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Find video protocols related to scientific articles indexed in Pubmed.
Replacement of berseem hay by Salix tetrasperma on physiological performance of New Zealand White rabbits under subtropical conditions of Egypt.
Trop Anim Health Prod
PUBLISHED: 05-01-2014
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Forty-eight growing New Zealand White male rabbits aged 6 weeks (874?±?1.3 g initial body weight (BW)) were used to study effects of partial replacement of berseem hay (BH) with Salix tetrasperma hay (ST) on growth and physiological responses. Rabbits were allotted to one of four diets of 12 rabbits each for 75 days in a completely randomized design. The treatments were as follows: control (30 % BH), ST25 (7.5 % ST?+?22.5 % BH), ST50 (15 % ST?+?15 % BH), ST75 (22.5 % ST?+?7.5 % BH). Nutrient digestibility coefficients, nutritive value and N utilization of rabbits fed with the ST50 rations were higher (P??ST25 and ST50?>?control. Glucose level was higher (P?
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[Management of bilateral vocal cord paralysis with laser cordectomy].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 04-25-2014
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Bilateral vocal fold paralysis (BVFP) is characterized by fold immobility in complete adduction or abduction, secondary to a vagus nerve lesion, through the recurrent laryngeal nerve. The manifestation is variable dyspnea and stridor, fatal if the airway is not secured. There are endolaryngeal and extralaryngeal techniques to increase the glottic opening, improving ventilation and deglutition, and the possibility of decannulation and phonation.
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Can Conservation Contracts Co-exist with Change? Payment for Ecosystem Services in the Context of Adaptive Decision-Making and Sustainability.
Environ Manage
PUBLISHED: 04-01-2014
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This paper considers the ability of payment for ecosystem services (PES) programs to operate in the context of dynamic and complex social-ecological systems. Drawing on the experiences of two different PES programs in Latin America, we examine how PES institutions fit with the tenets of adaptive decision-making for sustainable resource management. We identify how the program goals and the connection to the market influence the incentive structure, information gathering, learning and feedback processes, and the structure of decision-making rights, specifically the ability to make and modify resource-use rules. Although limited in their generalizability, findings from the two case studies suggest a tension between the contractual model of PES and adaptive decision-making in natural resource systems. PES programs are not inherently decentralized, flexible management tools, as PES contracts tend to restrict decision-making rights and offer minimal flexibility mechanisms to change resource-use practices over the duration of the contract period. Furthermore, PES design and flexibility is heavily dependent on the goals and mission of the buyer and the respective market. If PES is to facilitate sustainable resource management, greater attention is needed to assess how the institutional design of the PES contracts influence the motivation and capacity of participants and program officers alike to adaptively manage the respective resource systems.
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Dual inhibition of the vascular endothelial growth factor pathway: a phase 1 trial evaluating bevacizumab and AZD2171 (cediranib) in patients with advanced solid tumors.
Cancer
PUBLISHED: 02-13-2014
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The current study was conducted to evaluate the safety and biological activity of dual inhibition of the vascular endothelial growth factor (VEGF) pathway with combined bevacizumab and cediranib (a VEGF receptor tyrosine kinase inhibitor).
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Biosimilars 101: considerations for U.S. oncologists in clinical practice.
Cancer Med
PUBLISHED: 02-10-2014
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Biosimilars of biologics used for cancer treatment and supportive care are expected to enter the U.S. market soon. Biosimilars will be highly similar to their reference products, but unlike generic drugs, not identical. Differences between a biosimilar and its reference product may arise because of the complexity of biologics, and differences in the cell lines and processes used during manufacturing. Biosimilars will be approved in the United States through a regulatory pathway based on comparative analytical and clinical studies for their characterization and demonstration of no clinically meaningful differences from their reference products. Unlike generics, initial approval may not include interchangeability, as additional evidence may be required before a biosimilar could be approved as interchangeable with its reference product; interchangeable designation could allow pharmacy-level substitution without prescriber intervention. In some cases, the U.S. Food and Drug Administration (FDA) may extrapolate an indication that has not been formally investigated for the biosimilar but that is approved for the reference product. Robust safety monitoring of all biologics is important to track and accurately attribute adverse events, particularly because their inherent complexity and manufacturing differences make them susceptible to structural changes that can affect safety (e.g., immunogenicity). Accuracy of postapproval safety reports will partly depend on the biosimilar naming approach. Potential cost savings should be evaluated in the context of differences in manufacturers' patient-assistance programs, copayments, and institutional costs. A manufacturer's ability to ensure reliable supply of high-quality biosimilars should also be considered. Broad understanding of these issues is critical for oncologists preparing for their use in clinical practice.
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Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular testing implications.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 01-29-2014
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Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease. Here, we report the prevalence of sequence and structural mutations in these three main recessive genes in Mexican Mestizo patients. The complete sequences of these three genes were analyzed by homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined by multiplex ligation-dependent probe amplification and real-time PCR in 127 patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All individuals had been previously screened for the three most common LRRK2 mutations. The presence of two mutations in compound heterozygous or homozygous genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were observed. Novel mutations were identified in PARK2 and PINK1 genes, including PINK1 duplication for the first time. Exon dosage deletions were the most frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the novel heterozygous and homozygous point mutations in PINK1 observed in familial and sporadic cases from various states of Mexico support the concept that single heterozygous mutations in recessive Parkinson's disease genes play a pathogenic role. These data have important implications for genetic counseling of Mexican Mestizo patients with early-onset Parkinson's disease. The presence of digenic inheritance underscores the importance of studying several genes in this disease. A step-ordered strategy for molecular diagnosis is proposed.
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UV-Vis reflection spectroscopy under variable angle incidence at the air-liquid interface.
