes is a gram-positive bacillus, with special tropism for the central nervous system (CNS). Brain abscess caused by Listeria has not been extensively studied, although it accounts for 10% of CNS infections due to this microorganism.

Prevalence of Drug Resistance and Importance of Viral Load Measurements in Honduran HIV-infected Patients Failing Antiretroviral Treatment

HIV Medicine. Feb, 2010  |  Pubmed ID: 19686436

The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals.

[Medical Reflections on a Case of Pulmonary Thromboembolism in Pregnancy.]

Archivos De Cardiologia De Mexico. oct-dec, 2010  |  Pubmed ID: 21169090

Maternal mortality is still high in the world. Pulmonary thromboembolism as a cause of death is the second in developed countries. The frequency of reported events in Latin-American is 0.6%, which contrasts with that reported for developed countries (14.9%). This difference may be related to information bias. A review of the current information about this topic is presented, and we report a short case of a pregnant woman who presented pulmonary thromboembolism event at 30 weeks of pregnancy. Appropriate therapy allowed maternal and fetal survival.

Decrease of Spasticity with Muscle Vibration in Patients with Spinal Cord Injury

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Jun, 2011  |  Pubmed ID: 21172739

Spasticity is common after spinal cord injury (SCI). Exaggerated tendon jerks, clonus, and spasms are key features of spasticity that result from hyperexcitability of the stretch reflex circuit. Here we studied the effects of vibration on the rectus femoris muscle (RF) on clinical and electrophysiological measures of spasticity in the leg.

Neurosarcoidosis: Report of 30 Cases and a Literature Survey

European Journal of Internal Medicine. Dec, 2011  |  Pubmed ID: 22075297

Neurosarcoidosis accounts for approximately 5% of cases of sarcoidosis.

Fatty Infiltration Around the Cardiac Nodes

Revista Espanola De Cardiologia. Nov, 2011  |  Pubmed ID: 22116004

Physical Activity Patterns in Normal-weight Adolescents on Week-days and Week-ends

The Journal of Sports Medicine and Physical Fitness. Dec, 2011  |  Pubmed ID: 22212268

This study aimed to assess the day-to-day variability of children's physical activity by accelerometer on week-days and week-end days, and to determine the proportion of children that comply with the established physical activity (PA) guidelines.

[Nursing Registers on Sleep and Patient Perception in a Psychiatric Unit. A Comparative Study]

Anales Del Sistema Sanitario De Navarra. Sep-Dec, 2011  |  Pubmed ID: 22233841

Insomnia is a frequent problem in people who suffer from mental illnesses. The nursing staff control and register whether or not patients sleep. The aim of this article is to analyze the concordance between the perceptions of the patients of a psychiatric unit on the quality of sleep, and the notes in this respect contained in the nursing records.

Comprehensive Evaluation of Cervical Cancer Screening Programs: the Case of Colombia

Salud Pública De México. Nov-Dec, 2011  |  Pubmed ID: 22282139

To identify critical screening program factors for reducing cervical cancer mortality in Colombia.

Case Report of Electroconvulsive Therapy in a Patient with Parkinson Disease Concomitant with Deep Brain Stimulation

The Journal of ECT. Mar, 2011  |  Pubmed ID: 20386114

We report on a 56-year-old woman with Parkinson disease who had previously been implanted with bilateral deep brain stimulation (DBS). She was hospitalized after a 2-year course of severe depression with psychotic features and physical as well as mental decline. She underwent 2 rounds of successful electroconvulsive therapy (ECT), improving both her physical and mental health without any adverse effects to the patient or the DBS. This is a fourth reported case of ECT being successfully and safely administered in a patient implanted with DBS. This is the first case report of bitemporal ECT in a patient with bilateral DBS. It is also the first case report using the MECTA device and the first case report of a successful and safe second course of ECT after relapse of this patient's depression.

Incidence of Myelodysplastic Syndromes in Patients Receiving Concurrent Myelosuppressive Chemotherapy and Pegfilgrastim

Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners. Dec, 2011  |  Pubmed ID: 20876080

The World Health Organization classifies myelodysplastic syndromes (MDS) as a group of hematologic malignancies where at least one myeloid lineage contains ≥10% cells with myelodysplasia. Therapy-related MDS (t-MDS) may result from treatment with myelosuppressive chemotherapy and/or radiation. Myeloid growth factors, such as pegfilgrastim, have also been investigated as a possible risk factor for development of t-MDS. National guidelines and myeloid growth factor prescribing information recommend administering myeloid growth factors after a minimum of 24 h following myelosuppressive chemotherapy. Some evidence suggests that administering myeloid growth factors and myelosuppressive chemotherapy concurrently may increase the risk of developing t-MDS.

Analysis of the Presence of Cell Proliferation-related Molecules in the Tgf-β3 Null Mutant Mouse Palate Reveals Misexpression of EGF and Msx-1

Cells, Tissues, Organs. 2011  |  Pubmed ID: 20881363

The Tgf-β(3) null mutant mouse palate presents several cellular anomalies that lead to the appearance of cleft palate. One of them concerns the cell proliferation of both the palatal medial edge epithelium and mesenchyme. In this work, our aim was to determine whether there was any variation in the presence/distribution of several cell proliferation-related molecules that could be responsible for the cell proliferation defects observed in these palates. Our results showed no difference in the presence of EGF-R, PDGF-A, TGF-β(2), Bmp-2, and Bmp-4, and differences were minimal for FGF-10 and Shh. However, the expression of EGF and Msx-1 changed substantially. The shift of the EGF protein expression was the one that most correlated with that of cell proliferation. This molecule is regulated by TGF-β(3), and experiments blocking its activity in culture suggest that EGF misexpression in the Tgf-β(3) null mutant mouse palate plays a role in the cell proliferation defect observed.

An Uncommon Highly Oxidized Multiple Bonded Re2(8+) Species

Chemical Communications (Cambridge, England). Aug, 2011  |  Pubmed ID: 21738924

A long-sought metal-metal bonded species with an M(2)(8+) core has been structurally characterized. The diamagnetic compound {[Re(2)(hpp)(3)(OH)(O(3)SCF(3))](2)(μ-O)(2)}(O(3)SCF(3))(2), 2, has two σ(2)π(4) electron-poor triple-bonded Re(2)(8+) units embraced by three bicyclic guanidinate ligands (hpp) and axial OH and triflate groups; the two dimetal units are held together by bridging oxo-groups.

Efficacy of Tigecycline Alone and with Rifampin in Foreign-body Infection by Methicillin-resistant Staphylococcus Aureus

The Journal of Infection. Sep, 2011  |  Pubmed ID: 21763722

Tigecycline appears as an alternative therapy against methicillin-resistant Staphylococcus aureus (MRSA) with limited clinical experience. We evaluate the efficacy of tigecycline and its combination with rifampin in comparison to that for vancomycin in a rat model of foreign-body infection by MRSA.

Simon Bolivar's Remains Revisited: Getting out or Deeper into His Medical Labyrinth?

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Aug, 2011  |  Pubmed ID: 21765084

Mechanisms of Action of a Dual Cdc7/Cdk9 Kinase Inhibitor Against Quiescent and Proliferating CLL Cells

Molecular Cancer Therapeutics. Sep, 2011  |  Pubmed ID: 21768328

In chronic lymphocytic leukemia (CLL) the proliferation rate and resistance to drug-induced apoptosis are recognized as important factors in the outcome of treatment. In this study, we assess the activity and the mechanism of action of the prototype cell division cycle kinase 7 (Cdc7) inhibitor, PHA-767491, which inhibits the initiation of DNA replication but also has cyclin-dependent kinase 9 (Cdk9) inhibitory activity. We have studied the effects of this dual Cdc7/Cdk9 inhibitor in both quiescent CLL cells and CLL cells that have been induced to proliferate using a cellular coculture system that mimics the lymph node microenvironment. We find that this compound, originally developed as a DNA replication inhibitor, is particularly active in promoting mitochondrial dependent apoptosis in quiescent CLL cells purified from peripheral blood of patients regardless of recognized risk factors. In this setting, apoptosis is preceded by a decrease in the levels of Mcl-1 protein and transcript possibly due to inhibition of Cdk9. Following stimulation by CD154 and interleukin-4, CLL cells become highly chemoresistant, reenter into the cell cycle, reexpress Cdc7 kinase, a key molecular switch for the initiation of DNA replication, replicate their DNA, and undergo cell division. In this context, treatment with PHA-767491 abolished DNA synthesis by inhibiting Cdc7 but is less effective in triggering cell death, although Mcl-1 protein is no longer detectable. Thus, dual Cdc7/Cdk9 inhibition has the potential to target both the quiescent and actively proliferating CLL populations through two distinct mechanisms and may be a new therapeutic strategy in CLL.

Novel Segmentation Method for Abdominal Fat Quantification by MRI

Journal of Magnetic Resonance Imaging : JMRI. Oct, 2011  |  Pubmed ID: 21769972

To introduce and describe the feasibility of a novel method for abdominal fat segmentation on both water-saturated and non-water-saturated MR images with improved absolute fat tissue quantification.

In Vitro Cytotoxic Activity of Abietane Diterpenes from Peltodon Longipes As Well As Salvia Miltiorrhiza and Salvia Sahendica

Bioorganic & Medicinal Chemistry. Aug, 2011  |  Pubmed ID: 21775156

Phytochemical investigations of the n-hexane extract from the roots of Peltodon longipes (Lamiaceae) resulted in the isolation of 12 known abietane diterpenes (1-12). Structures were established on the basis of one and two dimensional nuclear magnetic resonance spectroscopic data ((1)H and (13)C, COSY, HSQC and HMBC), electron ionization mass spectrometric analysis (EIMS) as well as comparison with data from literature. These compounds, as well as eight known diterpenes (13-19) from Salvia miltiorrhiza, and two from Salvia sahendica (20 and 21) were evaluated for their cytotoxic effects in human pancreatic (MIAPaCa-2) and melanoma (MV-3) tumor cell lines using the MTT assay. Tanshinone IIa (13), 7α-acetoxyroyleanone (1), 1,2-dihydrotanshinone (16) and cryptotanshinone (14) had the highest cytotoxic effects in MIAPaCa-2, displaying IC(50) of 1.9, 4.7, 5.6, and 5.8 μM, respectively. Structure-activity relationships of abietane diterpenoid quinones are discussed.

[Medical Nutritional Therapy and Therapeutic Patient Education in Diabetes]

Revista De Enfermería (Barcelona, Spain). May, 2011  |  Pubmed ID: 21776930

This article includes an introduction to the current approach to dietary treatment of diabetes. Are provided the nutritional recommendations to primary secondary and tertiary prevention of diabetes, as recommended by the American Diabetes Association (ADA) adapted to different types of diabetes, treatments and special situations. Secondly, it introduces the concept of Therapeutic Education, especially education and nutritional diet for persons with diabetes and their families, the educational objectives in food according to type of diabetes type 1 or type 2 in different treatment modalities and educational strategies recommended by the Diabetes Education Study Group (wear) of the European Association for the Study of Diabetes (EASD) to facilitate better adherence to dietary treatment.

Beta-1 and Beta-2 Adrenergic Receptor Polymorphism and Association with Cardiovascular Response to Orthostatic Screening

Autonomic Neuroscience : Basic & Clinical. Oct, 2011  |  Pubmed ID: 21807569

Variation in the beta-1 and beta-2 adrenergic receptor genes (ADRB1 and ADRB2, respectively) may influence cardiovascular reactivity including orthostatic stress. We tested this hypothesis in a head-up tilt (HUT) screening protocol in healthy young adults without history of syncope. Following brachial arterial catheter insertion, 120 subjects (age 18-40, 72 females, Caucasian) underwent 5min 60° HUT. Polymorphisms tested were: Ser49/Gly and Arg389/Gly in ADRB1; and Arg16/Gly, Gln27/Glu, and Thr164/Ile in ADRB2. Three statistical models (recessive, dominant, additive) were evaluated using general linear models with analysis for each physiologic variable. A recessive model demonstrated a significant association between Arg16/Gly and: absolute supine and upright HR; HUT-induced change in cardiac index (CI), stroke index (SI) and systemic vascular resistance (SVR); and supine and upright norepinephrine values. Blood pressure was not influenced by genotype. Fewer associations were present for other polymorphisms: Ser49/Gly and the change in SI (dominant model), and Arg389/Gly and supine and HUT norepinephrine (additive model). We conclude that in this population, there is a robust association between Arg16/Gly and HUT responses, such that 2 copies of Arg16 increase supine and upright HR, and greater HUT-induced decreases in CI and SI, with greater increases in SVR and norepinephrine. ADRB1 gene variation appears to impact SI and plasma NE levels but not HR. Whether ADRB2 gene variation is ultimately disease-causing or disease-modifying, this study suggests an association between Arg16/Gly and postural hemodynamics, with sympathetic noradrenergic activity affected in a similar direction. This may have implications in the development of orthostatic disorders.

Experimental and Theoretical Evidence of Aromatic Behavior in Heterobenzene-like Molecules with Metal-metal Multiple Bonds

Chemistry (Weinheim an Der Bergstrasse, Germany). Sep, 2011  |  Pubmed ID: 21818792

Binding two quadruply bonded dimolybdenum units [Mo(2)(DAniF)(3)](+) (DAniF=N,N'-di-p-anisylformamidinate) with two chalcogen atoms generated two molecules with a central core composed of a cyclic six-membered [Mo(2)](2)(μ-EH)(2) species (E=S in 1 and O in 3, and [Mo(2)] is a quadruple-bonded [Mo(2)(formamidinate)(3)] unit). Aerobic oxidation of 1 and 3 followed by concomitant deprotonation gave rise to the corresponding [Mo(2)](2)(μ-E)(2) compounds 2 and 4. The latter show a striking coplanarity and near-bond equalization of the Mo/E cluster. The oxidized species 2 and 4 are diamagnetic in the measured temperature range of 5 to 300 K, which is somewhat unexpected for molecules that have dimetal units with a σ(2)π(4)δ(1) electronic configuration. This suggests there are strong interactions between the dimolybdenum units through the E atoms. The large electronic delocalization of the δ electrons over the entire Mo/E core is supported by the exceptionally large potential separation for the two successive one-electron reductions of the linked Mo(2)(5+) units from the oxidized species (ΔE(½)=1.7 V for the sulfur analogue). This large electronic delocalization has an important effect on the NMR spectroscopic signals for the two sets of methine (N-(CH)-N) protons from the DAniF ligands. Those essentially parallel to the core, H(∥), and those essentially perpendicular to the core, H(⊥), exhibit downfield and upfield chemical shifts, respectively, that are separated by δ=1.32 ppm. The structural, electronic, magnetic, and chemical behaviors for 2 and 4 are consistent with aromaticity, with the [Mo(2)E(2)Mo(2)] cores that resemble the prototypical benzene molecule. Theoretical studies, including DFT calculations, natural bond orbital (NBO) analyses, and gauge-independent atomic orbital (GIAO) NMR spectroscopic calculations, are also consistent with the aromaticity of the [Mo(2)](2)(μ-E)(2) units being promoted by d(δ)(Mo(2))-p(π)(E) π conjugation. The cyclic π conjugation of the central moiety in 2 and 4 involves a total of six electrons with 2e from δ(Mo(2)) and 4e from p(π)(E) orbitals, thereby conforming to Hückel's rule when electrons in the MOs with δ character are considered part of the delocalized system.

