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Find video protocols related to scientific articles indexed in Pubmed.
Clicked bis-PEG-peptide conjugates for studying calmodulin-Kv7.2 channel binding.
Org. Biomol. Chem.
PUBLISHED: 09-30-2014
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The recombinant Kv7.2 calmodulin (CaM) binding site (Q2AB CaMBD) shows a high tendency to aggregate, thus complicating biochemical and structural studies. To facilitate these studies we have conceived bis-PEG-peptide CaMBD-mimetics linking helices A and B in single, easy to handle molecules. Short PEG chains were selected as spacers between the two peptide molecules, and a Cu(i)-catalyzed cycloaddition (CuAAC) protocol was used to assemble the final bis-PEG-peptide conjugate, by the convenient functionalization of PEG arms with azide and alkyne groups. The resulting conjugates, with a certain helical character in TFE solutions (CD), showed nanomolar affinity in a fluorescence CaM binding in vitro assay, higher than just the sum of the precursor PEG-peptide affinities, thus validating our design. The approach to these first described examples of Kv7.2 CaMBD-mimetics could pave the way to chimeric conjugates merging helices A and B from different Kv7 subunits.
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Primary clear cell carcinoma of the lung with salivary gland type features.
Bol Asoc Med P R
PUBLISHED: 07-29-2014
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Clear cell carcinoma of the lung is very rare, with few cases reported in the medical literature. Review of case studies show that these tumors have significant variation in clinical outcome, including metastatic disease. We present a very unusual case of primary clear cell lung carcinoma of salivary gland type.
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Chalcones as positive allosteric modulators of ?7 nicotinic acetylcholine receptors: a new target for a privileged structure.
Eur J Med Chem
PUBLISHED: 07-22-2014
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The ?7 acetylcholine nicotine receptor is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain and inflammation among other diseases. Therefore, the development of new agents that target this receptor has great significance. Positive allosteric modulators might be advantageous, since they facilitate receptor responses without directly interacting with the agonist binding site. Here we report the search for and further design of new positive allosteric modulators having the relatively simple chalcone structure. From the natural product isoliquiritigenin as starting point, chalcones substituted with hydroxyl groups at defined locations were identified as optimal and specific promoters of ?7 nicotinic function. The most potent compound (2,4,2',5'-tetrahydroxychalcone, 111) was further characterized showing its potential as neuroprotective, analgesic and cognitive enhancer, opening the way for future developments around the chalcone structure.
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Molecular and serological study of rickettsial infection in humans, and in wild and farm animals, in the province of Burgos, Spain.
Vector Borne Zoonotic Dis.
PUBLISHED: 05-27-2014
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Limited information is available on the presence of rickettsial infection in humans and animal reservoirs in Spain. Exposure to spotted fever group rickettsia in healthy humans and in farm and wild animals in the Province of Burgos, Spain, was examined by serological methods. Rickettsial DNA was also sought by PCR in animal samples. Of 102 human serum samples examined by indirect immunofluorescence assays (IFA), 5.88% were positive for antibodies against Rickettsia conorii (titers 1/128-1/512). Significant differences were detected in human seroprevalence with respect to age. In further IFAs, 102 out of 375 (27.2%) serum samples from the wild animals reacted with R. conorii antigens (titers 1/64-1/1024); 32 out of 281 (11.38%) samples from farm animals were also positive for R. conorii (titers 1/64-1/2048). The prevalence detected among total wild animals was significantly higher than among total farm animals. No rickettsial DNA was found by PCR in any farm or wild animal sample.
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Lipid Production by Pure and Mixed Cultures of Chlorella pyrenoidosa and Rhodotorula mucilaginosa Isolated in Nuevo Leon, Mexico.
Appl. Biochem. Biotechnol.
PUBLISHED: 05-06-2014
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Given the well-known environmental drawbacks of using fossil fuels, advances in the field of alternative energy have become a worldwide technological priority. Special interest has been focused on the production of biodiesel obtained from oleaginous microorganisms. In the present research, lipid production by two species, microalgae Chlorella pyrenoidosa and yeast Rhodotorula mucilaginosa was assessed, independently and in mixed culture to evaluate a possible synergy. Fatty acid analysis was performed by gas chromatography. Among pure and mixed cultures of both strains and several culturing conditions, the highest biomass and lipid productivity was obtained by C. pyrenoidosa (8.05 and 1.62 g/L, respectively). The results of this study showed that both strains used are in fact oleaginous strains as they were found to reach up to 20 % of lipids, in addition, lipids in both pure and mixed cultures were mainly of triglycerides (>90 %), composed of fatty acid chains between 16 and 18 carbons.
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De novo designed library of linear helical peptides: an exploratory tool in the discovery of protein-protein interaction modulators.
ACS Comb Sci
PUBLISHED: 04-22-2014
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Protein-protein interactions (PPIs) have emerged as important targets for pharmaceutical intervention because of their essential role in numerous physiological and pathological processes, but screening efforts using small-molecules have led to very low hit rates. Linear peptides could represent a quick and effective approach to discover initial PPI hits, particularly if they have inherent ability to adopt specific peptide secondary structures. Here, we address this hypothesis through a linear helical peptide library, composed of four sublibraries, which was designed by theoretical predictions of helicity (Agadir software). The 13-mer peptides of this collection fixes either a combination of three aromatic or two aromatic and one aliphatic residues on one face of the helix (Ac-SSEEX(5)ARNX(9)AAX(12)N-NH2), since these are structural features quite common at PPIs interfaces. The 81 designed peptides were conveniently synthesized by parallel solid-phase methodologies, and the tendency of some representative library components to adopt the intended secondary structure was corroborated through CD and NMR experiments. As proof of concept in the search for PPI modulators, the usefulness of this library was verified on the widely studied p53-MDM2 interaction and on the communication between VEGF and its receptor Flt-1, two PPIs for which a hydrophobic ?-helix is essential for the interaction. We have demonstrated here that, in both cases, selected peptides from the library, containing the right hydrophobic sequence of the hot-spot in one of the protein partners, are able to interact with the complementary protein. Moreover, we have discover some new, quite potent inhibitors of the VEGF-Flt-1 interaction, just by replacing one of the aromatic residues of the initial F(5)Y(9)Y(12) peptide by W, in agreement with previous results on related antiangiogenic peptides. Finally, the HTS evaluation of the full collection on thermoTRPs has led to a few antagonists of TRPV1 and TRPA1 channels, which open new avenues on the way to innovative modulators of these channels.