Phys Chem Chem Phys
PUBLISHED: 01-22-2014
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The UV-Vis reflection spectroscopy (UV-Vis-RS) in situ at the air-liquid interface provides information about tilt and aggregation of chromophores in Langmuir monolayers. This information is particularly important given in most cases the chromophore is located at the polar region of the Langmuir monolayer. This region of the Langmuir monolayers has been hardly accessible by other experimental techniques. In spite of its enormous potential, the application of UV-Vis-RS has been limited mainly to reflection measurements under light normal incidence or at lower incidence angles than the Brewster angle. Remarkably, this technique is quite sensitive to the tilt of the chromophores at values of incidence angles close to or larger than the Brewster angle. Therefore, a novel method to obtain the order parameter of the chromophores at the air-liquid interface by using s- and p-polarized radiation at different incidence angles is proposed. This method allowed for the first time the experimental observation of the two components with different polarization properties of a single UV-Vis band at the air-liquid interface. The method of UV-Vis spectroscopy under variable angle incidence is presented as a new tool for obtaining rich detailed information on Langmuir monolayers.
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Cascade of access to interventions to prevent HIV mother to child transmission in the metropolitan area of Rio de Janeiro, Brazil.
Braz J Infect Dis
PUBLISHED: 01-02-2014
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To describe the access to the interventions for the prevention of Human Immunodeficiency Virus (HIV) mother to child transmission and mother to child transmission rates in the outskirts of Rio de Janeiro, from 1999 to 2009.
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Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis.
Sci Transl Med
PUBLISHED: 12-06-2013
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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). We have identified and characterized the indolcarboxamides as a new class of antitubercular bactericidal agent. Genetic and lipid profiling studies identified the likely molecular target of indolcarboxamides as MmpL3, a transporter of trehalose monomycolate that is essential for mycobacterial cell wall biosynthesis. Two lead candidates, NITD-304 and NITD-349, showed potent activity against both drug-sensitive and multidrug-resistant clinical isolates of Mtb. Promising pharmacokinetic profiles of both compounds after oral dosing in several species enabled further evaluation for efficacy and safety. NITD-304 and NITD-349 were efficacious in treating both acute and chronic Mtb infections in mouse efficacy models. Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks in exploratory rat toxicology studies revealed a promising safety margin. Finally, neither compound inhibited the activity of major cytochrome P-450 enzymes or the hERG (human ether-a-go-go related gene) channel. These results suggest that NITD-304 and NITD-349 should undergo further development as a potential treatment for multidrug-resistant TB.
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Design, Synthesis, and Biological Evaluation of Indole-2-carboxamides: A Promising Class of Antituberculosis Agents.
J. Med. Chem.
PUBLISHED: 10-22-2013
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Indole-2-carboxamides have been identified as a promising class of antituberculosis agents from phenotypic screening against mycobacteria. One of the hits, indole-2-carboxamide analog (1), had low micromolar potency against Mycobacterium tuberculosis (Mtb), high mouse liver microsomal clearance, and low aqueous solubility. Structure-activity relationship studies revealed that attaching alkyl groups to the cyclohexyl ring significantly improved Mtb activity but reduced solubility. Furthermore, chloro, fluoro, or cyano substitutions on the 4- and 6-positions of the indole ring as well as methyl substitution on the cyclohexyl ring significantly improved metabolic stability. 39 and 41, the lead candidates, displayed improved in vitro activity compared to most of the current standard TB drugs. The low aqueous solubility could not be mitigated because of the positive correlation of lipophilicity with Mtb potency. However, both compounds displayed favorable oral pharmacokinetic properties in rodents and demonstrated in vivo efficacy. Thus, indole-2-carboxamides represent a promising new class of antituberculosis agents.
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para-Aminosalicylic acid is a prodrug targeting dihydrofolate reductase in Mycobacterium tuberculosis.
J. Biol. Chem.
PUBLISHED: 06-18-2013
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para-Aminosalicylic acid (PAS) is one of the antimycobacterial drugs currently used for multidrug-resistant tuberculosis. Although it has been in clinical use for over 60 years, its mechanism(s) of action remains elusive. Here we report that PAS is a prodrug targeting dihydrofolate reductase (DHFR) through an unusual and novel mechanism of action. We provide evidences that PAS is incorporated into the folate pathway by dihydropteroate synthase (DHPS) and dihydrofolate synthase (DHFS) to generate a hydroxyl dihydrofolate antimetabolite, which in turn inhibits DHFR enzymatic activity. Interestingly, PAS is recognized by DHPS as efficiently as its natural substrate para-amino benzoic acid. Chemical inhibition of DHPS or mutation in DHFS prevents the formation of the antimetabolite, thereby conferring resistance to PAS. In addition, we identified a bifunctional enzyme (riboflavin biosynthesis protein (RibD)), a putative functional analog of DHFR in a knock-out strain. This finding is further supported by the identification of PAS-resistant clinical isolates encoding a RibD overexpression mutation displaying cross-resistance to genuine DHFR inhibitors. Our findings reveal that a metabolite of PAS inhibits DHFR in the folate pathway. RibD was shown to act as a functional analog of DHFR, and as for DHFS, both were shown to be associated in PAS resistance in laboratory strains and clinical isolates.
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C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimers disease in type 2 diabetes, a case control study.
Med Clin (Barc)
PUBLISHED: 05-27-2013
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In the last few decades we have witnessed an interesting transformation of the population pyramids throughout the world. As the populations life expectancy increases, there are more chronic diseases such as diabetes mellitus and dementias, and both of them have shown an association.
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Association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in individuals 65 years or more with diabetes from a Geriatric Service in Monterrey, Mexico.
Med Clin (Barc)
PUBLISHED: 04-15-2013
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Cognitive impairment and dementia are common geriatric syndromes in diabetic patients. Inflammation plays a crucial role in the pathophysiology of Alzheimers disease and cognitive impairment. Cyclooxygenases (COX) 1 and 2 participate in inflammation. The polymorphism c.1-765G>C of the COX2 gene might be protective against cognitive decline in Mexicans with diabetes mellitus through its reduced promotor activity. To determine the association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in elderly adults with diabetes.
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From two-dimensional to three-dimensional at the air/water interface: the self-aggregation of the acridine dye in mixed monolayers.