The Thyroid Hormone-inactivating Type III Deiodinase is Expressed in Mouse and Human Beta-cells and Its Targeted Inactivation Impairs Insulin Secretion

Endocrinology. Oct, 2011  |  Pubmed ID: 21828183

Deiodinases are selenoproteins that activate or inactivate thyroid hormone. During vertebrate development, these pathways control thyroid hormone action in a cell-specific fashion explaining how systemic thyroid hormone can affect local control of tissue embryogenesis. Here we investigated the role of the thyroid hormone-inactivating deiodinase (D3) in pancreatic islet function and glucose homeostasis. D3 expression was determined by real-time PCR, immunofluorescence, and enzyme activity. Embryonic and adult wild-type mice and Mice with targeted disruption of Dio3 gene (D3KO) as well as human fetal pancreas and adult islets were studied. Insulin secretion was evaluated in adult mouse isolated islets. We found Dio3 gene expression and protein highly expressed in embryonic and adult pancreatic islets, predominantly in β-cells in both humans and mice. However, mRNA levels were barely detectable for both the thyroid hormone-activating deiodinases types 1 and 2. D3KO animals were found to be glucose intolerant due to in vitro and in vivo impaired glucose-stimulated insulin secretion, without changes in peripheral sensitivity to insulin. D3KO neonatal (postnatal day 0) and adult pancreas exhibited reduced total islet area due to reduced β-cell mass, insulin content, and impaired expression of key β-cells genes. D3 expression in perinatal pancreatic β-cells prevents untimely exposure to thyroid hormone, the absence of which leads to impaired β-cell function and subsequently insulin secretion and glucose homeostasis. An analogous role is likely in humans, given the similar D3 expression pattern.

Modeling the Cellular Impact of Nanoshell-based Biosensors Using Mouse Alveolar Macrophage Cultures

Metallomics : Integrated Biometal Science. Nov, 2011  |  Pubmed ID: 21858295

In this study, the relative toxicity of native gold-silica nanoshells (NS) has been compared to nanoshells modified with poly(ethylene glycol)-thiol (PEG-SH) and a Raman-active PEG, p-mercaptoaniline-poly(ethylene glycol) (pMA-PEG), in mouse alveolar macrophage cell cultures (RAW 264.7). The results from toxicity profiling using an MTT assay demonstrate that cell viability post-particle exposure is a function of three factors: nanoshell concentration, surface functionalization, and incubation time. By minimizing particle concentrations and incubation times, cell cultures are able to recover within 24 h of nanoshell removal, indicative of nanoshells having more of a cytostatic versus cytotoxic effect on macrophage cells. The mechanism of the cytostatic effect has been investigated by imaging the presence of reactive oxygen species (ROS) using a fluorescence assay kit (Image-iT™ LIVE) after the introduction of NS to the cell cultures. Elevated ROS signals are seen in the cells containing higher concentration of NS, and indicate that the major reason of toxicity may due to the oxidative stress caused by excess NS particles. Raman imaging experiments with pMA-PEG coated nanoshells showed that cells exposed for even short exposure times (∼2 h) retained those particles up to 24 h after exposure, while migration experiments suggest that surviving cells retain their nanoshells and may reallocate them to progeny cells upon cell division.

Trolox Reduces the Effect of Ethanol on Acetylcholine-induced Contractions and Oxidative Stress in the Isolated Rabbit Duodenum

Revista Española De Enfermedades Digestivas : Organo Oficial De La Sociedad Española De Patología Digestiva. Aug, 2011  |  Pubmed ID: 21867348

Trolox is a hydrophilic analogue of vitamin E and a free radical scavenger. Ethanol diminishes the amplitude of spontaneous contractions and acetylcholine (ACh)-induced contractions in rabbit duodenum. The aim of this work was to study the effect of Trolox on the alterations induced by ethanol on contractility and lipid peroxidation in the duodenum. The duodenal contractility studies in vitro were carried out in an organ bath and the levels of malondialdehyde and 4-hydroxyalkenals (MDA+4-HAD) were measured by spectrophotometry. Trolox increased the reduction induced by ethanol on the amplitude of spontaneous contractions in longitudinal muscle but not in circular muscle. Trolox 4 mM decreased the effects of ethanol on ACh-induced contractions and on MDA+4-HDA concentrations. We conclude that Trolox might prevent oxidative stress induced by ethanol in the duodenum.

Sentinel Network for Monitoring in Vitro Susceptibility of Plasmodium Falciparum to Antimalarial Drugs in Colombia: a Proof of Concept

Memórias Do Instituto Oswaldo Cruz. Aug, 2011  |  Pubmed ID: 21881766

Drug resistance is one of the principal obstacles blocking worldwide malaria control. In Colombia, malaria remains a major public health concern and drug-resistant parasites have been reported. In vitro drug susceptibility assays are a useful tool for monitoring the emergence and spread of drug-resistant Plasmodium falciparum. The present study was conducted as a proof of concept for an antimalarial drug resistance surveillance network based on in vitro susceptibility testing in Colombia. Sentinel laboratories were set up in three malaria endemic areas. The enzyme linked immunosorbent assay-histidine rich protein 2 and schizont maturation methods were used to assess the susceptibility of fresh P. falciparum isolates to six antimalarial drugs. This study demonstrates that an antimalarial drug resistance surveillance network based on in vitro methods is feasible in the field with the participation of a research institute, local health institutions and universities. It could also serve as a model for a regional surveillance network. Preliminary susceptibility results showed widespread chloroquine resistance, which was consistent with previous reports for the Pacific region. However, high susceptibility to dihydroartemisinin and lumefantrine compounds, currently used for treatment in the country, was also reported. The implementation process identified critical points and opportunities for the improvement of network sustainability strategies.

Nuclear Factor κB is a Key Transcription Factor in the Duodenal Contractility Alterations Induced by Lipopolysaccharide

Experimental Physiology. Nov, 2011  |  Pubmed ID: 21890516

Alterations in intestinal motility are one of the features of sepsis induced by lipopolysaccharide (LPS). This study investigated the role of the nuclear transcription factor κB (NF-κB) in the LPS-induced duodenal contractility alterations, generation of reactive oxygen species (ROS) and production of cytokines in rabbit duodenum. Rabbits were treated with saline, LPS, sulfasalazine + LPS, pyrrolidinedithiocarbamate (PDTC) + LPS or RO 106-9920 + LPS. Contractility studies were performed in an organ bath. The formation of products of oxidative damage to proteins (carbonyls) and lipids (malondialdehyde and 4-hydroxyalkenals) was quantified in intestinal tissue and plasma. The protein expression of NF-κB was measured by Western blot. The DNA binding activity of NF-κB was evaluated by transcription factor activity assay. The expression of interleukin-1β, tumour necrosis factor α (TNF-α), interleukin-6, interleukin-10 and interleukin-8 mRNA was determined by RT-PCR. Sulfasalazine, PDTC and RO 106-9920 blocked the inhibitory effect of LPS on contractions induced by ACh in the longitudinal smooth muscle of rabbit duodenum. Sulfasalazine, PDTC and RO 106-9920 reduced the increased levels of malondialdehyde and 4-hydroxyalkenals and the carbonyls induced by LPS in plasma. Lipopolysaccharide induced the activation, translocation to the nucleus and DNA binding of NF-κB. Lipopolysaccharide increased the mRNA expression of interleukin-6 and TNF-α in duodenal tissue, and this effect was partly reversed by PDTC, sulfasalazine and RO 106-9920. In conclusion, NF-κB mediates duodenal contractility disturbances, the generation of ROS and the increase in the expression of interleukin-6 and TNF-α induced by LPS. Sulfasalazine, PDTC and RO 106-9920 may be therapeutic drugs to reduce these effects.

Effects of Antioxidant Supplementation on Duodenal Se-Met Absorption in Ethanol-exposed Rat Offspring in Vivo

The Journal of Reproduction and Development. Dec, 2011  |  Pubmed ID: 21921432

The nutritional deficiencies provoked by ethanol consumption, during gestation or lactation, can contribute to multiple birth defects in offspring. In order to improve our knowledge about selenium (Se) distribution in pups exposed to ethanol, the present study evaluated the effect of this drug on intestinal development and determined its action on duodenal absorption of selenomethionine (Se-Met). To determinate if supplementation could improve Se absorption and its serum values, we used two antioxidant supplemented regimens on dams, with selenium alone or selenium plus folic acid, and obtained six groups of pups: C (control), A (alcohol), CS (control + Se), AS (alcohol + Se), CFS (control + Se + folic acid) and AFS (alcohol + Se + folic acid). Duodenal Se-Met transport was performed using an in vivo perfusion method. Se levels were measured by graphite furnace atomic absorption spectrometry. The supplemented diets utilized had a positive influence on body growth, duodenal perimeter and Se content in ethanol-exposed pups. Ethanol exposure increased Se-Met duodenal absorption in all pups, supplemented or not, presenting the highest values of maximal velocity (V(max)) compared with their control counterparts. The affinity constant (K(m)) increased according to rank: A>AS>AFS groups. These results suggest that although antioxidant supplementation does not restore Se-Met absorption to normal values, it enhances the affinity of the transporters for the substrate and improves the damage caused by ethanol in the duodenal mucosa.

Reducing Contamination of Peripheral Blood Cultures in a Pediatric Emergency Department

Pediatric Emergency Care. Oct, 2011  |  Pubmed ID: 21960090

Blood culture contamination rates (CRs) in emergency departments (EDs) vary from 1% to 9% in previous studies. High CRs cause unnecessary admissions, antibiotics, and costs. Different measures have been tried to improve CR. This study sought to determine the ED CR at Arkansas Children's Hospital (ACH) and evaluate an educational intervention.

Impact of Partial Volume Effects on Visceral Adipose Tissue Quantification Using MRI

Journal of Magnetic Resonance Imaging : JMRI. Dec, 2011  |  Pubmed ID: 21964770

To quantitatively estimate the impact of partial volume effects on visceral adipose tissue (VAT) quantification using typical resolution magnetic resonance imaging (MRI).

Long-term Risk of Recurrent Stroke in Young Cryptogenic Stroke Patients with and Without Patent Foramen Ovale

International Journal of Stroke : Official Journal of the International Stroke Society. Oct, 2011  |  Pubmed ID: 21978242

Background Among patients with a patent foramen ovale and cryptogenic ischemic stroke, the long-term prognosis is unclear. Aims This study aims to estimate the recurrence rate in young cryptogenic stroke patients with and without patent foramen ovale. Patients and methods One hundred eighty-six cryptogenic stroke patients (aged 18-45 years) were prospectively followed for up to five-years. They were divided into two groups according to the echocardiographic presence of patent foramen ovale. All patients received aspirin (100 mg/day) for secondary prevention. Results Mean age was 32·3 (standard deviation 7·9) years. During the mean follow-up of 66 months five patients with patent foramen ovale had recurrent strokes compared with 11 patients without patent foramen ovale. The average annual rate of recurrent cerebral ischemia was 1·1% and 1·6% for patients with and without patent foramen ovale, respectively. The recurrence rate did not increase with the presence of patent foramen ovale, atrial septal aneurysm or other variables. More than 60% of the reported cases achieved a good functional outcome. Conclusions Young patients with cryptogenic ischemic stroke with and without patent foramen ovale have a low recurrence rate in a long-term follow-up and most present a favorable outcome. Patent foramen ovale with or without atrial septal aneurysm did not increase the risk of recurrence.

Use of Dolls As a Therapeutic Intervention: Relationship to Previous Negative Behaviors and Pro Re Nata (prn) Haldol Use Among Geropsychiatric Inpatients

Archives of Psychiatric Nursing. Oct, 2011  |  Pubmed ID: 21978807

This exploratory study was conducted to determine the effects of use of dolls as a therapeutic intervention with geriatric inpatients. The sample included 115 patients, 29 of whom had an order for prn Haldol. Among patients who had previous negative behaviors, there was a lower average number of prn Haldol doses with those who had dolls. Recommendations for practice and future research are included.

Involvement of Neuronal Nitric Oxide Synthase (nNOS) in the Regulation of Migrating Motor Complex (MMC) in Sheep

Veterinary Journal (London, England : 1997). Oct, 2011  |  Pubmed ID: 21995890

The objectives of this study were to evaluate the role of nitric oxide (NO) synthase isoforms (nNOS, eNOS, and iNOS) in the regulation of the migrating motor complex (MMC) in sheep using electromyography and their expression in the gastrointestinal (GI) tract by Western blot (WB) and immunohistochemistry. Intravenous administration of L-NAME or the nNOS inhibitor 7-nitroindazole (7-NI) decreased the MMC interval. Myoelectric activity of intestinal phase II was increased, whereas antral activity was reduced. These effects were blocked by L-arginine. Inhibitors of either iNOS (aminoguanidine and S-methylisothiourea) or eNOS (L-NIO) were ineffective. The NO donor sodium nitroprusside decreased GI myoelectric activity, inhibited the MMC pattern, and prevented the effects induced by L-NAME and 7-NI in the intestine. Intracerebroventricular administration of these agents did not modify GI motility. In the rumen, abomasal antrum, duodenum, and jejunum, WB showed three bands at about 155, 145, and 135kDa corresponding to nNOS, and a 140-kDa band (eNOS); however iNOS was not detected. Positive nNOS immunostaining was observed in neurons of the myenteric and submucous plexus of all GI tissues, while eNOS was found in the endothelial cells, ruminal and intestinal epithelium, as well as in some enteric neurons and in endocrine-like cells of the duodenal Brunner's glands. In contrast, only weak iNOS immunoreactivity was found in ruminal epithelium. Taken together, our results suggest that NO, synthesized at a peripheral level by nNOS, is tonically inhibiting the MMC pattern and intestinal motility in sheep.