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Controlling magnetic Feshbach resonances in polar open-shell molecules with nonresonant light.
Phys. Rev. Lett.
PUBLISHED: 03-20-2014
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Magnetically tunable Feshbach resonances for polar paramagnetic ground-state diatomics are too narrow to allow for magnetoassociation starting from trapped, ultracold atoms. We show that nonresonant light can be used to engineer the Feshbach resonances in their position and width. For nonresonant field intensities of the order of 10(9) W/cm(2), we find the width to be increased by 3 orders of magnitude, reaching a few Gauss. This opens the way for producing ultracold molecules with sizable electric and magnetic dipole moments and thus for many-body quantum simulations with such particles.
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Enantioselective synthesis of PPAR (peroxisome proliferator-activated receptors) agonists and antagonists.
Curr Top Med Chem
PUBLISHED: 02-21-2014
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This review deals with stereoselective issues in PPAR ligands some of which are in clinical use for treating certain metabolic disorders. After a short introduction of these nuclear receptor and their agonists, some cases of enantioselective separations are reported. The main part concerns stereoselective synthesis first starting with asymmetric synthesis from chiral precursors followed by what we refer to as "true" enantioselective methods. Some examples are discussed in detail for each particular heading.
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Detection of ischemic penumbra using combined perfusion and T2* oxygen challenge imaging.
Int J Stroke
PUBLISHED: 01-29-2014
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Acute ischemic stroke is common and disabling, but there remains a paucity of acute treatment options and available treatment (thrombolysis) is underutilized. Advanced brain imaging, designed to identify viable hypoperfused tissue (penumbra), could target treatment to a wider population. Existing magnetic resonance imaging and computed tomography-based technologies are not widely used pending validation in ongoing clinical trials. T2* oxygen challenge magnetic resonance imaging, by providing a more direct readout of tissue viability, has the potential to identify more patients likely to benefit from thrombolysis - irrespective of time from stroke onset - and patients within and beyond the 4·5?h thrombolysis treatment window who are unlikely to benefit and are at an increased risk of hemorrhage.
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Selective sensitization to Penicillin V with tolerance to other betalactams.
Recent Pat Inflamm Allergy Drug Discov
PUBLISHED: 01-09-2014
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Penicillin G and V have the same betalactam ring. Penicillin V (phenoxymethylpenicillin) results from the substitution of the phenyl acetic acid of benzylpenicillin by the phenoxy methyl side chain.
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Mixed-field orientation of molecules without rotational symmetry.
J Chem Phys
PUBLISHED: 12-24-2013
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The mixed-field orientation of an asymmetric-rotor molecule with its permanent dipole moment nonparallel to the principal axes of polarizability is investigated experimentally and theoretically. We find that for the typical case of a strong, nonresonant laser field and a weak static electric field complete 3D orientation is induced if the laser field is elliptically polarized and if its major and minor polarization axes are not parallel to the static field. For a linearly polarized laser field solely the dipole moment component along the most polarizable axis of the molecule is relevant resulting in 1D orientation even when the laser polarization and the static field are nonparallel. Simulations show that the dipole moment component perpendicular to the most-polarizable axis becomes relevant in a strong dc electric field combined with the laser field. This offers an alternative approach to 3D orientation by combining a linearly polarized laser field and a strong dc electric field arranged at an angle equal to the angle between the most polarizable axis of the molecule and its permanent dipole moment.
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[The measurement of patient safety culture: a literature review].
Rev Enferm
PUBLISHED: 11-20-2013
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To determine if patient safety culture is measurable in healthcare organizations, if it has done, and in this case, how it is measured and which aspects have been taken into account.
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Pathogenesis, diagnosis and treatment of non-alcoholic fatty liver disease.
Rev Esp Enferm Dig
PUBLISHED: 11-12-2013
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Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of alterations that go from simple steatosis to steatohepatitis and cirrhosis. Type 2 diabetes mellitus (DM-2) and obesity are the principle factors associated to NAFLD. A 20-30 % prevalence in general population has been described. The survival of this type of patient is lower than the general population´s, showing a higher incidence of hepatic and cardiovascular complications. The aetiopathogenesis is still unclear, but we know the intervention of different factors that produce fatty-acid accumulation in hepatic parenchyma, causing oxidative stress, oxygen-free radicals and the synthesis of an inflammatory cascade, that determine the progression of this disease from steatosis up to advanced fibrosis.The diagnostic gold-standard is still the liver biopsy, even though the development of newer non-invasive techniques, like serological and imaging (radiology), have opened a new field for research that allows bloodless testing of these patients and better study of the natural history of this disease. Nowadays, there is still no specific treatment for NAFLD. The development of healthy life habits and moderate exercise continue to be the pillars of treatment. Different pharmacological approaches have been studied and applied, such as the control of insulin resistance, lowering cholesterol levels, antioxidants, and other alternatives in experimental trials.
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Paracetamol-induced fixed drug eruption at an unusual site.
Recent Pat Inflamm Allergy Drug Discov
PUBLISHED: 07-22-2013
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Paracetamol (acetaminophen) is a widely used analgesic/antipyretic drug for which hypersensitivity reactions appear to be increasingly frequent. Objective: We report the case of a woman who experienced several delayed selective reactions induced by paracetamol: fixed drug eruptions (FDEs) with typical features but an unusual distribution (hard palate and a maculopapular rash.
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Target of rapamycin (TOR) kinase in Trypanosoma brucei: an extended family.
Biochem. Soc. Trans.
PUBLISHED: 07-19-2013
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The complex life cycle of Trypanosoma brucei provides an excellent model system to understand signalling pathways that regulate development. We described previously the classical functions of TOR (target of rapamycin) 1 and TOR2 in T. brucei. In a more recent study, we described a novel TOR kinase, named TOR4, which regulates differentiation from the proliferative infective form to the quiescent form. In contrast with TOR1 loss-of-function, down-regulation of TOR4 triggers an irreversible differentiation process through the development of the insect pre-adapted quiescent form. TOR4 governs a signalling pathway distinct from those controlled by the conventional TOR complexes TORC1 and TORC2. Depletion of TOR4 induces all well-known characteristics of the quiescent developmental stage in trypanosomes, including expression of the PAD (proteins associated with differentiation) surface proteins and transcriptional down-regulation of the VSG (variant surface glycoprotein) gene. TOR4 kinase forms a structurally and functionally distinct complex named TORC4. TOR4 associates with LST8 (lethal with sec-13 protein 8) and other factors including an armadillo-domain-containing protein and the major vault protein, which probably serves as a scaffold for this kinase. Research in T. brucei, a protozoan parasite that diverged from the eukaryotic tree early in evolution, may help to uncover new functions of TOR kinases.