Langmuir
PUBLISHED: 04-08-2013
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The formation of well-defined supramolecular structures on the nanoscopic scale is a fundamental step in nanotechnology. The fine control of the layer-by-layer growth of the supramolecular assemblies at interfaces is most desirable. The collapse of a mixed monolayer composed of two surfactants in an equimolar ratio (the organic dye N-10-dodecyl acridine (DAO) and stearic acid (SA)) is analyzed herein. The collapse process of the DAO/SA mixed monolayer has been monitored using surface pressure-molecular area (?-A) and surface potential isotherms, UV-visible reflection spectroscopy, polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS), Brewster angle microscopy (BAM), and synchrotron-based in situ X-ray reflectivity (XRR) measurements. The collapse of the DAO/SA mixed monolayer leads to an ordered trilayer. The growth of anisotropic 2D domains of micrometric size is observed during the formation of the trilayer, related to the ordering of the acridine polar headgroups. The trilayer is organized with the first and third monolayers displaying the polar headgroups pointing to the aqueous subphase, whereas the intermediate layer displays the polar headgroups pointing to the air. The trilayer is stabilized by the strong self-aggregation acridine dye group of the DAO molecule. The controlled transition from a monolayer to a trilayer described herein is proposed as a model for further interfacial supramolecular structures of tunable thickness comprising organic dyes.
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Evaluation of the structure-activity relationship of rifabutin and analogs: a drug-membrane study.
Chemphyschem
PUBLISHED: 03-15-2013
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This work focuses on the influence of rifabutin and two novel analogs, namely, N-acetyl-rifabutin and N-butanoyl-rifabutin, on the biophysical properties of lipid membranes. Monolayers and multilamellar vesicles composed of egg L-?-phosphatidylcholine:cholesterol in a molar ratio of 4:1 are chosen to mimic biological membranes. Several accurate biophysical techniques are used to establish a putative relationship between the chemical structure of the antimycobacterial compounds and their activity on the membranes. A combination of in situ experimental techniques, such as Langmuir isotherms, Brewster angle microscopy, polarization-modulated infrared reflection-absorption spectroscopy, and small-angle X-ray scattering, is used to assess the drug-membrane interaction. A relationship between the effect of a drug on the organization of the membranes and their chemical structure is found and may be useful in the development of new drugs with higher efficacy and fewer toxic effects.
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Insights about ?-tocopherol and Trolox interaction with phosphatidylcholine monolayers under peroxidation conditions through Brewster angle microscopy.
Colloids Surf B Biointerfaces
PUBLISHED: 03-11-2013
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Membranes are major targets to oxidative damage, particularly due to lipid oxidation, which has been associated to aging. The role, efficacy and membrane interaction of antioxidants is still unclear, requiring further understanding of molecular interaction. Hence, the objective of this work was to evaluate the interaction between antioxidants (?-tocopherol and its aqueous soluble analog Trolox) and the monolayer formed by phosphatidylcholine molecules at air/liquid interface upon peroxidation conditions, promoted by peroxyl radicals from thermal decomposition of 2,2-azobis(2-methylpropionamidine) (AAPH). The interaction with three different monolayers, containing (i) 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC), (ii) DDPC+?-linolenic acid, or (iii) egg yolk l-?-phosphatidylcholine (EPC), was ascertain by surface pressure (?)-molecular area (A) isotherms and by monitoring monolayer features through Brewster angle microscopy (BAM). The interaction of antioxidants with DPPC monolayers was confirmed by modifications on DPPC domain shape for ?-tocopherol and through the maintenance of typical multilobed domain shape during an extended surface pressure interval for Trolox. Under peroxidation conditions, BAM images showed a clear interaction between components of AAPH subphase with the monolayer through changes on DPPC domain shape and appearance of white dots, located mainly at the frontier between the condensed and expanded liquid phases. White branched structures were also observed whenever both ?-linolenic acid and ?-tocopherol were present, indicating the segregation of these components within the monolayer, which is highly significant in biological systems. For EPC monolayers, no information from BAM was obtained but ?-A isotherms confirmed the existence of the same interactions observed within the other two monolayers.
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Effects of a novel antimycobacterial compound on the biophysical properties of a pulmonary surfactant model membrane.
Int J Pharm
PUBLISHED: 02-23-2013
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In this work, the interactions of a novel rifabutins analogue (N-acetyl-rifabutin, RFB2) with two-dimensional (Langmuir monolayers) and three-dimensional (large unilamellar and multilamellar vesicles) membrane models of the pulmonary surfactant (PS) were evaluated. The main purpose of this study is to obtain detailed information at the molecular level between the interactions of RFB2 with the phospholipids of the PS, under physiological conditions. Therefore, the effects of RFB2 in the monolayer phase behaviour at the air-water interface and in the lipid bilayer of membrane models composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) have been systematically compared. In this context, several biophysical techniques were carried out to establish the interactions of RFB2 with the two-dimensional membrane models of the PS: Langmuir isotherms, Brewster angle microscopy (BAM), and polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS); and with three-dimensional membrane models of the PS: derivate spectrophotometry partition coefficient (Kp), dynamic light scattering (DLS), small and wide angle X-ray scattering (SAXS and WAXS). The results gathered by the different biophysical techniques and the PS membrane model used provide detailed information about the strong interactions of RFB2 with the polar head groups of the PS phospholipids and permit to establish the impact of the RFB2-PS membrane interactions, justifying an often unexplored biophysical approach to the drugs pharmacokinetics and toxicological effect.
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The use of factorial design, image analysis, and an efficiency calculation for multiplex PCR optimization.
J. Clin. Lab. Anal.
PUBLISHED: 02-04-2013
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The quality of multiplex polymerase chain reaction (PCR) assays depends on several factors. Therefore, it is important to establish the optimal conditions to achieve efficient amplification. The objective of this study was to implement a 5 × 4 factorial design combined with image analysis using agarose gels and an efficiency calculation to optimize a multiplex PCR assays for the detection of Salmonella enterica serovar typhimurium.
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Self-assembly of Acridine Orange into H-aggregates at the air/water interface: tuning of orientation of headgroup.