Synthesis and Biological Activity of New Bispyridinium Salts of 4,4'-bispyridyl-5,5'-perfluoroalkyl-2,2'-bisoxazoles

European Journal of Medicinal Chemistry. Nov, 2011  |  Pubmed ID: 21996467

A series of bispyridinium compounds were synthesized by a short sequence of reactions from symmetric diamides. All compounds were tested for their antiproliferative activity against HT-29, a cell line derived from a human colon adenocarcinoma, and their inhibitory activity against choline kinase (ChoK), a novel anticancer molecular target already in clinical trials. Most of the compounds analyzed showed good antiproliferative activities, in the micromolar range, with the identification of promising lead molecules as a new family of potential inhibitors of ChoK.

Impact of Digital Mammography in the Detection and Management of Microcalcifications

Radiologia. Oct, 2011  |  Pubmed ID: 22015223

OBJECTIVE: To determine whether the introduction of digital mammography in breast cancer screening has resulted in changes in the detection and management of microcalcifications. MATERIAL AND METHODS: We retrospectively studied the performance indicators of our breast cancer screening program that are related to the diagnosis of microcalcifications (rates of recall and recommendation of intermediate follow-up after screening, rate of indication of invasive procedures for microcalcifications and their positive predictive value, detection rate for microcalcifications, and number of ductal carcinomas in situ (DCIS) diagnosed). We compared the results obtained using direct digital mammography (september 2008-august 2009) with those obtained using analog mammography (september 2006-august 2007). STATISTICAL ANALYSIS: Chi-square test and measures of association. RESULTS: We found that using digital mammography led to significant increases in the recall rate (from 50.8 to 64‰), in the rate of intermediate follow-up after screening (from 9.41 to 18.7‰), in the rate of indication for invasive procedures (from 1.88 to 3.01‰), in the cancers detected through microcalcifications (from 0.86 to 1.36‰), and in the number of DCIS diagnosed. CONCLUSION: Direct digital mammography has improved the detection of microcalcifications, increasing the number of DCIS diagnosed without decreasing the positive predictive value of the invasive procedures indicated for microcalcifications. However, direct digital mammography has had a negative effect by increasing the recall rate and indication for short-term follow-up, possibly due to the difficulty of comparing the findings with those of earlier analog mammograms.

Preparation and Scintillating Properties of Sol-gel Eu, Tb Co-doped Lu(2)o(3) Nanopowders

International Journal of Molecular Sciences. 2011  |  Pubmed ID: 22016655

Nanocrystalline Eu(3+), Tb(3+) co-doped Lu(2)O(3) powders with a maximum size of 25.5 nm were prepared by the sol-gel process, using lutetium, europium and terbium nitrates as precursors, and ethanol as a solvent. Differential thermal analysis (DTA) and infrared spectroscopy (IR) were used to study the chemical changes during the xerogel annealing. After the sol evaporation at 100 °C, the formed gel was annealed from 300 to 900 °C for 30 min under a rich O(2) atmosphere, and the yielded product was analyzed by X-ray diffraction (XRD) to characterize the microstructural behavior and confirm the crystalline structure. The results showed that Lu(2)O(3) nanopowders start to crystallize at 400 °C and that the crystallite size increases along with the annealing temperature. A transmission electron microscopy (TEM) study of samples annealed at 700 and 900 °C was carried out in order to analyze the microstructure, as well as the size, of crystallites. Finally, in regard to scintillating properties, Eu(3+) dopant (5 mol%), Tb(3+) codoped Lu(2)O(3) exhibited a typical red emission at 611 nm (D(°)→(7)F(2)), furthermore, the effect of Tb(3+) molar content (0.01, 0.015 and 0.02% mol) on the Eu(3+) radioluminiscence was analyzed and it was found that the higher emission intensity corresponds to the lower Tb(3+) content.

Miniature Transposable Sequences Are Frequently Mobilized in the Bacterial Plant Pathogen Pseudomonas Syringae Pv. Phaseolicola

PloS One. 2011  |  Pubmed ID: 22016774

Mobile genetic elements are widespread in Pseudomonas syringae, and often associate with virulence genes. Genome reannotation of the model bean pathogen P. syringae pv. phaseolicola 1448A identified seventeen types of insertion sequences and two miniature inverted-repeat transposable elements (MITEs) with a biased distribution, representing 2.8% of the chromosome, 25.8% of the 132-kb virulence plasmid and 2.7% of the 52-kb plasmid. Employing an entrapment vector containing sacB, we estimated that transposition frequency oscillated between 2.6×10(-5) and 1.1×10(-6), depending on the clone, although it was stable for each clone after consecutive transfers in culture media. Transposition frequency was similar for bacteria grown in rich or minimal media, and from cells recovered from compatible and incompatible plant hosts, indicating that growth conditions do not influence transposition in strain 1448A. Most of the entrapped insertions contained a full-length IS801 element, with the remaining insertions corresponding to sequences smaller than any transposable element identified in strain 1448A, and collectively identified as miniature sequences. From these, fragments of 229, 360 and 679-nt of the right end of IS801 ended in a consensus tetranucleotide and likely resulted from one-ended transposition of IS801. An average 0.7% of the insertions analyzed consisted of IS801 carrying a fragment of variable size from gene PSPPH_0008/PSPPH_0017, showing that IS801 can mobilize DNA in vivo. Retrospective analysis of complete plasmids and genomes of P. syringae suggests, however, that most fragments of IS801 are likely the result of reorganizations rather than one-ended transpositions, and that this element might preferentially contribute to genome flexibility by generating homologous regions of recombination. A further miniature sequence previously found to affect host range specificity and virulence, designated MITEPsy1 (100-nt), represented an average 2.4% of the total number of insertions entrapped in sacB, demonstrating for the first time the mobilization of a MITE in bacteria.

The Influence of the Accessory Genome on Bacterial Pathogen Evolution

Mobile Genetic Elements. 5, 2011  |  Pubmed ID: 22016845

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens' frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorize the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution.

Sequence and Role in Virulence of the Three Plasmid Complement of the Model Tumor-inducing Bacterium Pseudomonas Savastanoi Pv. Savastanoi NCPPB 3335

PloS One. 2011  |  Pubmed ID: 22022435

Pseudomonas savastanoi pv. savastanoi NCPPB 3335 is a model for the study of the molecular basis of disease production and tumor formation in woody hosts, and its draft genome sequence has been recently obtained. Here we closed the sequence of the plasmid complement of this strain, composed of three circular molecules of 78,357 nt (pPsv48A), 45,220 nt (pPsv48B), and 42,103 nt (pPsv48C), all belonging to the pPT23A-like family of plasmids widely distributed in the P. syringae complex. A total of 152 coding sequences were predicted in the plasmid complement, of which 38 are hypothetical proteins and seven correspond to putative virulence genes. Plasmid pPsv48A contains an incomplete Type IVB secretion system, the type III secretion system (T3SS) effector gene hopAF1, gene ptz, involved in cytokinin biosynthesis, and three copies of a gene highly conserved in plant-associated proteobacteria, which is preceded by a hrp box motif. A complete Type IVA secretion system, a well conserved origin of transfer (oriT), and a homolog of the T3SS effector gene hopAO1 are present in pPsv48B, while pPsv48C contains a gene with significant homology to isopentenyl-diphosphate delta-isomerase, type 1. Several potential mobile elements were found on the three plasmids, including three types of MITE, a derivative of IS801, and a new transposon effector, ISPsy30. Although the replication regions of these three plasmids are phylogenetically closely related, their structure is diverse, suggesting that the plasmid architecture results from an active exchange of sequences. Artificial inoculations of olive plants with mutants cured of plasmids pPsv48A and pPsv48B showed that pPsv48A is necessary for full virulence and for the development of mature xylem vessels within the knots; we were unable to obtain mutants cured of pPsv48C, which contains five putative toxin-antitoxin genes.

Reconnaissance of Selected PPCP Compounds in Costa Rican Surface Waters

Water Research. Dec, 2011  |  Pubmed ID: 22048020

Eighty-six water samples were collected in early 2009 from Costa Rican surface water and coastal locations for the analysis of 34 pharmaceutical and personal care product compounds (PPCPs). Sampling sites included areas receiving treated and untreated wastewaters, and urban and rural runoff. PPCPs were analyzed using a combination of solid phase extraction and liquid chromatography tandem mass spectrometry. The five most frequently detected compounds were doxycycline (77%), sulfadimethoxine (43%), salicylic acid (41%), triclosan (34%) and caffeine (29%). Caffeine had the maximum concentration of 1.1 mg L(-1), possibly due to coffee bean production facilities upstream. Other compounds found in high concentrations include: doxycycline (74 μg L(-1)), ibuprofen (37 μg L(-1)), gemfibrozil (17 μg L(-1)), acetominophen (13 μg L(-1)) and ketoprofen (10 μg L(-1)). The wastewater effluent collected from an oxidation pond had similar detection and concentrations of compounds compared to other studies reported in the literature. Waters receiving runoff from a nearby hospital showed higher concentrations than other areas for many PPCPs. Both caffeine and carbamazepine were found in low frequency compared to other studies, likely due to enhanced degradation and low usage, respectively. Overall concentrations of PPCPs in surface waters of Costa Rica are inline with currently reported occurrence data from around the world, with the exception of doxycycline.

Diversity-oriented Synthesis of Macrocyclic Peptidomimetics

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2011  |  Pubmed ID: 21383137

Structurally diverse libraries of novel small molecules represent important sources of biologically active agents. In this paper we report the development of a diversity-oriented synthesis strategy for the generation of diverse small molecules based around a common macrocyclic peptidomimetic framework, containing structural motifs present in many naturally occurring bioactive compounds. Macrocyclic peptidomimetics are largely underrepresented in current small-molecule screening collections owing primarily to synthetic intractability; thus novel molecules based around these structures represent targets of significant interest, both from a biological and a synthetic perspective. In a proof-of-concept study, the synthesis of a library of 14 such compounds was achieved. Analysis of chemical space coverage confirmed that the compound structures indeed occupy underrepresented areas of chemistry in screening collections. Crucial to the success of this approach was the development of novel methodologies for the macrocyclic ring closure of chiral α-azido acids and for the synthesis of diketopiperazines using solid-supported N methylmorpholine. Owing to their robust and flexible natures, it is envisaged that both new methodologies will prove to be valuable in a wider synthetic context.

Breast Cancer Management in Middle-resource Countries (MRCs): Consensus Statement from the Breast Health Global Initiative

Breast (Edinburgh, Scotland). Apr, 2011  |  Pubmed ID: 21388811

In middle resource countries (MRCs), cancer control programs are becoming a priority as the pattern of disease shifts from infectious diseases to non-communicable diseases such as breast cancer, the most common cancer among women in MRCs. The Middle Resource Scenarios Working Group of the BHGI 2010 Global Summit met to identify common issues and obstacles to breast cancer detection, diagnosis and treatment in MRCs. They concluded that breast cancer early detection programs continue to be important, should include clinical breast examination (CBE) with or without mammography, and should be coupled with active awareness programs. Mammographic screening is usually opportunistic and early detection programs are often hampered by logistical and financial problems, as well as socio-cultural barriers, despite improved public educational efforts. Although multidisciplinary services for treatment are available, geographical and economic limitations to these services can lead to an inequity in health care access. Without adequate health insurance coverage, limited personal finances can be a significant barrier to care for many patients. Despite the improved availability of services (surgery, pathology, radiology and radiotherapy), quality assurance programs remain a challenge. Better access to anticancer drugs is needed to improve outcomes, as are rehabilitation programs for survivors. Focused and sustained government health care financing in MRCs is needed to improve early detection and treatment of breast cancer.

Intra- and Intergenerational Persistence of an Insect Nucleopolyhedrovirus: Adverse Effects of Sublethal Disease on Host Development, Reproduction, and Susceptibility to Superinfection

Applied and Environmental Microbiology. May, 2011  |  Pubmed ID: 21398487

Sublethal infections by Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) are common in field populations of the beet armyworm (S. exigua, Hübner) in the Almerian horticultural region of Spain. Inoculation of second, third, and fourth instars with occlusion bodies (OBs) of an isolate (VT-SeAl1) associated with vertically transmitted infections resulted in 15 to 100% of sublethal infection in adult survivors, as determined by reverse transcription-PCR (RT-PCR) detection of viral DNA polymerase transcripts, and quantitative PCR (qPCR) targeted at the DNA polymerase gene. The prevalence of adult sublethal infection was positively related to the inoculum OB concentration consumed during the larval stage. Sublethal infections persisted in OB-treated insects for at least five generations. Viral transcripts were more frequently detected in adult insects than in third instars. qPCR analysis indicated a consistently higher prevalence of sublethal infection than RT-PCR. Sublethal infection was associated with significant reductions in pupal weight, adult emergence, fecundity, and fertility (egg hatch) and significant increases in larval development time and duration of the preoviposition period. Insects taken from a persistently infected experimental population were significantly more susceptible to the OB inoculum than control insects that originated from the same virus-free colony as the persistently infected insects. We conclude that OB treatment results in rapid establishment of sublethal infections that persist between generations and which incur costs in the development and reproductive capacity of the host insect.

Short Communication: High Prevalence of Drug Resistance in HIV Type 1-infected Children Born in Honduras and Belize 2001 to 2004

AIDS Research and Human Retroviruses. Oct, 2011  |  Pubmed ID: 21417948

Antiretroviral therapy has had a great impact on the prevention of mother-to-child transmission (MTCT) of HIV-1. However, development of drug resistance, which could be subsequently transmitted to the child, is a major concern. In Honduras and Belize the prevalence of drug resistance among HIV-1-infected children remains unknown. A total of 95 dried blood spot samples was obtained from HIV-1-infected, untreated children in Honduras and Belize born during 2001 to 2004, when preventive antiretroviral therapy was often suboptimal and consisted of monotherapy with nevirapine or zidovudine. Partial HIV-1 pol gene sequences were successfully obtained from 66 children (Honduras n=55; Belize n=11). Mutations associated with drug resistance were detected in 13% of the Honduran and 27% of the Belizean children. Most of the mutations detected in Honduras (43%) and all mutations detected in Belize were associated with resistance to nonnucleoside reverse transcriptase inhibitors, which was expected from the wide use of nevirapine to prevent MTCT during the study period. In addition, although several mothers reported that they had not received antiretroviral therapy, mutations associated with resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors were found in Honduras. This suggests prior and unreported use of these drugs, or that these women had been infected with resistant virus. The present study demonstrates, for the first time, the presence of drug resistance-associated mutations in HIV-1-infected Honduran and Belizean children.