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Efficacy and safety of ERCP in a low-volume hospital.
Rev Esp Enferm Dig
PUBLISHED: 05-11-2013
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Background and aims: there is little scientific evidence on the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) performed in low-volume hospitals; however, in our country, it is growing up its implementation. The objectives of our study were to evaluate the efficacy and safety of this technique performed by two endoscopists with basic training in a center of this nature and analyze the learning curve in the first procedures.Patients and methods: single-center retrospective study of the first 200 ERCP performed in our hospital (analyzing the evolution between the first 100 and 100 following procedures), comparing them with the quality standards proposed in the literature.Results: from February 2009 to April 2011, we performed 200 ERCP in 169 patients, and the most common indications were: Choledocholithiasis (77 %), tumors (14.5 %) and other conditions (8.5 %). The cannulation rate rose from 85 % in the first 100 ERCPto 89 % in the next 100 procedures, clinical success from 81 % to 87 %, decreasing the post-ERCP acute pancreatitis rate from 11 % to 4 %, upper gastrointestinal bleeding (UGIB) from 3 % to 2 % and acute cholangitis from 4 % to 1 %. There was a death from a massive UGIB in a cirrhotic patient in the first group of patients and a case of biliary perforation resolved by surgery in the second one.Conclusions: the results obtained after performing 200 procedures support the ability to practice ERCP in low-volume hospitals obtaining levels of efficacy and safety in accordance with published quality standards.
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The Parkinsons disease-associated GPR37 receptor-mediated cytotoxicity is controlled by its intracellular cysteine-rich domain.
J. Neurochem.
PUBLISHED: 02-06-2013
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GPR37, also known as parkin-associated endothelin-like receptor (Pael-R), is an orphan G protein-coupled receptor (GPCR) that aggregates intracellularly in a juvenile form of Parkinsons disease. However, little is known about the structure or function of this receptor. Here, in order to better understand the functioning of this receptor, we focused on the GPR37 C-terminal tail, in particular on a cystein-enriched region. Thus, we aimed to reveal the role of these residues on receptor plasma membrane expression and function, and also whether the presence of this cysteine-rich domain is linked to the previously described receptor-mediated cytotoxicity. Interestingly, while the deletion of six cysteine residues within this region did not affect receptor internalization it promoted GPR37 plasma membrane expression and signaling. Furthermore, the removal of the C-terminal cysteine-rich domain protected against GPR37-mediated apoptosis and cell death. Overall, we identified a GPR37 domain, namely the C-terminal tail cysteine-rich domain, which played a critical role in receptor cell surface expression, function and GPR37-mediated cytotoxicity. These results might contribute to better comprehend the pathophysiology (i.e. in Parkinsons disease) of this rather unknown member of the GPCR family.
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Helical peptides from VEGF and Vammin hotspots for modulating the VEGF-VEGFR interaction.
Org. Biomol. Chem.
PUBLISHED: 02-04-2013
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The design, synthesis, conformational studies and binding affinity for VEGF receptors of a collection of linear and cyclic peptide analogues of the N-terminal ?-helix fragments 13-25 of VEGF and 1-13 of Vammin are described. Linear 13(14)-mer peptides were designed with the help of an AGADIR algorithm and prepared following peptide solid-phase synthetic protocols. Cyclic peptide derivatives were prepared on-resin from linear precursors with conveniently located Glu and Lys residues, by the formation of amide linkages. Conformational analysis, CD and NMR, showed that most synthesized peptides have a clear tendency to be structured as ?-helices in solution. Some of the peptides were able to bind a VEGFR-1 receptor with moderate affinity. In addition to the described key residues (Phe17, Tyr21 and Tyr25), Val14 and Val20 seem to be relevant for affinity.
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Highly functionalized 1,2-diamino compounds through reductive amination of amino acid-derived ?-keto esters.
PLoS ONE
PUBLISHED: 01-07-2013
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1,2-Diamine derivatives are valuable building blocks to heterocyclic compounds and important precursors of biologically relevant compounds. In this respect, amino acid-derived ?-keto esters are a suitable starting point for the synthesis of ?,?-diamino ester derivatives through a two-step reductive amination procedure with either simple amines or ?-amino esters. AcOH and NaBH(3)CN are the additive and reducing agents of choice. The stereoselectivity of the reaction is still an issue, due to the slow imine-enamine equilibria through which the reaction occurs, affording mixtures of diastereoisomers that can be chromatographically separated. Transformation of the ?,?-diamino esters into pyrrolidinone derivatives allows the configuration assignment of the linear compounds, and constitutes an example of their potential application in the generation of molecular diversity.
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Diamine and aminoalcohol derivatives active against Trypanosoma brucei.
Bioorg. Med. Chem. Lett.
PUBLISHED: 09-22-2011
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Twenty compounds selected as representative members of three series of long-chain 1,2-diamines, 2-amino-1-alkanols and 1-amino-2-alkanols structurally related to dihydrosphingosin, were synthesized and tested in vitro for their ability to inhibit the sleeping sickness parasites Trypanosoma bruceirhodesiense and Trypanosoma brucei gambiense. Eight compounds showed EC(50) values in the submicromolar range, with selectivity indexes up to 39 related to the respective cytotoxicity values for Vero cells. The parasite phenotype detected after treatment with the most potent compounds showed irreversible cell morphology alterations of the flagellar pocket that lead to inhibition of cell growth and parasite death.
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Cyclic amino acid linkers stabilizing key loops of brain derived neurotrophic factor.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-12-2011
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Based on ?-turn-like BDNF loops 2 and 4, involved in receptor interaction, cyclic peptide replicas were designed, synthesized and tested. In addition to the native turn residues, the cyclic peptides include a linker unit between the N- and C-termini, selected by molecular modeling among various non-proteinogenic cyclic amino acids. NMR conformational studies showed that most of the cyclic peptides were able to adopt turn-like structures. Several of the analogues displayed significant inhibition of the BDNF-induced TrkB receptor phosphorylation, and hence could be useful templates for developing improved antagonists for this receptor.