Langmuir
PUBLISHED: 11-16-2011
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The surface active derivative of the organic dye Acridine Orange (N-10-dodecyl-acridine orange (DAO)) has been included in mixed Langmuir monolayers with stearic acid (SA). The maximum relative content on DAO for a stable mixed monolayer is a molar ratio of X(DAO) = 0.5. Brewster angle microscopy (BAM) reveals a high homogeneity at the micrometer level for the mixed monolayer in equimolar proportion (X(DAO) = 0.5), whereas the appearance of domains occurs for lower content of DAO, i.e., X(DAO) = 0.2 and 0.1. The aggregation of the DAO headgroup leads to well-defined H-aggregates at the air/water interface for those mixed monolayers with a low content of DAO. However, for the mixed monolayers enriched in DAO, e.g., X(DAO) = 0.5, the molecular crowding prevents the formation of defined supramolecular structures. Molecular organization and tilting of the DAO headgroup is quantitatively analyzed by in situ UV-visible reflection spectroscopy. The formation of H-aggregates of the DAO headgroup can be reversibly tuned with the applied surface pressure. A molecular mechanism for the conformational rearrangement of the DAO molecule is proposed using RM1 quantum semiempirical calculations.
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Chiral textures inside 2D achiral domains.
J. Am. Chem. Soc.
PUBLISHED: 11-03-2011
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Chiral interfaces are of capital importance for biorecognition processes and nanotechnology. In this work, a mixed Langmuir monolayer was built using a surface-active dye and a phospholipid. The monolayer displayed optical activity. The driving force for the formation of the supramolecular chirality is the self-assembly of the polar headgroups of the dye. The existence of supramolecular chirality inside nonchirally-shaped domains is shown.
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T cell monitoring of chemotherapy in experimental rat tuberculosis.
Antimicrob. Agents Chemother.
PUBLISHED: 05-31-2011
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Mycobacterium tuberculosis is the causative agent of a pulmonary epidemic that is estimated to infect one-third of the worlds population and that has an increased incidence of multidrug resistance. The evaluation of new chemical entities against M. tuberculosis is hampered by the lack of biological tools to help predict efficacy, from early drug development to clinical trials. As the rat is the animal species of choice in the pharmaceutical industry, we have developed a rat model of acute and chronic phases of M. tuberculosis infection for drug efficacy testing. In this model, we have evaluated the impact of tuberculosis drugs on T cell response using the enzyme-linked immunospot assay methodology. Infected rats treated with isoniazid (INH) or rifampin (RIF) responded to therapy, the potency of which was comparable to that seen in the mouse. Peripheral blood mononuclear cells from infected rats produced gamma interferon (IFN-?) in response to RD-1 antigens, such as the 6-kDa early secretory antigen target (ESAT-6) and the 10-kDa culture filtrate protein (CFP-10). A decrease in IFN-? spot-forming cells (SFCs) was consistently observed in response to drug treatment. In both the acute- and chronic-phase models, the T cell response was more sensitive to ESAT-6 than to CFP-10. The SFC count in response to ESAT-6 appears to be an indicator of bacterial killing in the rat. Collectively, our data suggest that the ESAT-6 response could be used as a potential surrogate of drug efficacy in the rat and that such a readout could help shorten drug testing during preclinical development.
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Experimental tuberculosis in the Wistar rat: a model for protective immunity and control of infection.
PLoS ONE
PUBLISHED: 03-14-2011
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Despite the availability of many animal models for tuberculosis (TB) research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb) infection.
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Retrospective analysis of satraplatin in patients with metastatic urothelial cancer refractory to standard platinum-based chemotherapy.
Clin Genitourin Cancer
PUBLISHED: 03-04-2011
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Satraplatin is a novel platinum agent with favorable clinical attributes including oral bioavailability and lack of significant treatment-associated neuropathy and nephropathy. Furthermore, preclinical studies have shown that satraplatin is active is cisplatin-resistant tumors. We retrospectively evaluated the activity of satraplatin in patients with cisplatin or carboplatin-refractory urothelial carcinoma and demonstrated lack of significant antitumor activity in this population.
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J-aggregation of a sulfonated amphiphilic porphyrin at the air-water interface as a function of pH.
J Colloid Interface Sci
PUBLISHED: 01-17-2011
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?-A isotherms, ellipsometric measurements, Brewster angle microscopy (BAM) and reflection spectroscopy have been utilized to characterize the films of an amphiphilic porphyrin ((OD)(3)TPPS(3)) at the air-water interface as a function of pH. This porphyrin forms stable mono-molecular layers at such interfaces, and exhibits different J-aggregation as a function of pH. The J-aggregation of (OD)(3)TPPS(3) on neutral pH subphases is notable considering that the nitrogen atoms at the central macrocycle have a pK(a)?4.9. The type of aggregates at neutral pH is like those detected at pH<4, because the central porphyrin ring is already protonated. However at basic pH the aggregation happens without protonation of the central ring but can be instead controlled by application of the surface pressure. At the air-water interface, (OD)(3)TPPS(3) shows two bands, a red component and a blue component, which have characteristics of non-degenerate linear oscillators being perpendicularly polarized between each other. The spectral behavior observed on subphases at different pHs is qualitatively interpreted by means of exciton coupling theory, assuming that the degenerate transitions attributed to the Soret band are split. Additionally, highly oriented molecular films of these J-aggregates were deposited onto transparent quartz slides.
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Phase I Dose Escalation Study of Sodium Stibogluconate (SSG), a Protein Tyrosine Phosphatase Inhibitor, Combined with Interferon Alpha for Patients with Solid Tumors.
J Cancer
PUBLISHED: 01-14-2011
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Purpose: Sodium stibogluconate (SSG), a small molecule inhibitor of protein tyrosine phosphatases, combined with IFN-alpha-2b (IFN-?) inhibited solid tumor cell line growth in vitro. We conducted a phase I clinical trial with SSG plus IFN-? in advanced cancer patients to assess tolerance, maximum tolerated dose (MTD) and immune system effects.Experimental Design: SSG was administered intravenously alone for five days of week 1, cycle 1 (21 days per cycle) and together with IFN-? 2b s (3 million units sc TIW) in week 2, and after a rest during week 3, on a 2-week on/1-week off cycle. SSG dose levels were 400, 600, 900, 1125, and 1350 mg/m(2).Results: Twenty-four patients were studied. Common toxicities included asymptomatic elevated serum lipase, thrombocytopenia, fatigue, fever, chills and anemia. The dose-limiting toxicities (DLT) were hypokalemia, thrombocytopenia, fatigue, pancreatitis and skin rash. The MTD was 900 mg/m(2 )SSG and IFN-?, 3 million units TIW. At this dose, patients had a significantly lower number of regulatory T cells (T(R )Cells) (p = 0.012), myeloid dendritic cells (mDC) (p = 0.028); higher percentage of natural killer (NK) cells that synthesized perforin (p = 0.046) and of plasmacytoid dendritic cells (pDC) that secreted IFN-? (p = 0.018) in response to activation through toll-like receptor (TLR) 7 and TLR 8 by CL097, the highly water-soluble derivative of the imidazoquinoline compound R848.Conclusions: SSG in combination with IFN-? 2b was well tolerated and augmented cellular immune parameters.