Contractile Effect of Tachykinins on Rabbit Small Intestine

Acta Pharmacologica Sinica. Apr, 2011  |  Pubmed ID: 21441943

To study the role of the tachykinin receptors in spontaneous contractions of longitudinal and circular smooth muscle from rabbit small intestine and to determine the mechanism of action of Substance P (SP).

Transcription Factor Foxd1 is Required for the Specification of the Temporal Retina in Mammals

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Apr, 2011  |  Pubmed ID: 21490208

The organization of the visual system is different in birds and mammals. In both, retinal axons project topographically to the visual targets in the brain; but whereas in birds visual fibers from the entire retina decussate at the optic chiasm, in mammals, a number of axons from the temporal retina diverge at the midline to project ipsilaterally. Gain-of-function experiments in chick raised the hypothesis that the transcription factor Foxd1 specifies retinal temporal identity. However, it remains unknown whether Foxd1 is necessary for this function. In mammals, the crucial role of Foxd1 in the patterning of the optic chiasm region has complicated the interpretation of its cell-autonomous function in the retina. Furthermore, target molecules identified for Foxd1 are different in chicks and mice, leading to question the function of Foxd1 in mammals. Here we show that in the mouse, Foxd1 imprints temporal features in the retina such as axonal ipsilaterality and rostral targeting in collicular areas and that EphA6 is a Foxd1 downstream effector that sends temporal axons to the rostral colliculus. In addition, our data support a model in which the desensitization of EphA6 by ephrinA5 in cis is not necessary for the proper functioning of EphA6. Overall, these results indicate that Foxd1 functions as a conserved determinant of temporal identity but reveal that the downstream effectors, and likely their mechanisms of action, are different in mammals and birds.

Role of TLR4 and MAPK in the Local Effect of LPS on Intestinal Contractility

The Journal of Pharmacy and Pharmacology. May, 2011  |  Pubmed ID: 21492167

Lipopolysaccharide (LPS) has been shown to alter intestinal contractility. Toll-like receptor 4 (TLR4), K(+) channels and mitogen-activated protein kinases (MAPKs) have been proposed to be involved in the mechanism of action of LPS. The aim of this study was to determine the role of TLR4, K(+) channels and MAPKs (p38, JNK and MEK1/2) in the local effect of LPS on the acetylcholine (ACh)-induced contractions in rabbit small intestine in vitro.

Light-dependent Gene Regulation by a Coenzyme B12-based Photoreceptor

Proceedings of the National Academy of Sciences of the United States of America. May, 2011  |  Pubmed ID: 21502508

Cobalamin (B(12)) typically functions as an enzyme cofactor but can also regulate gene expression via RNA-based riboswitches. B(12)-directed gene regulatory mechanisms via protein factors have, however, remained elusive. Recently, we reported down-regulation of a light-inducible promoter in the bacterium Myxococcus xanthus by two paralogous transcriptional repressors, of which one, CarH, but not the other, CarA, absolutely requires B(12) for activity even though both have a canonical B(12)-binding motif. Unanswered were what underlies this striking difference, what is the specific cobalamin used, and how it acts. Here, we show that coenzyme B(12) (5'-deoxyadenosylcobalamin, AdoB(12)), specifically dictates CarH function in the dark and on exposure to light. In the dark, AdoB(12)-binding to the autonomous domain containing the B(12)-binding motif foments repressor oligomerization, enhances operator binding, and blocks transcription. Light, at various wavelengths at which AdoB(12) absorbs, dismantles active repressor oligomers by photolysing the bound AdoB(12) and weakens repressor-operator binding to allow transcription. By contrast, AdoB(12) alters neither CarA oligomerization nor operator binding, thus accounting for its B(12)-independent activity. Our findings unveil a functional facet of AdoB(12) whereby it serves as the chromophore of a unique photoreceptor protein class acting in light-dependent gene regulation. The prevalence of similar proteins of unknown function in microbial genomes suggests that this distinct B(12)-based molecular mechanism for photoregulation may be widespread in bacteria.

Synthesis of a Stereochemically Diverse Library of Medium-sized Lactams and Sultams Via S(N)Ar Cycloetherification

ACS Combinatorial Science. Jul, 2011  |  Pubmed ID: 21526820

We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the synthesis of stereochemically diverse 8-membered lactam and sultam scaffolds via S(N)Ar cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd-mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The production of two 8000-membered libraries is discussed including a full analysis of library purity and property distribution. Library diversity was evaluated in comparison to the Molecular Library Small Molecule Repository (MLSMR) through the use of a multifusion similarity (MFS) map and principal component analysis (PCA).

Gene Expression of Pht Cluster Genes and a Putative Non-ribosomal Peptide Synthetase Required for Phaseolotoxin Production is Regulated by GacS/GacA in Pseudomonas Syringae Pv. Phaseolicola

Research in Microbiology. Jun, 2011  |  Pubmed ID: 21527339

Pseudomonas syringae pv. phaseolicola is the causal agent of halo blight disease of beans (Phaseolus vulgaris L.), which is characterized by watersoaked lesions surrounded by a chlorotic halo resulting from the action of a non-host specific toxin known as phaseolotoxin. This toxin inhibits the enzyme ornithine carbamoyltransferase involved in the arginine biosynthesis pathway. It was previously reported that genes within the Pht cluster were involved in the regulation and synthesis of phaseolotoxin. The GacS/GacA two-component signal transduction system controls important pathogenicity and virulence mechanisms in several Gram-negative bacteria. Tox(-) phenotype gacA(-) and gacS(-) mutants were obtained and gacA(-) transcriptome analysis revealed that this response activator controls expression of genes within the Pht cluster as well as another gene located in a different region in the bacterial chromosome and that has been unambiguously shown to be directly involved in phaseolotoxin biosynthesis. Results presented in this work suggest that phaseolotoxin biosynthesis involve elements within and outside the Pht Cluster, and that the GacS/GacA two-component system exerts control over them.

[Congenital Tracheal Bronchus]

Revista Española De Anestesiología Y Reanimación. Mar, 2011  |  Pubmed ID: 21534304

Structural and Conformational Analysis of Proanthocyanidins from Parapiptadenia Rigida and Their Wound-healing Properties

Journal of Natural Products. Jun, 2011  |  Pubmed ID: 21553897

Structure elucidation and conformation analysis of four proanthocyanidins isolated from the bark of Parapiptadenia rigida were performed by two-dimensional NMR spectroscopy, HRESIMS, CD, and molecular mechanics (MM+) force field calculations. The known prodelphinidin, epigallocatechin-(4β→8)-epigallocatechin-3-O-gallate (1) was accompanied by the new epigallocatechin-(4β→8)-4'-O-methylgallocatechin (2), epicatechin-(4β→8)-4'-O-methylgallocatechin (3), and (4α→8)-bis-4'-O-methylgallocatechin (4). Compound 4 was previously published but the earlier structure must presumably be revised to 4'-O-methylgallocatechin-(4α→8)-4'-O-methylepigallocatechin. Conformational studies showed the compact rotamer with B and E rings in quasi-equatorial orientations as the preferred conformation for compounds 1-3, whereas 4 consists of two stable rotamers, each with a quasi-equatorial orientation of ring B and E, respectively. The isolated compounds were studied for their wound-healing effects in a scratch assay and showed promising results.

Clinical Outcome and Microbiological Findings Using Antibiotic-loaded Spacers in Two-stage Revision of Prosthetic Joint Infections

The Journal of Infection. Jul, 2011  |  Pubmed ID: 21596440

Antibiotic-loaded spacers may improve antimicrobial efficacy in two-stage revision of prosthetic joint infections, but they may also interfere in the course of infection. This prospective study of prosthetic joint infections managed with two-stage revision and antibiotic-loaded spacers (2004-09) analyzes case outcomes and proposes a second-stage culture interpretation scheme.

Insulin Resistance and Hypertension in Patients with Type 1 Diabetes

Journal of Diabetes and Its Complications. Jul-Aug, 2011  |  Pubmed ID: 21601483

The aims of this study were to determine the prevalence of hypertension in type 1 diabetes patients and to analyze its relationship with insulin resistance and other associated factors.

Expanding the Clinical Spectrum of Late-onset Pompe Disease: Dilated Arteriopathy Involving the Thoracic Aorta, a Novel Vascular Phenotype Uncovered

Molecular Genetics and Metabolism. Aug, 2011  |  Pubmed ID: 21605996

Cerebro-vascular arteriopathy has been reported in late-onset Pompe disease (LOPD). Evidence of increased aortic stiffness in some patients and smooth muscle involvement in LOPD raises the possibility of aortic involvement. Our aim was to determine if aortic arteriopathy may be a complication of LOPD.

Colorectal Cancer Screening Among Ethnically Diverse, Low-income Patients: a Randomized Controlled Trial

Archives of Internal Medicine. May, 2011  |  Pubmed ID: 21606094

Patient navigators may increase colorectal cancer (CRC) screening rates among adults in underserved communities, but prior randomized trials have been small or conducted at single sites and have not included substantial numbers of Haitian Creole-speaking or Portuguese-speaking patients.

Diabetic Ketoacidosis Presenting with Acute Pancreatitis and Visceral Vein Thrombosis

Tennessee Medicine : Journal of the Tennessee Medical Association. May, 2011  |  Pubmed ID: 21608311

Abdominal pain is a frequent manifestation in patients presenting with Diabetic Ketoacidosis (DKA). Usually it is attributed to severe metabolic acidosis but it can be due to underlying abdominal pathologies (i.e., pancreatitis, appendicitis). We report a case of a 19-year-old female who presented with DKA and severe abdominal pain and was found on further examination to have underlying pancreatitis and visceral vein thrombosis. The patient improved with treatment for the mentioned co-morbidities, including anticoagulation.

Intercellular Cancer Collisions Generate an Ejected Crystal Comet Tail Effect with Fractal Interface Embryoid Body Reassembly Transformation

Cancer Management and Research. 2011  |  Pubmed ID: 21625398

We have documented self-assembled geometric triangular chiral crystal complexes (GTCHC) and a framework of collagen vascular invariant geometric attractors in cancer tissues. This article shows how this system evolves in time. These structures are incorporated together and evolve in different ways. When the geometric core is stable, and the tissue architecture collapses, fragmented components emerge, which reveal a hidden interior identifying how each molecule is reassembled into the original mold, using one common connection, ie, a fractal self-similarity that guided the system from the beginning. GTCHC complexes generate ejected crystal comet tail effects and produce strange helicity states that arise in the form of spin domain interactions. As the crystal growth vibration stage progresses, biofractal echo images converge in a master-built construction of embryoid bodies with enolase-selective immunopositivity in relation to clusters of triangular chiral cell organization. In our electro-optic collision model, we were able to predict and replicate all the characteristics of this complex geometry that connects a physical phenomenon with the signal patterns that generate biologic chaos. Intrinsically, fractal geometry makes spatial correction errors embrace the chaotic system in a way that permits new structures to emerge, and as a result, an ordered self-assembly of embryoid bodies with neural differentiation at the final stage of cancer development is a predictable process. We hope that further investigation of these structures will lead not only to a new way of thinking about physics and biology, but also to a rewarding area in cancer research.

Changing Trends in the Epidemiology of Pyogenic Vertebral Osteomyelitis: the Impact of Cases with No Microbiologic Diagnosis

Seminars in Arthritis and Rheumatism. Oct, 2011  |  Pubmed ID: 21665246

The observed higher incidence of pyogenic vertebral osteomyelitis (PVO) may entail an increasing number of patients with no microbiologic diagnosis. The true incidence of these cases, how exhaustive the etiologic diagnostic efforts must be, and the usefulness of an empirical antibiotic therapy are not well defined.

Inhibition of Protein Kinase C Decreases Sensitivity of GABA Receptor Subtype to Fipronil Insecticide in Insect Neurosecretory Cells

Neurotoxicology. Dec, 2011  |  Pubmed ID: 21684305

Phosphorylation by serine/threonine kinases has been described as a new mechanism for regulating the effects of insecticides on insect neuronal receptors and channels. Although insect GABA receptors are commercially important targets for insecticides (e.g. fipronil), their modulation by kinases is poorly understood and the influence of phosphorylation on insecticide sensitivity is unknown. Using the whole-cell patch-clamp technique, we investigated the modulatory effect of PKC and CaMKinase II on GABA receptor subtypes (GABAR1 and GABAR2) in DUM neurons isolated from the terminal abdominal ganglion (TAG) of Periplaneta americana. Chloride currents through GABAR2 were selectively abolished by PMA and PDBu (the PKC activators) and potentiated by Gö6983, an inhibitor of PKC. Furthermore, using KN-62, a specific CaMKinase II inhibitor, we demonstrated that CaMKinase II activation was also involved in the regulation of GABAR2 function. In addition, using CdCl(2) (the calcium channel blocker) and LOE-908, a blocker of TRPγ, we revealed that calcium influx through TRPγ played an important role in kinase activations. Comparative studies performed with CACA, a selective agonist of GABAR1 in DUM neurons confirmed the involvement of these kinases in the specific regulation of GABAR2. Furthermore, our study reported that GABAR1 was less sensitive than GABAR2 to fipronil. This was demonstrated by the biphasic concentration-response curve and the current-voltage relationship established with both GABA and CACA. Finally, we demonstrated that GABAR2 was 10-fold less sensitive to fipronil following inhibition of PKC, whereas inhibition of CaMKinase II did not alter the effect of fipronil.