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Disulfide and amide-bridged cyclic peptide analogues of the VEGF????? fragment: synthesis, conformational analysis and biological evaluation.
Bioorg. Med. Chem.
PUBLISHED: 07-26-2011
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The design, synthesis, conformational studies and binding affinity for VEGFR-1 receptors of a collection of linear and cyclic peptide analogues of the ?-hairpin fragment VEGF(81-91) are described. Cyclic 11-mer peptide derivatives were prepared from linear precursors with conveniently located Cys, Asp or Dap residues, by the formation of disulfide and amide bridges, using solid-phase synthesis. Molecular modelling studies indicated a tendency to be structured around the central ?-turn of the VEGF(81-91) ?-hairpin in most synthesized cyclic compounds. This structural behavior was confirmed by NMR conformational analysis. The NHCO cyclic derivative 7 showed significant affinity for VEGFR-1, slightly higher than the native linear fragment, thus supporting the design of mimics of this fragment as a valid approach to disrupt the VEGF/VEGFR-1 interaction.
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Larger helical populations in peptides derived from the dimerization helix of the capsid protein of HIV-1 results in peptide binding toward regions other than the "hotspot" interface.
Biomacromolecules
PUBLISHED: 07-26-2011
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The C-terminal domain (CTD) of the capsid protein (CA) of HIV-1 participates both in the formation of CA hexamers and in the joining of hexamers through homodimerization to form the viral capsid. Intact CA and the CTD are able to homodimerize with similar affinity (~15 ?M); CTD homodimerization involves mainly an ?-helical region. We have designed peptides derived from that helix with predicted higher helical propensities than the wild-type sequence while keeping residues important for dimerization. These peptides showed a higher helicity than that of the wild-type peptide, although not as high as theoretically predicted, and proved to be able to self-associate with apparent affinities similar to that of the whole CTD. However, binding to CTD mainly occurs at the last helical region of the protein. Accordingly, most of those peptides are unable to inhibit CA polymerization in vitro. Therefore, there is a subtle tuning between monomer-monomer interactions important for CTD dimerization and the maximal helical content achieved by the wild-type sequence of the interface.
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Quaternary ?,?-2-oxoazepane ?-amino acids: synthesis from ornithine-derived ?-lactams and incorporation into model dipeptides.
J. Org. Chem.
PUBLISHED: 07-18-2011
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To explore further the chemistry of amino acid-derived ?-lactams, their conversion to ?,?-heterocyclic quaternary amino acid derivatives is investigated. The latter derivatives, containing 2-oxoazepane as the ?,?-substituent, are synthesized by a simple Pd-C-catalyzed hydrogenolysis of Orn(Z)-derived 2-azetidinones. The rearrangement from four- to seven-membered lactam ring is driven by the key intramolecular opening of the 1-Boc-?-lactam, initiated by 7-exotrig ring closure from the NH(2) of the Orn side chain. The synthetic route is applied to the stereoselective preparation of enantiomerically pure 4-amino-3-methyl-2-oxoazepane-4-carboxylate derivatives, for which the structure and configuration is confirmed by X-ray diffraction. Molecular modeling and NMR experiments indicate that these quaternary amino acids are able to drive the adoption of ?-turn secondary structures when incorporated in model dipeptide derivatives.
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Solid-phase synthesis of a library of amphipatic hydantoins. Discovery of new hits for TRPV1 blockade.
ACS Comb Sci
PUBLISHED: 07-08-2011
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Some heterocyclic systems, called privileged scaffolds, appear frequently in bioactive products and marketed drugs. The combination of a recognized privileged scaffold (hydantoin) and a functional group with high incidence in bioactive molecules (guanidine) guided the design of a library of amphipatic compounds, which allowed the discovery of novel TRPV1 ion channel blockers. The library was synthesized by parallel solid-phase synthesis from an orthogonally protected resin-bound Lys-Lys skeleton. Key steps of the synthetic procedure were the construction of the hydantoin ring, by reaction of the N-terminal amino group with N,N-disuccinimidyl carbonate (DSC) and subsequent base-induced cyclization, and the guanidinylation of the C-terminal Lys side-chain after removal of the Alloc protecting-group. The preliminary biological studies have allowed the identification of some of the key structural features directing the blockage of capsaicin-induced Ca(2+) influx through TRPV1 channels, particularly, the strong preference showed for highly lipophilic acyl groups and substituted guanidine moieties. Active compounds based on this new pharmacophoric scaffold that display in vitro and in vivo inhibitory activity.
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Trp-Trp pairs as ?-hairpin stabilisers: hydrogen-bonded versus non-hydrogen-bonded sites.
Org. Biomol. Chem.
PUBLISHED: 06-14-2011
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Trp-Trp pairs have emerged as a successful strategy for ?-hairpin stabilization. Using loop 3 of Vammin as a template, we experimentally demonstrate that the contribution of Trp-Trp pairs to ?-hairpin stability depends on ?-sheet periodicity, that is, they are stabilising at non-hydrogen-bonded sites, but not at hydrogen-bonded positions.
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Effects of adrenocorticotropic hormone challenge and age on hair cortisol concentrations in dairy cattle.
Can. J. Vet. Res.
PUBLISHED: 06-09-2011
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Dairy cattle suffer stress from management and production; contemporary farming tries to improve animal welfare and reduce stress. Therefore, the assessment of long-term hypothalamic-pituitary-adrenal function using non-invasive techniques is useful. The aims in this study were: to measure cortisol concentration in cow and calves hair by radioimmunoassay (RIA), to test cortisol accumulation in bovine hair after adrenocorticotropic hormone (ACTH) challenges, and determine the influence of hair color on cortisol concentrations. Fifteen Holstein heifers were allotted to 3 groups (n = 5 each): in control group (C), just the hair was sampled; in the saline solution group (SS), IV saline solution was administered on days 0, 7, and 14; and the ACTH group was challenged 3 times with ACTH (0.15 UI per kg of body weight) on days 0, 7, and 14. Serum samples from the SS and ACTH groups were obtained 0, 60 and 90 min post-injection. Serum cortisol concentration was greater 60 and 90 min after injection with ACTH. Hair was clipped on days 0, 14, 28, and 44. Hair cortisol was methanol extracted and measured by RIA. Hair cortisol was preserved for 11 mo. Hair cortisol concentrations in the ACTH group were greater than in the saline and control groups on days 14 and 28, but not on day 44. Concentrations were greater in calves than in cows and greater in white hair than in black hair. Cortisol accumulated in bovine hair after ACTH challenges, but the concentration was affected by both age and hair color. If hair color effects are taken into account, assessing cortisol concentration in hair is a potentially useful non-invasive method for assessing stress in cattle.