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Molecular organization and effective energy transfer in iridium metallosurfactant-porphyrin assemblies embedded in Langmuir-Schaefer films.
Phys Chem Chem Phys
PUBLISHED: 12-14-2010
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Mixed Langmuir monolayers and Langmuir-Schaefer (LS) films containing the cationic metallosurfactant bis(2-phenylpyridine)(4,4-diheptadecyl-2,2-bipyridine)-iridium(III) chloride (Ir-complex) and the anionic tetrakis(4-sulfonatophenyl)porphyrin (TSPP) in 4:1 molar ratio have been successfully prepared by the co-spreading method at the air-water interface. The presence of both luminescent species at the interface, as well as the organization of the TSPP underneath the Ir-complex matrix in Langmuir and LS films, is inferred by surface techniques such as ?-A isotherms, reflection spectroscopy, Brewster angle microscopy (BAM) and UV-visible absorption spectroscopy. A red-shift in the absorption band of the porphyrin under the compression of the mixed monolayer suggests the J-aggregation of the TSPP under the Ir-complex matrix. To date, this is the first report of Langmuir and/or LS films containing these two types of species together. Furthermore, the intermolecular energy transfer between Ir-complex and TSPP molecules in solution and in transferred mixed films is investigated through steady-state fluorescence and lifetime measurements. These results indicate that effective intermolecular energy transfer occurs from the Ir-complex to the TSPP molecules in LS films. The influence of the spatial proximity of donor and acceptor molecules has been studied by the insertion of lipid interlayers among them.
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Exploratory study of hepatic arterial infusion oxaliplatin with systemic 5-fluorouracil/bevacizumab in patients with refractory solid tumor and extensive liver metastases.
Clin Colorectal Cancer
PUBLISHED: 12-08-2010
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This pilot clinical trial explored the feasibility, safety, and efficacy of regional hepatic therapy combined with systemic anticancer agents in patients with refractory solid tumors and extensive unresectable liver involvement, including those with compromised hepatic function.
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Nitrate respiration protects hypoxic Mycobacterium tuberculosis against acid- and reactive nitrogen species stresses.
PLoS ONE
PUBLISHED: 06-23-2010
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There are strong evidences that Mycobacterium tuberculosis survives in a non-replicating state in the absence of oxygen in closed lesions and granuloma in vivo. In addition, M. tuberculosis is acid-resistant, allowing mycobacteria to survive in acidic, inflamed lesions. The ability of M. tuberculosis to resist to acid was recently shown to contribute to the bacillus virulence although the mechanisms involved have yet to be deciphered. In this study, we report that M. tuberculosis resistance to acid is oxygen-dependent; whereas aerobic mycobacteria were resistant to a mild acid challenge (pH 5.5) as previously reported, we found microaerophilic and hypoxic mycobacteria to be more sensitive to acid. In hypoxic conditions, mild-acidity promoted the dissipation of the protonmotive force, rapid ATP depletion and cell death. Exogenous nitrate, the most effective alternate terminal electron acceptor after molecular oxygen, protected hypoxic mycobacteria from acid stress. Nitrate-mediated resistance to acidity was not observed for a respiratory nitrate reductase NarGH knock-out mutant strain. Furthermore, we found that nitrate respiration was equally important in protecting hypoxic non-replicating mycobacteria from radical nitrogen species toxicity. Overall, these data shed light on a new role for nitrate respiration in protecting M. tuberculosis from acidity and reactive nitrogen species, two environmental stresses likely encountered by the pathogen during the course of infection.
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A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver.
Cancer
PUBLISHED: 06-22-2010
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Liver metastases in patients with cancer are associated with poor survival. The authors of this report conducted a phase 1 study of hepatic arterial infusion (HAI) oxaliplatin combination therapy in patients with advanced cancer and liver metastases.
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Methylene blue adsorption on a DMPA lipid langmuir monolayer.
Chemphyschem
PUBLISHED: 06-15-2010
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Adsorption of methylene blue (MB) onto a dimyristoylphosphatidic acid (DMPA) Langmuir air/water monolayer is studied by molecular dynamics (MD) simulations, UV reflection spectroscopy and surface potential measurements. The free-energy profile associated with MB transfer from water to the lipid monolayer shows two minima of -66 and -60 kJ mol(-1) for its solid and gas phase, respectively, corresponding to a spontaneous thermodynamic process. From the position of the free-energy minima, it is possible to predict the precise location of MB in the interior of the DMPA monolayer. Thus, MB is accommodated in the phosphoryl or carbonyl region of the DMPA Langmuir air/water interface, depending on the isomorphic state (solid or gas phase, respectively). Reorientation of MB, measured from the bulk solution to the interior of the lipid monolayer, passes from a random orientation in bulk solution to an orientation parallel to the surface of the lipid monolayer when MB is absorbed.
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Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma.
J Transl Med
PUBLISHED: 05-27-2010
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Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing.
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Quantitative phase microscopy using defocusing by means of a spatial light modulator.
Opt Express
PUBLISHED: 04-15-2010
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A new method for recovery the quantitative phase information of microscopic samples is presented. It is based on a spatial light modulator (SLM) and digital image processing as key elements to extract the samples phase distribution. By displaying a set of lenses with different focal power, the SLM produces a set of defocused images of the input sample at the CCD plane. Such recorded images are then numerically processed to retrieve phase information. This iterative process is based on the wave propagation equation and leads on a complex amplitude image containing information of both amplitude and phase distributions of the input sample diffracted wave front. The proposed configuration is a non-interferometric architecture (conventional transmission imaging mode) where no moving elements are included. Experimental results perfectly correlate with the results obtained by conventional digital holographic microscopy (DHM).