Nitrite As a Mediator of Ischemic Preconditioning and Cytoprotection

Nitric Oxide : Biology and Chemistry / Official Journal of the Nitric Oxide Society. Aug, 2011  |  Pubmed ID: 21277988

Ischemia/reperfusion (IR) injury is a central component in the pathogenesis of several diseases and is a leading cause of morbidity and mortality in the western world. Subcellularly, mitochondrial dysfunction, characterized by depletion of ATP, calcium-induced opening of the mitochondrial permeability transition pore, and exacerbated reactive oxygen species (ROS) formation, plays an integral role in the progression of IR injury. Nitric oxide (NO) and more recently nitrite (NO(2)(-)) are known to modulate mitochondrial function, mediate cytoprotection after IR and have been implicated in the signaling of the highly protective ischemic preconditioning (IPC) program. Here, we review what is known about the role of NO and nitrite in cytoprotection after IR and consider the putative role of nitrite in IPC. Focus is placed on the potential cytoprotective mechanisms involving NO and nitrite-dependent modulation of mitochondrial function.

Response of Holm Oak (Quercus Ilex Subsp. Ballota) and Mastic Shrub (Pistacia Lentiscus L.) Seedlings to High Concentrations of Cd and Tl in the Rhizosphere

Chemosphere. May, 2011  |  Pubmed ID: 21281955

The impairment of root growth and photosynthetical functioning are the main impacts of trace elements on woody plant seedlings. In this work, we assessed the response of Holm oak (Quercusilex subsp. ballota) and mastic shrub (Pistacia lentiscus) seedlings to high concentrations of Cd and Tl in the rhizosphere. These are non-essential trace elements, with a potential high mobility in the soil-plant system. Seedlings of these species are frequently used in the afforestation of degraded soils in mining areas. Plants were exposed to different levels of Cd (20, 80 and 200 mg L(-1)) and Tl (2, 10 and 20 mg L(-1)) in a sand culture. Biomass allocation, growth rates, chlorophyll fluorescence and gas exchange were studied. Both metals affected root biomass. Cadmium produced an increase in the root mass ratio and a decrease in the specific leaf area of the plants in oak seedlings, while Tl did not provoke such response. Mastic plants were more sensitive to Tl and Cd than oak plants. Between elements, Tl provoked more severe toxic effects in the plants, affecting the antennae complexes and reaction centers of the photosystem II. Both elements decreased net assimilation rates (down to a 20% of the control plants) and stomatal conductance (5-10% of the values for the control plants). Cadmium was highly retained in the roots of both species, while Tl was highly translocated into the leaves. In general, Holm oak showed a higher tolerance for Cd than for Tl, and a higher resistance to both metals than mastic shrub, due to a high capacity for Cd retention at the root level. However, such accumulation in roots may induce water stress in the seedling exposed to Cd.

Functional Significance of Vitamin D Receptor FokI Polymorphism in Human Breast Cancer Cells

PloS One. 2011  |  Pubmed ID: 21283672

The FokI vitamin D receptor (VDR) polymorphism results in different translation initiation sites on VDR. In the VDRff variant, initiation of translation occurs at the first ATG site, giving rise to a full length VDR protein of 427 amino acids. Conversely, in the VDRFF variant, translation begins at the second ATG site, resulting in a truncated protein with three less amino acids. Epidemiological studies have paradoxically implicated this polymorphism with increased breast cancer risk. 1α,25 (OH)(2)D(3), the active metabolite of vitamin D, is known to inhibit cell proliferation, induce apoptosis and potentiate differentiation in human breast cancer cells. It is well documented that 1α,25 (OH)(2)D(3) downregulates estrogen receptor α expression and inhibits estrogen mediated signaling in these cells. The functional significance of the VDR FokI polymorphism in vitamin D action is undefined.

Occurrence of Cleft-palate and Alteration of Tgf-β(3) Expression and the Mechanisms Leading to Palatal Fusion in Mice Following Dietary Folic-acid Deficiency

Cells, Tissues, Organs. 2011  |  Pubmed ID: 21293104

Folic acid (FA) is essential for numerous bodily functions. Its decrease during pregnancy has been associated with an increased risk of congenital malformations in the progeny. The relationship between FA deficiency and the appearance of cleft palate (CP) is controversial, and little information exists on a possible effect of FA on palate development. We investigated the effect of a 2-8 weeks' induced FA deficiency in female mice on the development of CP in their progeny as well as the mechanisms leading to palatal fusion, i.e. cell proliferation, cell death, and palatal-shelf adhesion and fusion. We showed that an 8 weeks' maternal FA deficiency caused complete CP in the fetuses although a 2 weeks' maternal FA deficiency was enough to alter all the mechanisms analyzed. Since transforming growth factor-β(3) (TGF-β(3)) is crucial for palatal fusion and since most of the mechanisms impaired by FA deficiency were also observed in the palates of Tgf-β(3)null mutant mice, we investigated the presence of TGF-β(3) mRNA, its protein and phospho-SMAD2 in FA-deficient (FAD) mouse palates. Our results evidenced a large reduction in Tgf-β(3) expression in palates of embryos of dams fed an FAD diet for 8 weeks; Tgf-β(3) expression was less reduced in palates of embryos of dams fed an FAD diet for 2 weeks. Addition of TGF-β(3) to palatal-shelf cultures of embryos of dams fed an FAD diet for 2 weeks normalized all the altered mechanisms. Thus, an insufficient folate status may be a risk factor for the development of CP in mice, and exogenous TGF-β(3) compensates this deficit in vitro.

Racial Disparities in Health Literacy and Access to Care Among Patients with Heart Failure

Journal of Cardiac Failure. Feb, 2011  |  Pubmed ID: 21300301

Previous work has shown that there is a higher frequency of hospitalizations among black heart failure patients relative to white heart failure patients. We sought to determine whether racial differences exist in health literacy and access to outpatient medical care, and to identify factors associated with these differences.

Genome-wide Significant Association Between a Sequence Variant at 15q15.2 and Lung Cancer Risk

Cancer Research. Feb, 2011  |  Pubmed ID: 21303977

Genome-wide association studies (GWAS) have identified 3 genomic regions, at 15q24-25.1, 5p15.33, and 6p21.33, which associate with the risk of lung cancer. Large meta-analyses of GWA data have failed to find additional associations of genome-wide significance. In this study, we sought to confirm 7 variants with suggestive association to lung cancer (P < 10(-5)) in a recently published meta-analysis. In a GWA dataset of 1,447 lung cancer cases and 36,256 controls in Iceland, 3 correlated variants on 15q15.2 (rs504417, rs11853991, and rs748404) showed a significant association with lung cancer, whereas rs4254535 on 2p14, rs1530057 on 3p24.1, rs6438347 on 3q13.31, and rs1926203 on 10q23.31 did not. The most significant variant, rs748404, was genotyped in an additional 1,299 lung cancer cases and 4,102 controls from the Netherlands, Spain, and the United States and the results combined with published GWAS data. In this analysis, the T allele of rs748404 reached genome-wide significance (OR = 1.15, P = 1.1 × 10(-9)). Another variant at the same locus, rs12050604, showed association with lung cancer (OR = 1.09, 3.6 × 10(-6)) and remained significant after adjustment for rs748404 and vice versa. rs748404 is located 140 kb centromeric of the TP53BP1 gene that has been implicated in lung cancer risk. Two fully correlated, nonsynonymous coding variants in TP53BP1, rs2602141 (Q1136K) and rs560191 (E353D) showed association with lung cancer in our sample set; however, this association did not remain significant after adjustment for rs748404. Our data show that 1 or more lung cancer risk variants of genome-wide significance and distinct from the coding variants in TP53BP1 are located at 15q15.2.

Deep Oxidation of Pollutants Using Gold Deposited on a High Surface Area Cobalt Oxide Prepared by a Nanocasting Route

Journal of Hazardous Materials. Mar, 2011  |  Pubmed ID: 21315508

Gold deposited on a cobalt oxide with high surface area (138 m(2)g(-1)), obtained through a nanocasting route using a siliceous KIT-6 mesoporous material as a hard template, has demonstrated high activity for the total oxidation of propane and toluene, and ambient temperature CO oxidation. The addition of gold promotes the activity when compared to a gold-free Co(3)O(4) catalyst prepared using the same nanocasting technique. The enhanced catalytic activity when gold is present has been explained for the deep oxidation of propane and toluene in terms of the improved reducibility of cobalt oxide when gold is added, rather than to the intrinsic activity of metallic gold particles. The improved behaviour for CO oxidation has been linked to the simultaneous presence of Au(δ+) and Au°.

Valorisation of Forestry Waste by Pyrolysis in an Auger Reactor

Waste Management (New York, N.Y.). Jun, 2011  |  Pubmed ID: 21333517

Pyrolysis of forestry waste has been carried out in an auger reactor to study the influence of operational variables on the reactor performance and the properties of the related products. Pine woodchips were used for the first time as raw material and fed continuously into the reactor. Ten experiments were carried out under inert atmosphere at: (i) different reaction temperature (1073, 973, 873, 823 and 773 K); (ii) different solid residence time (5, 3, 2 and 1.5 min); and (iii) different biomass flow rate (3.9, 4.8 and 6.9 kg/h). Results show that the greatest yields for liquid production (59%) and optimum product characterisation were obtained at the lowest temperature studied (773 K) and applying solid residence times longer than 2 min. Regarding bio-oil properties, GC/MS qualitative identification show that the most abundant compounds are volatile polar compounds, phenols and benzenediols; and very few differences can be observed among the samples regardless of the pyrolysis operating conditions. On the whole, experimental results demonstrate that complete reaction of forest woodchips can be achieved in an auger reactor in most of the experimental conditions tested. Moreover, this study presents the initial steps for the future scaling up of the auger reactor with the aim of converting it into a mobile plant which will be able to remotely process biomass such as energy crops, forestry and agricultural wastes to obtain bio-oil that, in turn, can be used as energy vector to avoid high transport costs.

Cryptogenic Stroke in Young Patients: Long-term Prognosis and Recurrence

Neurología (Barcelona, Spain). Jun, 2011  |  Pubmed ID: 21354670

Around 40% of strokes in young people are labelled as infarcts of undetermined cause. The aim of this study was to determine the image characteristics, the long-term functional outcome and recurrence after cryptogenic ischaemic stroke.

Physiological Role and Potential Clinical Interest of Mycobacterial Pigments

IUBMB Life. Feb, 2011  |  Pubmed ID: 21360635

The production of pigments by bacterial colonies has sparked interest among bacteriologists since the 19th century, whether for taxonomy or, in the case of carotenoids for their association with antibiotics resistance. Mycobacteria have gained a very special place in the bacterial world due to their clinical importance. Alone, Mycobacterium tuberculosis is responsible for about two million deaths annually worldwide making tuberculosis one of the most influential diseases in the history of mankind. Almost half of the Nontuberculous Mycobacteria species identified are associated with opportunistic infections in animals and humans. Mycobacterial pigmentary characteristics started to be documented about 80 years ago; but to date, their main use has been only for limited taxonomic and identification purposes. While mycobacterial pigments, especially carotenoids have been clearly associated with cellular photoprotection and survival, the regulation of their production and their physiological role have been largely unstudied. Recent advances in deciphering mycobacterial genomes and characterization of carotenoid synthesis genes, combined with an urgent need for innovative approaches to understand Mycobacterium tuberculosis pathogenic properties open new avenues for exciting research opportunities that might lead to new therapeutic strategies against a devastating secular disease.

Variation in Conservation of the Cluster for Biosynthesis of the Phytotoxin Phaseolotoxin in Pseudomonas Syringae Suggests at Least Two Events of Horizontal Acquisition

Research in Microbiology. Apr, 2011  |  Pubmed ID: 21187143

Certain strains of Pseudomonas syringae pathovars phaseolicola and actinidiae and P. syringae pv. syringae strain CFBP3388 produce the chlorosis-inducing phytotoxin phaseolotoxin, which inhibits biosynthesis of arginine and polyamines. The 25 kb Pht cluster, responsible for phaseolotoxin biosynthesis, is included in a putative pathogenicity island that is nearly identical in selected strains of the pathovars phaseolicola and actinidiae, suggesting that it has been recently acquired by horizontal transfer. The history of pathogenicity islands is pivotal for our understanding of the evolution of virulence in plant pathogenic bacteria; nevertheless, our knowledge of the origins, biology and genetics of this island is currently rather limited. The aim of this work was to explore the conservation of phaseolotoxin biosynthesis genes in a broader collection of isolates and in strain CFBP3388, in order to better understand its evolution and gene dynamics. PCR, hybridization and sequence analysis showed that the island is highly conserved among a diversity of strains of pathovars phaseolicola and actinidiae, suggesting that it was acquired only once by each pathovar. Strain CFBP3388 contained DNA homologous to the Pht cluster, and an insertional mutant in the regulatory gene phtL did not synthesize the toxin. A 6.5 kb fragment from strain CFBP3388 was syntenic to the Pht cluster, but showed nucleotide identity of only 85.3%. This contrasts with an identity higher than 99.8% among clusters of pathovars phaseolicola and actinidiae, in spite of the fact that pv. syringae is phylogenetically closer to pv. phaseolicola. In addition, strain CFBP3388 lacked the four integrases that are putatively responsible for the mobility of the pathogenicity island. These results indicate that genes for the biosynthesis of phaseolotoxin have a complex evolutionary history and were acquired by pathovars of P. syringae at least twice during evolution.

Sapotexanthin, an A-provitamin Carotenoid from Red Mamey (Pouteria Sapota)

Journal of Natural Products. Feb, 2011  |  Pubmed ID: 21214217

From the ripe fruits of red mamey (Pouteria sapota) sapotexanthin, a new carotenoid, was identified as (all-E,5'R)-β,κ-caroten-6'-one.

Evidence for Covert Baculovirus Infections in a Spodoptera Exigua Laboratory Culture

The Journal of General Virology. May, 2011  |  Pubmed ID: 21228125

A laboratory culture of Spodoptera exigua was examined to assess covert (latent or persistent) baculovirus infections and spontaneous disease outbreaks. Two nucleopolyhedrovirus (NPV) species were found to be reactivated from a covert state in a laboratory culture of S. exigua to fully lethal forms. These were identified as S. exigua multinucleopolyhedrovirus (SeMNPV) and Mamestra brassicae NPV (MbNPV) using restriction enzyme analysis of purified viral DNA. Sequence data derived from both overtly and covertly virus-infected insects revealed highly conserved sequences for lef-8, lef-9 and polyhedrin gene sequence (98-100 % nucleotide identity to SeMNPV published sequence). By monitoring spontaneous overt infections and quantifying viral DNA (by quantitative-PCR) in asymptomatic individuals over two generations we identified fluctuating trends in viral DNA levels from covert SeMNPV and MbNPV within an S. exigua host population. Virus levels per insect life stage ranged from 3.51±0.101×10(5) to 0.29±0.036 pg (detection limit at 0.06 pg). Bioassays performed with this culture of larvae showed a differential susceptibility to SeMNPV-like or MbNPV-like viruses, with SeMNPV superinfections being extremely virulent. The data presented has broad implications relating to our understanding of transmission patterns of baculovirus in the environment and the role of covert infections in host-pathogen interaction dynamics.