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Optically active 1,3,4,4-tetrasubstituted ?-lactams: synthesis and evaluation as tumor cell growth inhibitors.
Eur J Med Chem
PUBLISHED: 06-09-2011
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The in vitro cytotoxicity assays of several enantiopure (3S,4S)- and (3R,4R)-1,3,4,4-tetrasubstituted ?-lactams derived from amino acids have shown that the (3S,4S)-4-benzyl-1-p-methoxybenzyl-3-methyl-4-methoxycarbonyl derivative 2a, obtained from Phe, displays significant activity, which is comparable to that of the anticancer drug Doxorubicin against HT29 cell lines. Modifications at positions 1 and 4 of the ?-lactam ring led to identify the Tyr(2,6-ClBz) analogu 26d with similar activity data to those of 2a. The synthesis and SAR of all these tetrasubstituted ?-lactams are reported here.
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Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. Validation using [14C]2-deoxyglucose autoradiography.
J. Cereb. Blood Flow Metab.
PUBLISHED: 05-11-2011
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Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T(2)(*) MRI (T(2)(*) OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T(2)(*) signal change during OC. [(14)C]2-deoxyglucose (2-DG) autoradiography was combined with T(2)(*) OC to determine metabolic status of T(2)(*)-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147 ± 32 minutes after stroke, T(2)(*) signal change was measured during a 5-minute 100% OC, immediately followed by 125 ?Ci/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T(2)(*)-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T(2)(*) signal increase of 9.22% ± 3.9% (mean ± s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T(2)(*) signal change was negligible in ischemic core, 3.2% ± 0.78% in contralateral regions, and 1.41% ± 0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.
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Stroke penumbra defined by an MRI-based oxygen challenge technique: 2. Validation based on the consequences of reperfusion.
J. Cereb. Blood Flow Metab.
PUBLISHED: 05-11-2011
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Magnetic resonance imaging (MRI) with oxygen challenge (T(2)(*) OC) uses oxygen as a metabolic biotracer to define penumbral tissue based on CMRO(2) and oxygen extraction fraction. Penumbra displays a greater T(2)(*) signal change during OC than surrounding tissue. Since timely restoration of cerebral blood flow (CBF) should salvage penumbra, T(2)(*) OC was tested by examining the consequences of reperfusion on T(2)(*) OC-defined penumbra. Transient ischemia (109 ± 20 minutes) was induced in male Sprague-Dawley rats (n=8). Penumbra was identified on T(2)(*)-weighted MRI during OC. Ischemia and ischemic injury were identified on CBF and apparent diffusion coefficient maps, respectively. Reperfusion was induced and scans repeated. T(2) for final infarct and T(2)(*) OC were run on day 7. T(2)(*) signal increase to OC was 3.4% in contralateral cortex and caudate nucleus and was unaffected by reperfusion. In OC-defined penumbra, T(2)(*) signal increased by 8.4% ± 4.1% during ischemia and returned to 3.25% ± 0.8% following reperfusion. Ischemic core T(2)(*) signal increase was 0.39% ± 0.47% during ischemia and 0.84% ± 1.8% on reperfusion. Penumbral CBF increased from 41.94 ± 13 to 116.5 ± 25 mL per 100 g per minute on reperfusion. On day 7, OC-defined penumbra gave a normal OC response and was located outside the infarct. T(2)(*) OC-defined penumbra recovered when CBF was restored, providing further validation of the utility of T(2)(*) OC for acute stroke management.
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[Promoting routine human immunodeficiency virus testing in primary care].
Gac Sanit
PUBLISHED: 03-31-2011
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To promote human immunodeficiency virus (HIV) testing in the primary care setting and to describe patients attitudes toward this practice.
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The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing.
PLoS Negl Trop Dis
PUBLISHED: 03-26-2011
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Target repurposing utilizes knowledge of "druggable" targets obtained in one organism and exploits this information to pursue new potential drug targets in other organisms. Here we describe such studies to evaluate whether inhibitors targeting the kinase domain of the mammalian Target of Rapamycin (mTOR) and human phosphoinositide-3-kinases (PI3Ks) show promise against the kinetoplastid parasites Trypanosoma brucei, T. cruzi, Leishmania major, and L. donovani. The genomes of trypanosomatids encode at least 12 proteins belonging to the PI3K protein superfamily, some of which are unique to parasites. Moreover, the shared PI3Ks differ greatly in sequence from those of the human host, thereby providing opportunities for selective inhibition.
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TRPV1 modulators: structure-activity relationships using a rational combinatorial approach.
Bioorg. Med. Chem. Lett.
PUBLISHED: 02-20-2011
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A discrete library of linear and hydantoin-containing dipeptide derivatives, based on the Lys-Trp(Nps) scaffold, was prepared by solid-phase synthesis. SAR studies indicated that potency for TRPV1 blockade and selectivity towards NMDA is mainly dictated by the side-chain length and the basic nature of ?, ?-groups in the N-terminal residue. The 2-Nps moiety at position 2 of Trp indole ring is preferred over the 2-pyridine one.
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Parallel solid-phase synthesis of a small library of linear and hydrocarbon-bridged analogues of VEGF(81-91): potential biological tools for studying the VEGF/VEGFR-1 interaction.
Bioorg. Med. Chem.