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A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy.
Nat Commun
PUBLISHED: 04-06-2010
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Candidate antibacterials are usually identified on the basis of their in vitro activity. However, the apparent inhibitory activity of new leads can be misleading because most culture media do not reproduce an environment relevant to infection in vivo. In this study, while screening for novel anti-tuberculars, we uncovered how carbon metabolism can affect antimicrobial activity. Novel pyrimidine-imidazoles (PIs) were identified in a whole-cell screen against Mycobacterium tuberculosis. Lead optimization generated in vitro potent derivatives with desirable pharmacokinetic properties, yet without in vivo efficacy. Mechanism of action studies linked the PI activity to glycerol metabolism, which is not relevant for M. tuberculosis during infection. PIs induced self-poisoning of M. tuberculosis by promoting the accumulation of glycerol phosphate and rapid ATP depletion. This study underlines the importance of understanding central bacterial metabolism in vivo and of developing predictive in vitro culture conditions as a prerequisite for the rational discovery of new antibiotics.
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Phase I clinical trial of hepatic arterial infusion of cisplatin in combination with intravenous liposomal doxorubicin in patients with advanced cancer and dominant liver involvement.
Cancer Chemother. Pharmacol.
PUBLISHED: 02-01-2010
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We conducted a phase I study of hepatic arterial infusion (HAI) cisplatin and systemic chemotherapy in patients with advanced cancer and dominant liver involvement.
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Chemokine expression in tumor-to-tumor metastasis.
Oncol Lett
PUBLISHED: 01-26-2010
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Chemokines play an important role in cancer metastasis by modulating the directional cell movement and migration of tumor cells. The most commonly overexpressed chemokine receptor in human cancer is CXCR4. Once activated by its ligand CXCL12 (stromal cell-derived factor-1 ligand/SDF1), CXCR4 stimulates several key migratory, proliferative and survival signaling cellular pathways. CXCR4 is expressed in small-cell lung carcinoma (SCLC) cells and other tumors. To further characterize the role of chemokines in tumor-to-tumor metastasis, we analyzed the tissue expression of CXCR4 and CXCL12 in the surgical specimen of a patient with this phenomenon. We performed immunohistochemical analysis for the expression of CXCR4 and CXCL12 in metastatic tumor tissue of a 69-year-old Caucasian male with extensive SCLC metastatic to a renal oncocytoma. The oncocytoma tissue harboring SCLC showed CXCL12 expression, but not CXCR4. A high expression of the two molecules was found in a normal renal parenchymal control. Our results suggest that CXCR4 and CXCL12 plays a role in this condition, but their expression may be affected by the microenvironment of the harboring malignancy. Further characterization of these phenomena is needed to shed light on the biological mechanisms of tumor metastasis.
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Semifluorinated thiols in Langmuir monolayers.
J Colloid Interface Sci
PUBLISHED: 01-06-2010
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A series of semifluorinated thiols of the general formula CF(3)(CF(2))(m-1)(CH(2))(n)SH (abbreviated to FmHnSH) have been synthesized and the Langmuir monolayers thoroughly characterized using surface pressure (?) and electric surface potential (?V) measurements. These data have been complemented with Brewster angle microscopy (BAM) visualization of the monolayers structure and IR spectroscopy (PM-IRRAS) analysis of the alkyl chain conformation. The investigated thiols (namely F4H10SH, F8H6SH, F6H10SH, F10H6SH, F6H11SH, F8H10SH and F10H10SH) differ in the length of the hydrophobic chain as well as in the degree of fluorination. Although the -SH group cannot form strong hydrogen bonds with the water subphase, thereby causing only weak anchoring, it has been found that all the investigated thiols, except for F4H10SH, are capable of stable Langmuir monolayer formation. The investigated thiols can be divided into two categories - thiols with longer alkyl chain (F10H10SH, F10H6SH, F8H10SH) and compounds with shorter hydrophobic part (F6H10SH, F6H11SH, F8H6SH). The monolayers of the latter thiols have their equilibrium surface pressure (ESP) comparable with the collapse pressure (?(C)) of their monolayers; thus these films are stable within the whole range of compression. On the contrary, thiols with longer perfluorinated fragments have considerably lower ESP than the ?(C) of their monolayers; therefore, both stable and metastable regions can be distinguished in their ?-A isotherms. Interestingly, for F8H6SH, a smectic ordering of molecules can be observed in monolayers as visualized with BAM. By comparing film-forming properties of the studied semifluorinated thiols with previously studied semifluorinated alkanes it has been found that the presence of -SH group facilitates spreading at the free water surface. Semifluorinated thiols have been found to maintain their monomolecular ordering in the presence of heavy metal cations in the aqueous subphase, contrary to their hydrogenated analogues, which have been reported to crystallize under the same conditions.
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Reversible collapse of insoluble monolayers: new insights on the influence of the anisotropic line tension of the domain.
J Phys Chem B
PUBLISHED: 10-02-2009
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In this paper, we study the collapse of a mixed insoluble monolayer formed by a cationic matrix, dioctadecyl-dimethylammonium bromide (DOMA), and a tetra-anionic porphyrin, tetrakis(4-sulfonatophenyl)porphyrin (TSPP), in a molar ratio TSPP/DOMA = 1:4. During the collapse of this system, we visualized the formation of circular domains consisting exclusively of trilayer, although the domains coalescence was not observed. The coexistence of trilayer and monolayer at the final step of the collapse cannot be interpreted exclusively in terms of a thermodynamic phase equilibrium, intervening as an additional factor the anisotropic line tension of the domain. A high line tension implies a high resistance to the domain deformation, and the anisotropy of the line tension implies the lack of coalescence between these domains, which has been experimentally observed by Brewster angle microscopy for us. Under these circumstances, the domains of collapsed material could enclose monolayer regions where the local surface pressure drops thus stopping the collapse process. The collapse of the TSPP/DOMA system is reversible, that is, the return of the three-dimensional material to the monolayer fits into a simple kinetics according to the nucleation-growth-collision theory. As for the collapse, the reverse process is also affected by the line tension of the domains. This paper relates the high line tension and the anisotropic line tension of a given domains with the reversible nature of the collapse process.