Light-dependent Gene Regulation in Nonphototrophic Bacteria

Current Opinion in Microbiology. Apr, 2011  |  Pubmed ID: 21239214

Bacteria sense and respond to light, a fundamental environmental factor, by employing highly evolved machineries and mechanisms. Cellular systems exist to harness light energy usefully as in phototrophic bacteria, to combat photo-oxidative damage stemming from the highly reactive species generated on absorption of light energy, and to link the light stimulus to DNA repair, taxis, development, and virulence. Recent findings on the genetic response to light in nonphototrophic bacteria highlight the ingenious transcriptional regulatory mechanisms and the panoply of factors that have evolved to perceive and transmit the signal, and to bring about finely tuned gene expression.

Tuning the Electrochemistry of Re2(6+) Species with Divergent Bicyclic Guanidinate Ligands and by Modification of Axial π Interactions

Inorganic Chemistry. Feb, 2011  |  Pubmed ID: 21250639

Four Re(2)(6+) paddlewheel compounds with equatorial bicyclic guanidinate ligands and two monodentate anions in axial positions show a large change in the metal-metal distance that depends on the bite angle of the ligands and whether there are pi interactions between the dimetal unit and the axial ligands. These processes are accompanied by significant changes in the redox behavior. The two pairs of compounds that have been synthesized are Re(2)(tbn)(4)Cl(2), 1, and Re(2)(tbn)(4)(SO(3)CF(3))(2), 2, as well as Re(2)(tbo)(4)Cl(2), 3, and Re(2)(tbo)(4)(SO(3)CF(3))(2), 4, where tbn is the anion of a bicyclic guanidinate with six- and five-membered rings (1,5,7-triazabicyclo[4.3.0]non-6-ene) and tbo is an analogous species with two five-membered rings (the anion of 1,4,6-triazabicyclo[3.3.0]oct-4-ene). For both 1 and 2 as well as for 3 and 4, the metal-metal distances are shorter for the triflate species than for the chloride analogues because of the π interactions of the Cl with the π bonds of the triply bonded Re(2)(6+) cores compounded by a small but symmetry allowed interaction between the antisymmetric combination of the filled σp orbitals of the chlorine atom and the empty σ* orbital of the metal atoms. In addition there is a significant increase in the Re-Re distance from that in the six/five tbn-membered ring to the five/five-membered tbo species. Electrochemical measurements show two redox processes for each set of compounds corresponding to the uncommon Re(2)(6+) → Re(2)(7+) and Re(2)(7+) → Re(2)(8+) processes, which are strongly affected by the bite angle of the guanidinate ligand as well as the ability of the axial ligands to interact with the π orbitals of the dirhenium unit. For 1 and 3, the first redox couples are at 0.146 and 0.487 V, respectively, while for 2 and 4 these are at 0.430 and 0.698 V, respectively.

E6 Molecular Variants of Human Papillomavirus (HPV) Type 16: an Updated and Unified Criterion for Clustering and Nomenclature

Virology. Feb, 2011  |  Pubmed ID: 21130481

Reports on taxonomic identification of E6/HPV 16 variants, don't have a worldwide, updated and unified criterion for clustering and nomenclature. Our aim was to update the existing criterion and propose a new one for clustering and nomenclature for E6/HPV 16 molecular variants based on the descriptive and comparative analyses of nucleotide sequences. A systematic search of the publications between 1991 and 2010 was carried out in PUBMED and manually. 240 E6/HPV 16 variants were identified. 157 were classified as European (E), 24 as Asian (As), 14 as Asian American (AA), 11 as North American 1 (NA 1), 19 as African 1 (Af 1) and 15 as African 2 (Af 2). Three classes were determined for the E, 3 each for the As, Af 2 and AA branches, 4 classes for the NA 1 and 6 for the Af 1 branch. This study reports our results and proposes an updated criterion for clustering and nomenclature that will be useful for E6 variant identification.

Lipopolysaccharide-induced Intestinal Motility Disturbances Are Mediated by C-Jun NH2-terminal Kinases

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. Apr, 2011  |  Pubmed ID: 21168375

Lipopolysaccharide (LPS) is a causative agent of sepsis. Many alterations, such as intestinal motility disturbances, have been attributed to LPS.

Extracellular Signal-regulated Kinase (ERK) is Involved in LPS-induced Disturbances in Intestinal Motility

Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society. Feb, 2011  |  Pubmed ID: 21087357

Lipopolysaccharide (LPS) is a causative agent of sepsis. A relationship has been described between LPS, free radicals, and cyclooxygenase-2 (COX-2). Here, we investigate the role of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPK) in the effect of LPS on intestinal motility, oxidative stress status, and COX-2 expression.

Effect of Dietary Selenite on Development and Intestinal Absorption in Offspring Rats

Life Sciences. Jan, 2011  |  Pubmed ID: 21062629

The present study aims to compare selenium (Se) status in offspring rats born to selenium-deficient and selenium supplemented dams and to analyse Se's influence on intestinal parameters and the intestinal absorption of selenomethionine (Se-Met).

Methotrexate-induced Subacute Neurotoxicity in a Child with Acute Lymphoblastic Leukemia Carrying Genetic Polymorphisms Related to Folate Homeostasis

American Journal of Hematology. Jan, 2011  |  Pubmed ID: 21064136

Subacute methotrexate neurotoxicity (MTX-NT) may occur days to weeks after systemic or intrathecal (IT) MTX administration and is often manifest by stroke-like symptoms. The pathogenesis of MTX-NT has mainly been associated with cerebral folate homeostasis, but the specific mechanism leading to the development of this complication is mostly unknown and is likely to be multifactorial. Most of studies aimed to determine putative genetic determinants of this syndrome have been focused on the methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism (SNP). However, there are other functional polymorphisms that have also been identified in enzymes and transporters related to MTX and folate homeostasis. In this context, we carried out an extensive genetic analysis through the screening of 21 SNPs in 11 relevant genes in a five-year-old girl with acute lymphoblastic leukemia (ALL) who developed MTX-NT. The analysis revealed the presence of numerous genetic variants that may have accounted for the neurotoxicity observed. We discuss the putative role of MTX pharmacogenetics in the pathogenesis of MTX-NT.

The Immediate Effects of Diacutaneous Fibrolysis on Pain and Mobility in Patients Suffering from Painful Shoulder: a Randomized Placebo-controlled Pilot Study

Clinical Rehabilitation. Apr, 2011  |  Pubmed ID: 21078700

To describe the immediate effects of diacutaneous fibrolysis on pain and mobility in patients suffering from painful shoulder, and to assess the ability of the placebo technique to blind participants to group allocation.

Structure of the Mycobacterium Tuberculosis D-alanine:D-alanine Ligase, a Target of the Antituberculosis Drug D-cycloserine

Antimicrobial Agents and Chemotherapy. Jan, 2011  |  Pubmed ID: 20956591

D-alanine:D-alanine ligase (EC 6.3.2.4; Ddl) catalyzes the ATP-driven ligation of two D-alanine (D-Ala) molecules to form the D-alanyl:D-alanine dipeptide. This molecule is a key building block in peptidoglycan biosynthesis, making Ddl an attractive target for drug development. D-Cycloserine (DCS), an analog of D-Ala and a prototype Ddl inhibitor, has shown promise for the treatment of tuberculosis. Here, we report the crystal structure of Mycobacterium tuberculosis Ddl at a resolution of 2.1 Å. This structure indicates that Ddl is a dimer and consists of three discrete domains; the ligand binding cavity is at the intersection of all three domains and conjoined by several loop regions. The M. tuberculosis apo Ddl structure shows a novel conformation that has not yet been observed in Ddl enzymes from other species. The nucleotide and D-alanine binding pockets are flexible, requiring significant structural rearrangement of the bordering regions for entry and binding of both ATP and D-Ala molecules. Solution affinity and kinetic studies showed that DCS interacts with Ddl in a manner similar to that observed for D-Ala. Each ligand binds to two binding sites that have significant differences in affinity, with the first binding site exhibiting high affinity. DCS inhibits the enzyme, with a 50% inhibitory concentration (IC(50)) of 0.37 mM under standard assay conditions, implicating a preferential and weak inhibition at the second, lower-affinity binding site. Moreover, DCS binding is tighter at higher ATP concentrations. The crystal structure illustrates potential drugable sites that may result in the development of more-effective Ddl inhibitors.

Determination of Carbonyls and Their Sources in Three Sites of the Metropolitan Area of Costa Rica, Central America

Environmental Monitoring and Assessment. Jan, 2012  |  Pubmed ID: 21365442

Ambient levels of carbonyl compounds and their possible sources were studied at three places in the metropolitan area of Costa Rica, including a residential, an industrial, and a commercial downtown area with high vehicular flow, during the periods of April-May and September-December 2009. Fifteen carbonyl compounds were identified in the ambient air, of which acetone was the most abundant carbonyl, followed by formaldehyde and acetaldehyde. Concentrations were highest in rainy season at all sites and lower in dry season. These decreases in concentration are explained by the influences of both photochemical reactions and local meteorological conditions. The strong correlation between C1-C2 and C3 indicated a common origin for these carbonyls. The C1/C2 ratios varied between 0.49 to 1.05, values which can be considered typical of an urban area.

Pasture Composition in a Trace Element-contaminated Area: the Particular Case of Fe and Cd for Grazing Horses

Environmental Monitoring and Assessment. Apr, 2012  |  Pubmed ID: 21573712

Pasture selection by livestock is an essential topic for rangeland management, especially in trace element-contaminated soils. We have studied the composition (nutrients and trace elements) of a grass-based diet from soils affected by a mine spill at different growth stages (October 2008 to May 2009). A diet based on other plants (mainly Compositae species) was also studied (May 2009) for comparison. Faeces and mane hair of horses feeding on these pastures were also analysed. Micronutrient (Cu, Fe, Mn and Zn) and potentially toxic trace element (As, Cd, Pb, Tl) concentrations were below the maximum tolerable levels (MTL) for horses, except for Fe (at early growth of pastures) and Cd (in the diet based on 'other' plants). Values of potential ingestion of Fe by horses were higher than 10 mg kg body weight(- 1) day(- 1). Cadmium concentrations in some pasture samples (those composed of Compositae species) were higher than 3 mg kg(- 1). Potential toxicity of such Cd levels in pastures is uncertain, since a high disparity of criteria about MTL by cattle exists (between 0.5 and 10 mg kg(- 1) diet). Nutrient concentrations were adequate for horses, which could counteract possible harmful effects derived from trace element ingestion. The analyses of excreta and mane hair point to the low risk of toxicity derived from the consumption of these contaminated pastures. However, the ingestion of regenerating pastures (autumnal samples) should be avoided due to the greater risk of ingestion of contaminated soil attached to the plant material. Management of these pastures by grazing requires periodic monitoring. Special attention should be given to Fe and particularly Cd (non-essential element) which accumulates in animal organs, where it could provoke uncertain long-term effects.

Regulation of CYP24 Splicing by 1,25-dihydroxyvitamin D₃ in Human Colon Cancer Cells

The Journal of Endocrinology. Feb, 2012  |  Pubmed ID: 22068926

CYP24 is a well-established vitamin D receptor (VDR) target gene. The active VDR ligand 1,25(OH)₂D₃ regulates its own catabolism by increasing CYP24 expression. It is well known that in the presence of 1,25(OH)₂D₃, VDR binds to VDREs in the promoter region of CYP24 and initiates CYP24 transcription. However, little is known about the role of 1,25(OH)₂D₃ in the posttranscriptional modulation of CYP24. In this study, we investigated the functional significance of 1,25(OH)₂D₃ in CYP24 RNA splicing in colon cancer cells. Using RT-PCR, we found that 1,25(OH)₂D₃ actively induces CYP24 splicing in a time-dependent manner and CYP24 splicing pattern could be cell type or tissue specific. The induction of RNA splicing by 1,25(OH)₂D₃ was mainly CYP24 selective. Treatment of cells with parathyroid hormone inhibited basal CYP24 splicing, but failed to inhibit 1,25(OH)₂D₃-induced CYP24 splicing. Further experiments demonstrated that new RNA synthesis was required for the induction of CYP24 splicing by vitamin D. In addition, alteration of multiple signaling pathways also affected CYP24 splicing and cellular sensitivity in response to vitamin D appeared to correlate with the induction of CYP24 splicing. These results suggest that 1,25(OH)₂D₃ not only regulates CYP24 transcription, but also plays an important role in posttranscriptional modulation of CYP24 by inducing its splicing. Our findings reveal an additional regulatory step that makes the vitamin D mediated action more prompt and efficient.

Fatal Bacillary Angiomatosis Mimicking an Infiltrative Vascular Tumour in the Immune Restoration Phase of an HIV-infected Patient

Antiviral Therapy. 2012  |  Pubmed ID: 22293094

Bacillary angiomatosis mainly affects the HIV-infected population. Information is limited on the evolution of bacillary angiomatosis during immune restoration following initiation of HAART. We report an unusual case of fatal Bartonella quintana bacillary angiomatosis occurring in an HIV-infected man during the immune restoration phase.