PUBLISHED: 01-24-2011
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The design, synthesis and binding affinity for VEGFR-1 receptors of a small library of linear and cyclic analogues of the VEGF(81-91) fragment are described. Cyclic 11- and 10-mer peptide derivatives were prepared using parallel solid-phase protocols. The formation of hydrocarbon alkene-bridged cyclic peptides was achieved through optimized ring-closing metathesis reactions from linear derivatives with conveniently located allylGly residues. Alkane-bridged analogues were successfully obtained by ulterior on-resin hydrogenation. Binding assays showed that some of these compounds were able to compete with labeled VEGF for interaction with the VEGFR-1 receptor. Several peptide derivatives, 2, 7 and 8, showed modest but significant binding affinity, indicating that the designed peptide could mimic the VEGF(81-91) fragment and therefore disrupt the VEGF/VEGFR-1 interaction. This fact opens the way for using these peptides as the starting point for biological/pharmacological tools to deeply investigate this protein-protein system.
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Synthesis and SAR studies on azetidine-containing dipeptides as HCMV inhibitors.
Bioorg. Med. Chem.
PUBLISHED: 10-18-2010
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SAR studies on an azetidine-containing dipeptide prototype inhibitor of HCMV are described. Three series of structurally modified analogues, involving substitutions at the N- and C-terminus, and at the C-terminal side-chain were synthesized and evaluated for antiviral activity. Aliphatic or no substituents at the C-carboxamide group, an aliphatic C-terminal side-chain, as well as a benzyloxycarbonyl moiety at the N-terminus were absolute requirements for anti-HCMV activity. The conformational restriction induced by the 2-azetidine residue into the dipeptide derivatives, identified by (1)H NMR as a ?-type reverse turn, seems to have influence on the activity of these molecules.
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Exemestane and chemotherapy as first-line treatment of metastatic breast cancer: results of a phase II study.
Clin. Breast Cancer
PUBLISHED: 08-14-2010
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Metastatic breast cancer remains largely incurable. Strategies involving the combination of the selective estrogen receptor modulator tamoxifen and chemotherapy have been abandoned in view of unacceptable toxicity because of thromboembolic events. The aim of this study was to investigate the safety and efficacy of the third-generation steroidal aromatase inhibitor exemestane plus chemotherapy.
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Retinal-image quality and contrast-sensitivity function in age-related macular degeneration.
Curr. Eye Res.
PUBLISHED: 08-03-2010
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In this article, retinal-image quality and contrast sensitivity were measured in 25 patients with age-related macular degeneration (ARMD) and 15 patients with normal retinal health.
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Solid-phase synthesis of new Trp(Nps)-containing dipeptide derivatives as TRPV1 channel blockers.
Molecules
PUBLISHED: 06-11-2010
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Trp(Nps)-Lys-NH(2) derivatives, bearing alkyl or guanidine groups either at the N-terminus or on the Lys side-chain or at both positions were conveniently prepared on solid-phase and evaluated as TRPV1 channel antagonists.
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[Chronic C hepatitis genotype 4].
Med Clin (Barc)
PUBLISHED: 02-27-2010
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The hepatitis C virus (HCV) is one of the most important causal agents of liver disease. Genotype 4 is responsible for 20% of chronic hepatitis and in several countries of the Mediterranean area it has been reported that the prevalence is increasing. The HCV infection develops to chronicity in more than 90%, 20% may have cirrhosis and 5-10% develop hepatocellular carcinoma. There has been speculation about a possible association of genotype 4 with the development of hepatocellular carcinoma, but it seems related to other concomitant causes of liver disease. Treatment is based on the use of pegylated interferon ?-2a (180 mg/week) or pegylated-interferon ?-2b (1.5mg/kg/wk) plus ribavirin (1000-1200 mg/day) for one year. With this regimen, there have been reported sustained virological response (SVR) rates around 65%. There are differences in the SVR rates according to the degree of fibrosis, associated concurrent infections and the presence of specific serologic markers. Nitazoxanide has been used in combination with the classic combination therapy, achieving an improvement in the results.
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2-alkyl-2-carboxyazetidines as ?-turn inducers: incorporation into neurotrophin fragments.
Amino Acids
PUBLISHED: 01-18-2010
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Conveniently substituted 2-alkyl-2-carboxyazetidine amino acids have been incorporated into NGF and NT3 tetrapeptide sequences to investigate their utility as reverse turn inducers (?- vs. ?-turns). Despite the presence of an Asp residue at i position, highly preferred in ?-turns, molecular modeling and NMR studies indicated that the azetidine-containing peptides mainly stabilized ?-turn conformations.
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A role for ring-closing metathesis in medicinal chemistry: Mimicking secondary architectures in bioactive peptides.
Med Res Rev
PUBLISHED: 01-14-2010
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Synthetically versatile and easy to carry out, Ring-Closing Metathesis (RCM) constitutes an attractive chemical tool, easily amenable for multiple substrates in mild conditions. In medicinal chemistry, the use of RCM has been especially prolific during the last few years. An important application that has benefited from this reaction is the stabilization of spatial conformations in bioactive peptides, since their 3D arrangements play relevant roles in biomolecular recognition processes. RCM reaction is being widely used to introduce conformational constraints into small peptides, through the generation of cyclic structures from appropriate linear precursors. As an alternative to strategies like disulfide or lactam-bridged cyclizations, RCM shows the additional advantage of generating hydrocarbon bridges, less prone to metabolic degradation, and metabolically more stable, which could benefit their pharmacokinetic properties. Particularly remarkable is the application of RCM to the preparation of small peptide modulators able to mimic epitopes identified as hotspots within the surface contact areas in protein-protein interactions (PPIs). This review deals with the replacement of S-S and thioether linkages of cyclic peptides by C-C-bridges and with the stabilization of peptide secondary architectures (?-helix, ?-hairpins, ?-turns) through RCM, as a useful strategy for the modulation of therapeutically relevant signaling pathways. ??© 2010 Wiley Periodicals, Inc. Med Res Rev 31: 677-715, 2011.
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Further evidence for 2-alkyl-2-carboxyazetidines as gamma-turn inducers.
J. Org. Chem.
PUBLISHED: 10-03-2009
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Reverse turns, a common motif in proteins and peptides, have attracted attention due to their relevance in a wide variety of biological processes. In an attempt to artificially imitate and stabilize these turns in short peptides, we have developed versatile synthetic methodologies for the preparation of 2-alkyl-2-carboxyazetidines and incorporated them into the i + 1 position of model tetrapeptides, where they have shown a tendency to induce gamma-turns. However, to ascertain the general utility of these restricted amino acids as gamma-type reverse turn inducers, it was then required to study the conformational preferences when located at other positions. To this end, model tetrapeptides R-CO-Ala-Xaa-NHMe, containing differently substituted azetidine moieties (Xaa = Aze, 2-MeAze, 2-BnAze) at the i + 2 position, were synthesized and subjected to a thorough conformational analysis. The theoretical and experimental results obtained, including the X-ray diffraction structure of a dipeptide derivative containing this skeleton, provide evidence that the 2-alkyl-2-carboxyazetidine scaffold is able to efficiently induce gamma-turns when incorporated into these short peptides, irrespective of their localization in the peptide chain.