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A phase I clinical trial of darinaparsin in patients with refractory solid tumors.
Clin. Cancer Res.
PUBLISHED: 07-07-2009
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Darinaparsin, an organic arsenic, targets essential cell survival pathways. We determined the dose-limiting toxicity (DLT) and maximum tolerated dose of darinaparsin in patients with advanced cancer.
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Phase I study of the combination of docetaxel, temozolomide and cisplatin in patients with metastatic melanoma.
Cancer Chemother. Pharmacol.
PUBLISHED: 05-27-2009
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In a search for more effective combination chemotherapy for the treatment of metastatic melanoma, we conducted a phase I trial of a novel combination of docetaxel, temozolomide, and cisplatin.
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Seroepidemiological study of human parvovirus B19 among human immunodeficiency virus-infected patients in a medium-sized city in Rio de Janeiro, Brazil.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 04-27-2009
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Parvovirus B19 (B-19) may cause chronic anaemia in immunosuppressed patients, including those infected with human immunodeficiency virus (HIV). We studied single serum samples from 261 consecutive HIV-infected patients using an enzyme immunoassay to detect IgG antibodies to B-19. The seroprevalence of B-19-IgG was 62.8%. The differences in seroprevalence across gender, age, educational categories, year of collection of the serum samples, clinical and antiretroviral therapy characteristics, CD4+ count, CD4+ and CD8+ percentage and CD4+/CD8+ ratios were neither substantial nor statistically significant. There was a non-significant, inverse association between B-19 seropositivity and plasma HIV load and haemoglobin level. Our results indicated that 37.1% of patients might be susceptible to B-19 infection and remained at risk for being infected, mainly during epidemic periods. As B-19 infection can be treated with immune globulin preparations, it may be included in the diagnostic approach toward chronic anaemia in HIV-infected patients.
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Phase I/II trial of tremelimumab in patients with metastatic melanoma.
J. Clin. Oncol.
PUBLISHED: 01-12-2009
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Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with tremelimumab (CP-675,206), a fully human anti-CTLA4 monoclonal antibody, was tolerated and demonstrated antitumor activity in a single dose, dose-escalation phase I trial in patients with solid tumors. This phase I/II trial was conducted to examine safety of multiple doses of tremelimumab, to further assess efficacy, and to identify an appropriate dosing regimen for further development.
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Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease.
Biochim. Biophys. Acta
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This work focuses on the interaction of mycolic acids (MAs) and two antimycobacterial compounds (Rifabutin and N-acetyl-Rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. For this purpose, accurate biophysical techniques (Langmuir isotherms, Brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: MAs mimic bacterial lipids of the Mycobacterium tuberculosis (MTb) membrane, whereas Curosurf® was used as the human pulmonary surfactant (PS) membrane model. The results obtained show that high quantities of MAs are responsible for significant changes on PS biophysical properties. At the dynamic inspiratory surface tension, high amounts of MAs decrease the order of the lipid monolayer, which appears to be a concentration dependent effect. These results suggest that the amount of MAs might play a critical role in the initial access of the bacteria to their targets. Both molecules also interact with the PS monolayer at the dynamic inspiratory surface. However, in the presence of higher amounts of MAs, both compounds improve the phospholipid packing and, therefore, the order of the lipid surfactant monolayer. In summary, this work discloses the putative protective effects of antimycobacterial compounds against the MAs induced biophysical impairment of PS lipid monolayers. These protective effects are most of the times overlooked, but can constitute an additional therapeutic value in the treatment of pulmonary tuberculosis (Tb) and may provide significant insights for the design of new and more efficient anti-Tb drugs based on their behavior as membrane ordering agents.
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Molecular interaction of Rifabutin on model lung surfactant monolayers.
J Phys Chem B
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Tuberculosis is one of the most relevant problems for global health care. The design of new drugs against tuberculosis is aimed at maximizing impact against the disease, as well as minimizing the toxicological effect on the lung surfactant. In this work, the antituberculosis drug Rifabutin is studied in combination with phospholipid Langmuir monolayers as models of the lung surfactant monolayer. The zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and the anionic 1,2-dipalmitoyl-sn-glycero-3-phospho-(1-rac-glycerol) (DPPG) were used as model phospholipids. A combination of in situ experimental techniques of Brewster angle microscopy, polarization-modulated infrared reflection-absorption spectroscopy, and UV-vis reflection spectroscopy with computer simulations has been used. The interactions between Rifabutin and the DPPC and DPPG Langmuir monolayers were described as the formation of an inclusion complex. The phospholipid-Rifabutin inclusion complex prevents the penetration of the Rifabutin into the alkyl chain region of the phospholipids, leading to a disruption of the monolayer structure and a possible toxicological effect.
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Langmuir monolayers of an inclusion complex formed by a new calixarene derivative and fullerene.
Langmuir
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The design of new molecules with directed interactions to functional molecules as complementary building blocks is one of the main goals of supramolecular chemistry. A new p-tert-butylcalix[6]arene monosubstituted derivative bearing only one alkyl chain with an acid group (C6A3C) has been synthesized. The C6A3C has been successfully used for building Langmuir monolayers at the air-water interface. The C6A3C molecule adopts a flatlike orientation with respect to the air-water interface. The molecular structure gives the molecule amphiphilic character, while allowing the control of both the dissociation degree and the molecular conformation at the air-water interface. The C63AC has been combined with pristine fullerene (C60) to form the supramolecular complex C6A3C:C60 in 2:1 molar ratio (CFC). The CFC complex retains the ability of C6A3C to form Langmuir monolayers at the air/water interface. The interfacial molecular arrangement of the CFC complex has been convincingly described by in situ UV-vis reflection spectroscopy and synchrotron X-ray reflectivity measurements. Computer simulations complement the experimental data, confirming a perpendicular orientation of the calixarene units of CFC with respect to the air-water interface. This orientation is stabilized by the formation of intermolecular H-bonds. The interfacial monolayer of the CFC supramolecular complex is proposed as a useful model for the well-defined self-assembly of recognition and functional building blocks.