Phenotype Characterization of Embryoid Body Structures Generated by a Crystal Comet Effect Tail in an Intercellular Cancer Collision Scenario

Cancer Management and Research. 2012  |  Pubmed ID: 22346365

Cancer is, by definition, the uncontrolled growth of autonomous cells that eventually destroy adjacent tissues and generate architectural disorder. However, this concept cannot be totally true. In three well documented studies, we have demonstrated that cancer tissues produce order zones that evolve over time and generate embryoid body structures in a space-time interval. The authors decided to revise the macroscopic and microscopic material in well-developed malignant tumors in which embryoid bodies were identified to determine the phenotype characterization that serves as a guideline for easy recognition. The factors responsible for this morphogenesis are physical, bioelectric, and magnetic susceptibilities produced by crystals that act as molecular designers for the topographic gradients that guide the surrounding silhouette and establish tissue head-tail positional identities. The structures are located in amniotic-like cavities and show characteristic somite-like embryologic segmentation. Immunophenotypic study has demonstrated exclusion factor positional identity in relation to enolase-immunopositive expression of embryoid body and human chorionic gonadotropin immunopositivity exclusion factor expression in the surrounding tissues. The significance of these observations is that they can also be predicted by experimental image data collected by the Large Hadron Collider (LHC) accelerator at the European Organization for Nuclear Research, in which two-beam subatomic collision particles in the resulting debris show hyperorder domains similar to those identified by us in intercellular cancer collisions. Our findings suggest that we are dealing with true reverse biologic system information in an activated collective cancer stem cell memory, in which physics participates in the elaboration of geometric complexes and chiral biomolecules that serve to build bodies with embryoid print as it develops during gestation. Reversal mechanisms in biology are intimately linked with DNA repair. Further genotype studies must be carried out to determine whether the subproducts of these structures can be used in novel strategies to treat cancer.

Consensus of the Spanish Society of Radiation Oncology (SEOR) Brachytherapy Group on Brachytherapy in Breast Cancer

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. Mar, 2012  |  Pubmed ID: 22374420

Breast cancer is the most frequent neoplasia in women. Randomized studies which compare mastectomy with conservative treatment show no differences in global survival. In cases in which conservative surgery is performed, breast radiation therapy and boost reduces the rate of local recurrence. On March 2010, the 8th Consensus Meeting of the Spanish Society for Radiation Oncology (SEOR) Brachytherapy Group was held in Madrid about «Treatment of Breast Cancer with Brachytherapy». In this article we presented the conclusions about brachytherapy boost, Partial breast irradiation and clinical dosimetry.

Ferret-transmissible Influenza A(H5N1) Virus: Let Us Err on the Side of Caution

MBio. 2012  |  Pubmed ID: 22396481

Mutations in FGFR3 and PIK3CA, Singly or Combined with RAS and AKT1, Are Associated with AKT but Not with MAPK Pathway Activation in Urothelial Bladder Cancer

Human Pathology. Mar, 2012  |  Pubmed ID: 22417847

Different members of the phosphoinositide 3 kinase - serine threonine protein kinase (PI3K-AKT) pathway are altered in bladder cancer. Fibroblast growth factor receptor 3 (FGFR3) mutations characterize the low-grade tumors, and RAS genes are mutated in approximately 13% of all bladder tumors. Interestingly, a percentage of bladder tumors have alterations in more than 1 PI3K-AKT or rat sarcoma viral oncogene homolog-RAF mitogen activated protein kinase (RAS-MAPK) pathway gene or their upstream regulators, but some combinations are mutually exclusive. We analyzed mutations in FGFR3, phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in 88 urothelial cell carcinomas and the immunohistochemical expression of phospho-v-akt murine thymoma viral oncogene homolog (AKT) and mitogen-activated protein kinase 1 and 2 (pERK1/2) in 80 and 77 urothelial cell carcinomas, respectively. Approximately 43% and 20.5% of tumors presented 1 and 2 mutated genes, respectively. FGFR3 mutations were more frequent alone, whereas PIK3CA mutations were associated with another mutated gene (FGFR3 and KRAS). Overall, mutated FGFR3 (FGFR3(mut)) and mutated FGFR3 (FGFR3(mut))-mutated PIK3CA (PIK3CA(mut)) genotypes were associated with low-grade bladder tumors and mutated PIK3CA (PIK3CA(mut))-mutated KRAS (KRAS(mut)) and mutated AKT1 (AKT1(mut)) were only present in high-grade tumors. There are no mutated FGFR3 (FGFR3(mut))-mutated RAS (RAS(mut)) nor mutated PIK3CA (PIK3CA(mut))-mutated AKT1 (AKT1(mut)) combinations. Fifty percent and 56% of tumors showed high levels of pAKT and pERK1/2, respectively. High levels of pAKT were associated with total mutations, FGFR3(mut), and PIK3CA(mut) tumors but not with tumor grade or stage. Wild-type tumors presented significantly higher pERK1/2 expression. Mutations in FGFR3 and FGFR3-PIK3CA but not single PIK3CA mutations characterize low-grade bladder tumors. Single FGFR3 or PIK3CA mutations and the different mutation combinations FGFR3-PIK3CA/AKT1 and PIK3CA-RAS can activate the AKT but not the MAPK pathway. Other genes different from FGFR3 may be related with the pERK activation in bladder tumors.

The CD47-signal Regulatory Protein Alpha (SIRPa) Interaction is a Therapeutic Target for Human Solid Tumors

Proceedings of the National Academy of Sciences of the United States of America. Mar, 2012  |  Pubmed ID: 22451913

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.

[Morphological Evidence of Hybridization Between Ramphocelus Flammigerus Subspecies (Passeriformes: Thraupidae) in Colombia]

Revista De Biología Tropical. Mar, 2012  |  Pubmed ID: 22458210

Habitat modifications such as deforestation and the increase of agricultural activities, have led to uncommon faunal interactions. In Colombia, this condition have caused the secondary contact of subspecies of Ramphocelus flammigerus populations from Cauca valley and the Pacific coast; and some specimens with rumps of intermediate colors of the subspecies have been found and are thought as hybrids. The objective of this study was to assess the presence of morphological evidence that may suggest hybridization and may explain the origin of individuals with intermediate coloration. We predict that if subspecies hybridize, they will be more similar in morphology when coexisting than when separated. Alternatively, coexisting subspecies might diverge in sympatry, because of selection to reduce competition for resources (character displacement). For this, a survey in 15 localities was undertaken: 10 allopatric areas (five for each subspecies), and five sympatric areas. Mist nets were used to capture individuals and a total of seven morphological characters were measured. To identify the patterns of morphological variation, we compared morphology of subspecies, sympatric and allopatric populations and individuals of intermediate colors. Consequently, we performed discriminant analysis and test for differences between groups by using 95% confidence intervals for log-ratio tests. A total of 112 individuals were captured (46 intermediate-colored individuals, 20 R. f. flammigerus, and 46 R.f. icteronotus. Discriminant analyses showed that subspecies were well differentiated, and intermediate individuals overlapped with them. Log-ratio test, based on Mahalanobis distances, showed that intermediate individuals were morphologically more similar to both subspecies than subspecies themselves. In addition, log-ratio tests showed that subspecies sympatric populations were similar but allopatric ones were different, and that individuals of intermediate colors were more similar to sympatric than to allopatric populations of the two subspecies. Therefore, morphological evidence supports the predictions of a hybridization hypothesis among the subspecies of R. flammigerus. In conclusion, the analysis of morphological variation in R. flammigerus suggests that hybridization between subspecies is occurring and that a process of genetic introgression is probably in progress.

Influence of Pill Burden and Drug Cost on Renal Function After Transplantation

Pharmacotherapy. Mar, 2012  |  Pubmed ID: 22467382

STUDY OBJECTIVE: To determine the influence of pill burden and drug cost on outcomes after renal transplantation. DESIGN: Retrospective medical record review. SETTING: Kidney and pancreas transplantation center. PATIENTS: Sixty-eight adults who underwent kidney or kidney-pancreas transplantation during 2007. MEASUREMENTS AND MAIN RESULTS: The median pretransplantation pill burden was 15 pills/day, which increased to 25 pills/day at 1 month after transplantation and returned to 16 pills/day by 1 year after transplantation. Pretransplantation pill burden was lower than the burden at 1, 3, 6, 12, and 24 months after transplantation (p<0.05). The mean pretransplantation drug cost of $1918/month was lower than the cost at 1 month after transplantation ($2564/mo, p=0.04) but was similar thereafter. Higher pretransplantation pill burden was associated with increased serum creatinine concentration at 6 months after transplantation (r=0.288, p=0.017). Higher pill burdens at 1 month (r=0.364, p=0.002), 3 months (r=0.332, p=0.006), and 6 months (r=0.374, p=0.002) were associated with increased 3-month serum creatinine concentration. Higher drug costs were associated with increased serum creatinine concentrations throughout the study. CONCLUSION: Higher pretransplantation pill burden and higher drug cost may be associated with poor renal function after transplantation. Further study addressing factors associated with nonadherence is needed.

High Activity Mesoporous Copper Doped Cerium Oxide Catalysts for the Total Oxidation of Polyaromatic Hydrocarbon Pollutants

Chemical Communications (Cambridge, England). Apr, 2012  |  Pubmed ID: 22473462

The doping of mesoporous ceria with copper significantly enhances activity for naphthalene total oxidation, the enhanced performance is controlled by the increased concentration of surface oxygen defects.

Selenium or Selenium Plus Folic Acid-Supplemented Diets Ameliorate Renal Oxidation in Ethanol-Exposed Pups

Alcoholism, Clinical and Experimental Research. Apr, 2012  |  Pubmed ID: 22486362

BACKGROUND: Ethanol (EtOH) exposure during gestation and lactation induces an oxidative stress in offspring. In kidney, the oxidative damage is the primary pathway to alcohol-induced injury. In this study, we have demonstrated that a diet supplemented with selenium (Se) (0.5 ppm) or with Se (0.5 ppm) + folic acid (8 ppm) administered to EtOH-exposed (20% v/v) dams during gestation and lactation prevents the oxidative EtOH-provoked effects in their offspring's kidneys. METHODS: All the studies were performed on 21-day-old pups. Serum, urine, and kidney Se levels were assessed by graphite-furnace atomic absorption spectrometry. Se and creatinine clearance, antioxidant enzyme activities, and lipid and protein peroxidation were determined by a spectrophotometric method in kidney. RESULTS: Dietary supplementation treatments used could not improve the glomerular filtration function altered by EtOH exposure during gestation and lactation; however, they did improve renal Se deposits, renal development, and renal protein content while decreasing lipid and protein oxidation and modifying antioxidant enzymes' activity. CONCLUSIONS: Se or Se + folic acid supplementations improve renal development and protein content and modify antioxidant enzymes' activity, decreasing lipid and protein oxidation after EtOH exposure. In this context, a double-supplemented diet appears to reduce protein peroxidation more efficiently than the Se-only-supplemented one, probably via superoxide dismutase and catalase.

Estrogen Receptor-β Protects Against Colitis-associated Neoplasia in Mice

International Journal of Cancer. Journal International Du Cancer. Apr, 2012  |  Pubmed ID: 22488198

Estrogen receptor-beta (ERβ) has been suggested to exert anti-inflammatory and anti-tumorigenic effects in the colon, providing a translational potential to prevent and/or treat inflammatory bowel disease (IBD) and its progression to colitis-associated colorectal cancer (CAC). However, the specific direct role of ERβ in CAC has not yet been tested. We assessed the effects of ERβ deficiency in the azoxymethane (AOM)/dextran sodium sulfate(DSS)-induced CAC model using ERβ knockout (βERKO) mice and wild-type (WT) littermates. These mice were injected with AOM followed by one week of DSS treatment, and sacrificed on weeks 9 or 16. βERKO mice developed more severe clinical colitis compared to WT mice, as evidenced by significantly higher disease activity index after DSS treatment, weight to length ratio of the colons, inflammation score, and grade of dysplasia. ERβ-deficient colons presented greater number and size of polyps at weeks 9 and 16, respectively, and were characterized by a significant increase in interleukin (IL)-6, IL-17, tumor necrosis factor alpha, and interferon-gamma mRNA levels. Furthermore, higher protein expression levels of nuclear factor-kappa B, inducible nitric oxide synthase, β-catenin, proliferating cell nuclear antigen, mucin-1, and significantly lower caveolin-1 and mucin-2 protein levels were shown in βERKO mice compared to WT mice. These data suggested a possible anti-inflammatory and anti-neoplastic mechanism of action of ERβ in CAC. These results demonstrate for the first time that ERβ provides protection in the AOM/DSS-induced CAC model in mice, suggesting a preventive and/or therapeutic potential for the use of ERβ-selective agonists in IBD. © 2012 Wiley-Liss, Inc.

COL1A1 Association and Otosclerosis: A Meta-analysis

American Journal of Medical Genetics. Part A. May, 2012  |  Pubmed ID: 22489040

Otosclerosis is a disease of abnormal bone remodeling in the human otic capsule that can lead to progressive hearing loss. Little of the underlying disease etiology has been elucidated thus far, although several studies have suggested that COL1A1 may play a role based on its importance in bone metabolism and other diseases like osteoporosis and osteogenesis imperfecta. Genetic association studies between COL1A1 and otosclerosis, however, have been contradictory. To resolve this issue, we studied a large Belgian-Dutch and a Swiss population for a genetic association between COL1A1 and otosclerosis and additionally performed a meta-analysis to investigate the overall genetic effect of COL1A1 on all otosclerosis populations studied to date. We found a significant association both in the Belgian-Dutch population and in the meta-analysis. In aggregate, our analysis supports evidence for an association between COL1A1 and otosclerosis although effect sizes of the variants reported in the initial studies are likely to be an overestimate of true effect sizes. © 2012 Wiley Periodicals, Inc.

Comparison of HIV-1 Resistance Profiles in Plasma RNA Versus PBMC DNA in Heavily Treated Patients in Honduras, a Resource-limited Country

International Journal of Molecular Epidemiology and Genetics. 2012  |  Pubmed ID: 22493752

The World Health Organization currently does not recommend the use of dried blood spot specimens for drug resistance testing in patients undergoing antiretroviral therapy (ART). Therefore, HIV-1 resistance testing using peripheral blood mononuclear cells (PBMCs) may be of value in resource-limited settings. We compared genotypic resistance profiles in plasma and PBMCs from patients failing ART in two cities of Honduras (Tegucigalpa and San Pedro Sula), a resource-limited country. One hundred patients failing ART were randomly selected from a longitudinal patient monitoring cohort. Plasma and PBMC samples without patient identifier were used for genotypic resistance testing. Sequence data were analyzed, resistance profiles were determined and compared using Stanford HIV Drug Resistance Database algorithm. Specimens with concordant resistance profiles between the two compartments were 88% (95% CI: 80.3% - 94.5 %). Nine specimens (12%, 95% CI: 6.5% - 21.3%) had discordant resistance profiles of clinical significance. Logistic regression analyses indicated that patients on triple therapy were 17.24 times more likely to have concordant drug resistance profile than those on non-triple therapies (OR=17.24, 95% CI: 3.48, 83.33), while patients with increasing number of regimens and years on ART have a decreased rate of concordance (OR = 0.59, 95% CI: 0.32, 1.09 and OR = 0.62, 95% CI: 0.43, 0.88), respectively, than those with less number of regimens and years on ART. Our results show high level of concordance between plasma and PBMC resistance profiles, indicating the possibility of using PBMCs for drug resistance testing in resources-limited settings.