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Spectrum of anemia associated with chronic liver disease.
World J. Gastroenterol.
PUBLISHED: 09-30-2009
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Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically significant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirin-induced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by deficiency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.
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Multiple pilomatricomas in association with trisomy 9.
Pediatr Dermatol
PUBLISHED: 08-20-2009
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Multiple appearance of pilomatricoma is a rare phenomenon that has been associated with some diseases like Gardner syndrome, myotonic dystrophy, and Rubinstein-Taybi syndrome. We present a case of association of multiple pilomatricoma and trisomy 9, which represents the third published in literature. As a result of the small prevalence of these two entities, we believe they could be related.
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Epidemiological study of rickettsial infections in patients with hypertransaminemia in Madrid (Spain).
Int J Environ Res Public Health
PUBLISHED: 08-19-2009
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A retrospective analysis was performed to detect anti-rickettsial antibodies in the serum of patients with hypertransaminemia of unknown etiology, and in that of healthy members of the general population of Madrid (Spain). Among 143 patients 16 (11.2%) were positive for anti-R. conorii IgG antibodies and 7% for R. typhi. PCR analysis was performed in patients with IgM antibodies. Among 143 healthy subjects from the general population, seven (4.9%) were positive for anti-R. conorii IgG antibodies, and 2.8% for R. typhi. These results show that anti-rickettsial antibodies are more commonly detected in patients with hypertransaminemia than in healthy people.
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Novel findings on trypanosomatid chemotherapy using DNA topoisomerase inhibitors.
Mini Rev Med Chem
PUBLISHED: 06-13-2009
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Trypanosomatid (order Kinetoplastida)-borne neglected tropical diseases - African and American trypanosomiasis and leishmaniasis - are amongst the most devastating health threats of underdeveloped, developing and poor countries. Climatic changes due to global warming, tourism exchange and increasing migratory fluxes are re-distributing the endemic subtropical location of these diseases to a new scenario with a rising presence in developed countries during the last decades. In addition, the proved opportunistic transmission of these diseases through contaminated syringes shared by drug users, in combination with immunosuppression processes linked to HIV infections and the poor response to the typical treatments, point to AIDS patients as a sensitive sub-population prone to suffer from these diseases. DNA topoisomerases are the "molecular engineers" that unravel the DNA during replication and transcription. The mechanism of DNA unwinding includes the scission of a single DNA strand - type I topoisomerases - or both DNA strands - type II topoisomerases - establishing transient covalent bonds with the scissile end. Camptothecin and etoposide - two natural drugs whose semi-synthetic derivatives are currently used in cancer chemotherapy - target types I and II DNA-topoisomerases respectively, stabilizing ternary topoisomerase-DNA-drug covalent complexes, which irreversibly poison the enzymes. Several differences between parasite and host DNA topoisomerases have pointed to these enzymes as potential drug targets in Trypanosomatids. The unusual localization inside the mitochondria-like organellum - the kinetoplast - linked to mini and maxicircles, as well as the uncommon heterodimeric structure of the DNA topoisomerase IB subfamily, make these proteins unquestionable targets for drug intervention against trypanosomatids.
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Congenital hemangioma: a report of evolution from rapidly involuting to noninvoluting congenital hemangioma with aberrant Mongolian spots.
Pediatr Dermatol
PUBLISHED: 05-08-2009
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Congenital hemangiomas are unusual vascular tumors that are fully developed at the time of delivery. We report a case of an infant with an exophytic congenital hemangioma with features of a rapidly involuting hemangioma on the arm which over 3 years decreased in volume but continued to persist with features of a noninvoluting congenital hemangioma. He also had aberrant, persistent Mongolian spots on both legs. To our knowledge, this association has not been reported to date.
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Disulfide bonds versus TrpTrp pairs in irregular beta-hairpins: NMR structure of vammin loop 3-derived peptides as a case study.
Chembiochem
PUBLISHED: 03-19-2009
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Structural studies on model peptides have led to a good understanding of the rules behind the formation and stability of regular beta-hairpins. To test their applicability to the successful design of irregular beta-hairpins with long loops and/or beta-bulges at the strands, we mimicked loop 3 of vammin, a 4:6 beta-hairpin with a non-Gly beta-bulge. The most stabilising cross-strand pairs, disulfide bonds or/and TrpTrp pairs, were incorporated at non-hydrogen-bonded sites in peptides spanning the 69-80 region of vammin. According to NMR data, these modified peptides adopt beta-hairpin conformations as intended by design. The Trp-containing peptides reproduce even the unusual positive phi angle for the Gln residue, with the indole rings in the preferred edge-to-face orientation. For the first time the beta-hairpin-stabilising capacities of a disulfide bond and a TrpTrp pair are compared in the same model system. We found that the contribution to stability of the noncovalent indole-indole interaction is larger than that of the covalent disulfide bond, and that their combination gives rise to an even more stable beta-hairpin.
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Research on cognitive, social and cultural processes of written communication.
Cogn Process
PUBLISHED: 01-22-2009
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This article compiles the investigations carried out by a Research Group of the University of Granada, Spain. Its different projects on writings cognitive social and cultural processes have been supported by the Spanish Government. This line of research joined together linguistic, psychological, social and cultural contributions to the development of writing from the 1970s. Currently, this line of research develops in collaboration with other European Universities: (a) Interuniversity Centre for Research On Cognitive Processing in Natural and Artificial Systems (ECONA), "La Sapienza" University of Rome (Italy); (b) Anadolu University, (Eskisehir, Turkey); (c) Coimbra University (Portugal); (d) University of Zaragoza (Spain); (e) the Institute of Education of the University of London (United Kingdom). The aforementioned collaboration is materializing into projects like the International Master on Multilingual Writing: Cognitive, Intercultural and Technological Processes of Written Communication ( http://www.multilingualwriting.com ) and the International Congress: Writing in the twenty-first Century: Cognition, Multilinguisim and Technologies, held in Granada ( http://www.asprogrades.org ). This research line is focussed on the development of strategies in writing development, basic to train twenty-first century societies citizens. In these societies, participation in production media, social exchange and the development of multilingual written communication skills through new computer technologies spread multicultural values. In order to fulfil the social exigencies, it is needed to have the collaboration of research groups for designing and applying international research projects.