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High frequency of Parkin exon rearrangements in Mexican-mestizo patients with early-onset Parkinsons disease.
Mov. Disord.
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Parkin mutations in patients with early-onset Parkinsons disease (EOPD) are estimated to occur in 49% of familial cases and 18% of sporadic cases.
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A randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanoma.
Melanoma Res.
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Cilengitide (EMD 121974) is a selective inhibitor of integrins ?v?3 and ?v?5. The ?v?3 promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells. We conducted a randomized phase II trial in patients with metastatic melanoma to evaluate the clinical efficacy of cilengitide. Patients with stage IV or unresectable stage III melanoma who were either chemonaive or who had previously received one systemic therapy were enrolled. Patients were randomly assigned to either 500 or 2000 mg of cilengitide administered intravenously twice weekly. The primary aim of this study was to determine the progression-free survival rate at 8 weeks. Tumor samples and blood samples were collected for pharmacodynamic and pharmacokinetic studies. Twenty-nine patients were enrolled, of whom 26 were treated (14 at 500 mg and 12 at 2000 mg). Among those treated, only three were progression free at 8 weeks: two in the 500 mg arm and one in the 2000 mg arm. One patient in the 2000 mg arm showed a prolonged partial response after an initial 28% enlargement of her target lesions. The treatment was well tolerated without clinically significant adverse events. The sole responder and one of two patients with stable disease had no ?v?3 expression at baseline. Overall, ?v?3 expression was decreased by day 8 of the treatment (P=0.05). Cilengitide was well tolerated by patients in both the treatment arms but had minimal clinical efficacy as a single-agent therapy for metastatic melanoma, and the efficacy was not related to baseline ?v?3 expression.
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Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
N. Engl. J. Med.
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Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the hosts immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models.
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A high-throughput screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis.
ACS Chem. Biol.
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Growing evidence suggests that the presence of a subpopulation of hypoxic non-replicating, phenotypically drug-tolerant mycobacteria is responsible for the prolonged duration of tuberculosis treatment. The discovery of new antitubercular agents active against this subpopulation may help in developing new strategies to shorten the time of tuberculosis therapy. Recently, the maintenance of a low level of bacterial respiration was shown to be a point of metabolic vulnerability in Mycobacterium tuberculosis. Here, we describe the development of a hypoxic model to identify compounds targeting mycobacterial respiratory functions and ATP homeostasis in whole mycobacteria. The model was adapted to 1,536-well plate format and successfully used to screen over 600,000 compounds. Approximately 800 compounds were confirmed to reduce intracellular ATP levels in a dose-dependent manner in Mycobacterium bovis BCG. One hundred and forty non-cytotoxic compounds with activity against hypoxic non-replicating M. tuberculosis were further validated. The resulting collection of compounds that disrupt ATP homeostasis in M. tuberculosis represents a valuable resource to decipher the biology of persistent mycobacteria.
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Diagnosis of adult-type hypolactasia/lactase persistence: genotyping of single nucleotide polymorphism (SNP C/T-13910) is not consistent with breath test in Colombian Caribbean population.
Arq Gastroenterol
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Genotyping of single nucleotide polymorphism (SNP C/T(-13910)) located upstream of the lactase gene is used to determine adult-type hypolactasia/lactase persistence in North-European Caucasian subjects. The applicability of this polymorphism has been studied by comparing it with the standard diagnostic methods in different populations.
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Revisiting the Brewster Angle Microscopy: the relevance of the polar headgroup.
Adv Colloid Interface Sci
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The Brewster Angle Microscopy (BAM) is a powerful microscopy technique allowing the in situ visualization of the morphology of Langmuir monolayers at the air/water interface. The use of the BAM for attaining structural insights in the molecular arrangement of the Langmuir monolayers is widespread. In this review, we examine the reflection of a Langmuir monolayer under a rather different perspective than classical: the influence of the polar headgroup of the amphiphiles in the BAM images is taken into account. The relevance of the polar headgroup as the main cause of the BAM features has been the focus of a reduced number of BAM studies. An emerging experimental and theoretical framework from recent bibliography is discussed. Different theoretical scenarios are considered, concerning the size and absorption of radiation of the polar headgroup. Two qualitative examples showing physical phenomena regarding the reflectivity changes in a BAM experiments are discussed. The anisotropy in the BAM images as inner textures is of special interest. Quantitative structural information of the molecular arrangement of the monolayer is obtained by simulating the textures of the domains observed. The quantitative assessment of the detailed molecular arrangement of the polar headgroup by BAM is highly valuable, as this information can hardly be obtained from other experimental techniques. The procedure for extracting quantitative structural data from the experimental BAM pictures is revised in detail from the recent bibliography for further application of this model to different Langmuir monolayers.
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Anthelmintic effects of Salix babylonica L. and Leucaena leucocephala Lam. extracts in growing lambs.
Trop Anim Health Prod
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Twenty Katahdin?×?Pelibuey crossbreed male lambs, 3 to 4 months of age and 24?±?0.3 kg of body weight, were used to study the anthelmintic effects of administering extracts of Salix babylonica L. (SB) and Leucaena leucocephala Lam. (LL). Lambs had not been treated with anthelmintics previously and were randomly allocated into four groups of five lambs each in a completely randomized design. Treatments were as follows: control (lambs fed on total mixed ration without extracts), SB (as control plus S. babylonica L. extract at 30 ml/day), LL (as control plus L. leucocephala Lam. extract at 30 ml/day), and SBLL (as control plus 30 ml/day of S. babylonica L. and L. leucocephala Lam. extracts in a 1:1 (v/v) mixture) for 63 days. Extracts were orally administered before the 8:00 a.m. feeding to each lamb. Rectal fecal samples were collected from each lamb at day 22 (P1), day 43 (P2), and day 63 (P3) of the experiment. Adult worm and egg counts were determined in each fecal sample immediately after collection. Plant secondary metabolites of total phenolics, saponins, and the aqueous fraction were 50 % lower in the SB versus LL extracts. Overall, the oral administration of extracts has improved the egg and worm count reductions in lamb feces by 54, 47, and 40 % for LL, SB, and SBLL, respectively, versus the control lambs. Reductions of worm egg counts in lamb feces were higher (P?
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