Oculopalpebral Borreliosis As an Unusual Manifestation of Lyme Disease

Cornea. Apr, 2012  |  Pubmed ID: 22495033

PURPOSE: To report the case of acrodermatitis chronica atrophicans as an ocularpalpebral manifestation of Lyme borreliosis, with peripheral keratopathy and associated vasculitis. METHODS: Case report. RESULTS: A 16-year-old girl, with a 4-year history of recurrent left eye photophobia, intense redness, and superior eyelid edema, presented with lid erythema, ptosis, superficial venous tortuosity, conjunctival hyperemia, corneal thinning with precipitates, and vascularization. Borrelia burgdorferi was confirmed by immunoblotting. Treatments with doxycycline followed by ceftriaxone were only partially effective. Eyelid biopsy revealed spirochetes and vasculitis with deposition of immunoglobulin G. Oral cefuroxime for 28 days was ineffective. Due to the vasculitis, immunosuppression with azathioprine and topical cyclosporine were given for 4 months. Since then she has been free of flare-ups. CONCLUSIONS: Lyme borreliosis should be considered in patients with recurrent chronic lid edema and associated keratopathy.

Direct Evidence from Electron Paramagnetic Resonance for Additional Configurations in Uncommon Paddlewheel Re(2)(7+) Units Surrounded by an Unsymmetrical Bicyclic Guanidinate

Inorganic Chemistry. Apr, 2012  |  Pubmed ID: 22506487

Three rare compounds have been synthesized and structurally characterized; these species have paddlewheel structures and Re(2)(7+) cores surrounded by four bicyclic guanidinates and two axial ligands along the Re-Re axis. Each possesses a formal bond order of 3.5 and a σ(2)π(4)δ(1) electronic configuration that entails the presence of one unpaired electron for each compound. The guanidinate ligands characterized by having CH(2) entities and a central C(N)(3) unit that joins two cyclic units-one having two fused 6-membered rings (hpp) and the other having a 5- and a 6-membered ring fused together (tbn)-allowed the isolation of [Re(2)(tbn)(4)Cl(2)]PF(6), 1, [Re(2)(tbn)(4)Cl(2)]Cl, 2, and [Re(2)(hpp)(4)(O(3)SCF(3))(2)](O(3)SCF(3)), 3. Because of the larger bite angle of the tbn relative to the hpp ligand, the Re-Re bond distances in 1 and 2 (2.2691(14) and 2.2589(14) Å, respectively) are much longer than that in 3 (2.1804(8) Å). Importantly, electron paramagnetic resonance (EPR) studies at both X-band (∼9.4 GHz) and W-band (112 GHz) in the solid and in frozen solution show unusually low g-values (∼1.75) and the absence of zero-field splitting, providing direct evidence for the presence of one metal-based unpaired electron for both 1 and 3. These spectroscopic data suggest that the unsymmetrical 5-/6-membered ligand leads to the formation of isomers, as shown by significantly broader EPR signals for 1 than for 3, even though both compounds possess what appears to be similar ideal crystallographic axial symmetry on the X-ray time scale.

Highly Dispersed Encapsulated AuPd Nanoparticles on Ordered Mesoporous Carbons for the Direct Synthesis of H(2)O(2) from Molecular Oxygen and Hydrogen

Chemical Communications (Cambridge, England). Apr, 2012  |  Pubmed ID: 22513519

AuPd nanoparticles (<3 nm) have been encapsulated on the pores of a nanostructured CMK-3 carbon prepared by a nanocasting procedure. This material has been shown to be an excellent catalyst for the direct synthesis of hydrogen peroxide from molecular hydrogen and oxygen.

CO₂ Capture from Cement Plants Using Oxyfired Precalcination And/or Calcium Looping

Environmental Science & Technology. Feb, 2012  |  Pubmed ID: 22242605

This paper compares two alternatives to capture CO(2) from cement plants: the first is designed to exploit the material and energy synergies with calcium looping technologies, CaL, and the second implements an oxyfired circulating fluidized bed precalcination step. The necessary mass and heat integration balances for these two options are solved and compared with a common reference cement plant and a cost analysis exercise is carried out. The CaL process applied to the flue gases of a clinker kiln oven is substantially identical to those proposed for similar applications to power plants flue gases. It translates into avoided cost of of 23 $/tCO(2) capturing up to 99% of the total CO(2) emitted in the plant. The avoided cost of an equivalent system with an oxyfired CFBC precalcination only, goes down to 16 $/tCO(2) but only captures 89% of the CO(2) emitted in the plant. Both cases reveal that the application of CaL or oxyfired CFBC for precalcination of CaCO(3) in a cement plant, at scales in the order of 50 MWth (referred to the oxyfired CFB calciner) is an important early opportunity for the development of CaL processes in large scale industrial applications as well as for the development of zero emissions cement plants.

Comparison of Visceral Adipose Tissue Quantification on Water Suppressed and Nonwater-suppressed MRI at 3.0 Tesla

Journal of Magnetic Resonance Imaging : JMRI. Jan, 2012  |  Pubmed ID: 22246813

PURPOSE: To systematically evaluate and compare the performance of water-saturated and nonwater-saturated T1-weighted 3.0 T magnetic resonance imaging (MRI) in the application of visceral adipose tissue (VAT) quantification. MATERIALS AND METHODS: Forty-five patients underwent abdomen MRI using two different sequences at 3.0 T: 1) a traditional T1-weighted gradient echo sequence, and 2) the same sequence with water presaturation to enhance fat and nonfat contrast. VAT amounts from both water-saturated and nonwater-saturated images were quantified with a manual thresholding technique and an automated segmentation method to study quantification variability and consistency of the two imaging techniques. RESULTS: Nonwater-saturated MRI had significantly larger coefficient of variation than water-saturated MRI in the imaging reproducibility study based on 112 slices from seven subjects (11.4% vs. 2.5%, P < 0.0001). VAT volumes measured from the nonwater-saturation MRI sequence had significantly higher variability than those from water-saturation images even when using a manual quantification method based on images from 38 subjects (1.76% vs. 1.08%, P < 0.001). In addition, the VAT volume amounts from nonwater-saturation images and water-saturated images quantified with the automatic and manual quantification methods were statistically consistent. CONCLUSION: Water-saturated MRI sequences at 3.0 T for VAT quantification improve reproducibility and decrease variability compared with nonwater saturated sequences, especially with the use of automatic quantification methods. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.

Characterisation of the Mgo Operon in Pseudomonas Syringae Pv. Syringae UMAF0158 That is Required for Mangotoxin Production

BMC Microbiology. 2012  |  Pubmed ID: 22251433

Mangotoxin is an antimetabolite toxin that is produced by strains of Pseudomonas syringae pv. syringae; mangotoxin-producing strains are primarily isolated from mango tissues with symptoms of bacterial apical necrosis. The toxin is an oligopeptide that inhibits ornithine N-acetyl transferase (OAT), a key enzyme in the biosynthetic pathway of the essential amino acids ornithine and arginine. The involvement of a putative nonribosomal peptide synthetase gene (mgoA) in mangotoxin production and virulence has been reported.

SNP Calling Using Genotype Model Selection on High-throughput Sequencing Data

Bioinformatics (Oxford, England). Mar, 2012  |  Pubmed ID: 22253293

A review of the available single nucleotide polymorphism (SNP) calling procedures for Illumina high-throughput sequencing (HTS) platform data reveals that most rely mainly on base-calling and mapping qualities as sources of error when calling SNPs. Thus, errors not involved in base-calling or alignment, such as those in genomic sample preparation, are not accounted for.

CarF Mediates Signaling by Singlet Oxygen, Generated Via Photoexcited Protoporphyrin IX, in Myxococcus Xanthus Light-induced Carotenogenesis

Journal of Bacteriology. Mar, 2012  |  Pubmed ID: 22267513

Blue light triggers carotenogenesis in the nonphototrophic bacterium Myxococcus xanthus by inducing inactivation of an anti-σ factor, CarR, and the consequent liberation of the cognate extracytoplasmic function (ECF) σ factor, CarQ. CarF, the protein implicated earliest in the response to light, does not resemble any known photoreceptor. It interacts physically with CarR and is required for its light-driven inactivation, but the mechanism is unknown. Blue-light sensing in M. xanthus has been attributed to the heme precursor protoporphyrin IX (PPIX), which can generate the highly reactive singlet oxygen species ((1)O(2)) by energy transfer to oxygen. However, (1)O(2) involvement in M. xanthus light-induced carotenogenesis remains to be established. Here, we present genetic evidence of the involvement of PPIX as well as (1)O(2) in light-induced carotenogenesis in M. xanthus and of how these are linked to CarF in the signal transduction pathway. Response to light was examined in carF-bearing and carF-deficient M. xanthus strains lacking endogenous PPIX due to deletion of hemB or accumulating PPIX due to deletion of hemH (hemB and hemH are early- and late-acting heme biosynthesis genes, respectively). This demonstrated that light induction of the CarQ-dependent promoter, P(QRS), correlated directly with cellular PPIX levels. Furthermore, we show that P(QRS) activation is triggered by (1)O(2) and is inhibited by exogenously supplied hemin and that CarF is essential for the action of (1)O(2). Thus, our findings indicate that blue light interaction with PPIX generates (1)O(2), which must be transmitted via CarF to trigger the transcriptional response underlying light-induced carotenogenesis in M. xanthus.

Abdominal Pathology in Patients With Diabetes Ketoacidosis

The American Journal of the Medical Sciences. Jan, 2012  |  Pubmed ID: 22270401

INTRODUCTION: The objective is to describe the incidence and nature of significant abdominal pathologies in patients with diabetes ketoacidosis (DKA) and abdominal pain. METHODS: Retrospective chart review (N = 86) of patients with DKA from January 1, 2005, to January 31, 2010, was performed. Data included demographics, comorbidities, compliance, chief complaints and physical findings, blood count, metabolic profile, lactic acid, glycosylated hemoglobin (HbA1C), amylase, lipase, anion gap, arterial gases, imaging and final diagnosis. Continuous variables were described as mean ± standard deviation and compared with the Student's t test. Categorical variables were expressed as percentages (%) and compared with the Mantel-Haenszel χ test. Univariate analysis was conducted among patients with and without significant abdominal pain and also with and without significant abdominal pathology. Two lipase strata were created at 400 U. Multivariate model to identify limits (confidence interval) of the estimated risk imposed by the predictor found significant in univariate analysis. A P value of ≤0.05 was considered significant. Stat View 5.0 (SAS Institute, Cary, NC) was used for the statistical analysis. RESULTS: In patients with abdominal pain, 17% had significant abdominal pathology mainly acute pancreatitis (AP). Serum amylase and lipase level were found to be an indicator of significant underlying pathology (both P values ≤0.001). The logistic model created showed that patients with lipase level ≥400 U have a 7% increased risk of having AP with confidence interval of 0.01 to 0.6. CONCLUSIONS: Patients with DKA and abdominal pain with lipase >400 U have an increased risk of significant underlying abdominal pathology (AP).

Treatment Given Near the End of Life in Castration-Resistant Prostate Cancer

The American Journal of Hospice & Palliative Care. Jan, 2012  |  Pubmed ID: 22218915

Chemotherapy treatment options are limited for patients with castration-resistant prostate cancer (CRPC). The purpose of this study is to report treatment use and adverse effects (AEs) within the last three months of life in patients with CRPC. Of the 88 patients identified, 32% received treatment within 3 months of death, and documented AEs occurred in 25% of patients. Of those, neutropenia (18.3%), nausea/vomiting (18.3%), and febrile neutropenia (13.6%) were the most frequent. Results of this study show high treatment utility towards the end-of-life in patients with CRPC, with one fourth of patients experiencing AEs. Attention to health-related quality of life becomes increasingly important as new treatments appear to have small impact on survival, and AEs of those treatments may significantly impact patient quality of life.

The Effects of Ethanol Upon Hydric Balance and Arterial Pressure in Rats: Folic Acid As a Possible Hypotensor

Life Sciences. Feb, 2012  |  Pubmed ID: 22227471

Chronic alcohol intake is related to hypertension. There are, however, few studies concerning the effect of ethanol upon hydric balance in relation to arterial pressure. Folic acid intake has beneficial effects upon the cardiovascular system decreasing hyperhomocysteinemia, however, more studies imply that it is related with other mechanisms. Therefore, we have studied the effects of chronic alcohol intake (30% v/v) upon hydric-saline balance and hypertension and have found that dietary supplementation with folic acid (8 mg/kg) improves the above parameters.

Gait Training in Human Spinal Cord Injury Using Electromechanical Systems: Effect of Device Type and Patient Characteristics

Archives of Physical Medicine and Rehabilitation. Mar, 2012  |  Pubmed ID: 22209475

To report the clinical improvements in spinal cord injury (SCI) patients associated with intensive gait training using electromechanical systems according to patient characteristics.

Quality Evaluation of Microscopy and Scanned Histological Images for Diagnostic Purposes

Micron (Oxford, England : 1993). Feb, 2012  |  Pubmed ID: 22099388

In this work we present a study for assessing and comparing the fidelity of biopsy and cytology images captured with two different devices, that is optical microscopes and scanners, at 40× magnification in bright field. The devices use different ways to magnify images. Microscopes use a set of lenses while scanners capture light through arrays of micro-photoreceptors. The objective is to carry out a quantitative evaluation to discern which of the two devices provides better image quality in terms of contrast, colour and stain. Since there is no unanimous consensus on quality metrics, we will make use of both an objective metric based on perceptual features, together with a subjective psychophysical test as the International Telecommunications Union (ITU) recommends in ITU-R BT.500 for such type of tests. Both techniques indicate a slight preference for the scanner over the microscope in terms of better image quality, considering defocus as the main problem followed by colour distortions. However, the image quality of both devices is suitable for clinical, educational and research purposes.