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Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial.
Gastroenterology
PUBLISHED: 01-13-2009
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Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis, so it could be an effective therapy for portal hypertension. This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG) and its safety in patients with cirrhosis and portal hypertension.
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Azepane quaternary amino acids as effective inducers of 3(10) helix conformations.
J. Org. Chem.
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A simple method for the synthesis of an azepane quaternary amino acid in enantiopure form is described. Theoretical, NMR, and X-ray studies indicated that this azepane-derived amino acid is an effective stabilizer of 3(10) helical structures in short peptides.
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Making the best of mixed-field orientation of polar molecules: a recipe for achieving adiabatic dynamics in an electrostatic field combined with laser pulses.
Phys. Rev. Lett.
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We have experimentally and theoretically investigated the mixed-field orientation of rotational-state-selected OCS molecules and achieved strong degrees of alignment and orientation. The applied moderately intense nanosecond laser pulses are long enough to adiabatically align molecules. However, in combination with a weak dc electric field, the same laser pulses result in nonadiabatic dynamics of the mixed-field orientation. These observations are fully explained by calculations employing both adiabatic and nonadiabatic (time-dependent) models.
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A pentapeptide signature motif plays a pivotal role in Leishmania DNA topoisomerase IB activity and camptothecin sensitivity.
Biochim. Biophys. Acta
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Leishmania donovani - the causative agent of visceral leishmaniasis - has several evolutionary characteristics that make the disease difficult to combat. Among these differences, a rare heterodimeric DNA topoisomerase IB has been reported thus opening a new promising field in the therapy of leishmaniasis. Several studies of the human enzyme have pointed to the importance of the linker domain in respect to camptothecin sensitivity. At present, it has been impossible to pinpoint the regions that make up the linker domain in Leishmania.
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Advances in modulating thermosensory TRP channels.
Expert Opin Ther Pat
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Thermosensory channels are a subfamily of the transient receptor potential (TRP) channel family that are activated by changes in the environmental temperature. These channels, known as thermoTRPs, cover the entire spectrum of temperatures, from noxious cold (< 15°C) to injurious heat (> 42°C). In addition, dysfunction of these channels contributes to the thermal hypersensitivity that accompanies painful conditions. Moreover, because of their wide tissue and cellular distribution, thermoTRPs are also involved in the pathophysiology of several diseases, from inflammation to cancer.
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Penumbra detection using PWI/DWI mismatch MRI in a rat stroke model with and without comorbidity: comparison of methods.
J. Cereb. Blood Flow Metab.
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Perfusion-diffusion (perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI)) mismatch is used to identify penumbra in acute stroke. However, limitations in penumbra detection with mismatch are recognized, with a lack of consensus on thresholds, quantification and validation of mismatch. We determined perfusion and diffusion thresholds from final infarct in the clinically relevant spontaneously hypertensive stroke-prone (SHRSP) rat and its normotensive control strain, Wistar-Kyoto (WKY) and compared three methods for penumbra calculation. After permanent middle cerebral artery occlusion (MCAO) (WKY n=12, SHRSP n=15), diffusion-weighted (DWI) and perfusion-weighted (PWI) images were obtained for 4 hours post stroke and final infarct determined at 24 hours on T(2) scans. The PWI/DWI mismatch was calculated from volumetric assessment (perfusion deficit volume minus apparent diffusion coefficient (ADC)-defined lesion volume) or spatial assessment of mismatch area on each coronal slice. The ADC-derived lesion growth provided the third, retrospective measure of penumbra. At 1 hour after MCAO, volumetric mismatch detected smaller volumes of penumbra in both strains (SHRSP: 31 ± 50 mm(3), WKY: 22 ± 59 mm(3), mean ± s.d.) compared with spatial assessment (SHRSP: 36 ± 15 mm(3), WKY: 43 ± 43 mm(3)) and ADC lesion expansion (SHRSP: 41 ± 45 mm(3), WKY: 65 ± 41 mm(3)), although these differences were not statistically significant. Spatial assessment appears most informative, using both diffusion and perfusion data, eliminating the influence of negative mismatch and allowing the anatomical location of penumbra to be assessed at given time points after stroke.
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Inpatient Management of Diabetes Mellitus among Noncritically Ill Patients at the University Hospital of Puerto Rico.
Endocr Pract
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Objective: To describe the state of glycemic control in non-critically ill diabetic patients admitted to the Puerto Rico University Hospital, and the adherence to current standard of care guidelines for the treatment of diabetes.Methods: This was a retrospective study of patients admitted to a General Medicine ward with diabetes mellitus as a secondary diagnosis. Clinical data of the first 5 days and the last 24 hours of hospitalization were analyzed.Results: One hundred and forty-seven (147) non-critically ill diabetic patients were evaluated. The rate of hyperglycemia (blood glucose ?180 mg/dL) and hypoglycemia (blood glucose < 70 mg/dL) was 56.7% and 2.8%, respectively. Nearly 60% of patients were hyperglycemic during the first 24 hours of hospitalization (mean random blood glucose 226.5 mg/dL) and 54.2% during the last 24 hours of hospitalization (mean 196.51 mg/dL). Mean random last glucose value before discharge was 189.6 mg/dL. Most patients were treated with subcutaneous insulin, with basal insulin alone (60%) used as the most common regimen. The proportion of patients classified as uncontrolled receiving basal-bolus therapy increased from 54.3% on day 1 to 60.0% on day 5, with 40.0% continuing to receive only basal insulin. Most of the uncontrolled patients had their insulin dose increased (70.1%), however, a substantial portion had no change (23.7%), or even a decrease (6.2%) in their insulin dose.Conclusions: The management of hospitalized diabetic patients is suboptimal, probably due to clinical inertia, manifested by absence of appropriate modification of insulin regimen and intensification of dose in uncontrolled diabetic patients. A comprehensive educational diabetes management program, along with standardized insulin orders, should be implemented to improve the care of these patients.
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