193 research outputs found

    Molecular Modeling, Synthesis, and Antihyperglycemic Activity of the New Benzimidazole Derivatives – Imidazoline Receptor Agonists

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    Artur Martynov,1 Boris Farber,2 Tatyana Bomko,1 Daniel L Beckles,3 Ilya Kleyn4 1Laboratory and Clinical department of Molecular Immunopharmacology, SI “ I. Mechnikov Institute of Microbiology and Immunology of National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine; 2R&D Department, Noigel LLC, New York, NY, USA; 3Baylor Scott & White Health, Round Rock, TX, USA; 4SUNY Downstate Medical Center / University Hospital of Brooklyn, New York, NY, USACorrespondence: Artur Martynov, Email [email protected]: The paper presents the results of a study on the first synthesized benzimidazole derivatives obtained from labile nature carboxylic acids. The synthesis conditions of these substances were studied, their structure was proved, and some components were found to have sugar-reducing activity on the model of alloxan diabetes in rats.Methods: The study used molecular modeling methods such as docking based on the evolutionary model (igemdock), RP_HPLC method to monitor the synthesis reaction, and 1H NMR and 13C NMR, and other methods of organic chemistry to confirm the structures of synthesized substances.Results & Discussion: The docking showed that the ursodeoxycholic acid benzimidazole derivatives have high tropics to all imidazoline receptor carriers (PDB ID: 2XCG, 2bk3, 3p0c, 1QH4). The ursodeoxycholic acid benzimidazole derivative and arginine and histidine benzimidazole derivatives showed the highest sugar-lowering activity in the experiment on alloxan-diabetic rats. For these derivatives, the difference in glucose levels of treated rats was significant against untreated control. Therefore, the new derivatives of benzimidazole and labile natural organic acids can be used to create new classes of imidazoline receptor inhibitors for the treatment of diabetes mellitus and hypertension.Keywords: imidazoline receptors, benzimidazole derivatives, synthesis, antihyperglycemic activit

    Wider sampling reveals a non-sister relationship for geographically contiguous lineages of a marine mussel

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    The accuracy of phylogenetic inference can be significantly improved by the addition of more taxa and by increasing the spatial coverage of sampling. In previous studies, the brown mussel Perna perna showed a sister-lineage relationship between eastern and western individuals contiguously distributed along the South African coastline. We used mitochondrial (COI) and nuclear (ITS) sequence data to further analyze phylogeographic patterns within P.perna. Significant expansion of the geographical coverage revealed an unexpected pattern. The western South African lineage shared the most recent common ancestor (MRCA) with specimens from Angola, Venezuela, and Namibia, whereas eastern South African specimens and Mozambique grouped together, indicating a non-sister relationship for the two South African lineages. Two plausible biogeographic scenarios to explain their origin were both supported by the hypotheses-testing analysis. One includes an Indo-Pacific origin for P.perna, dispersal into the Mediterranean and Atlantic through the Tethys seaway, followed by recent secondary contact after southward expansion of the western and eastern South African lineages. The other scenario (Out of South Africa) suggests an ancient vicariant divergence of the two lineages followed by their northward expansion. Nevertheless, the Out of South Africa hypothesis would require a more ancient divergence between the two lineages. Instead, our estimates indicated that they diverged very recently (310 kyr), providing a better support for an Indo-Pacific origin of the two South African lineages. The arrival of the MRCA of P.perna in Brazil was estimated at 10 [0-40] kyr. Thus, the hypothesis of a recent introduction in Brazil through hull fouling in wooden vessels involved in the transatlantic itineraries of the slave trade did not receive strong support, but given the range for this estimate, it could not be discarded. Wider geographic sampling of marine organisms shows that lineages with contiguous distributions need not share a common ancestry.Portuguese National Science Foundation (FCT) [EXPL/BIA-BIC/1471/2012]; South Africa Research Chairs Initiative (SARChI) of the Department of Science and Technologyinfo:eu-repo/semantics/publishedVersio

    Transnational social capital: the socio‐spatialities of civil society

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    Civil society remains a contested concept, but one that is widely embedded in global development processes. Transnationalism within civil society scholarship is often described dichotomously, either through hierarchical dependency relations or as a more amorphous networked global civil society. These two contrasting spatial imaginaries produce very particular ideas about how transnational relations contribute to civil society. Drawing on empirical material from research with civil society organizations in Barbados and Grenada, in this article I contend that civil society groups use forms of transnational social capital in their work. This does not, however, resonate with the horizontal relations associated with grassroots globalization or vertical chains of dependence. These social relations are imbued with power and agency and are entangled in situated historical, geographical and personal contexts. I conclude that the diverse transnational social relations that are part of civil society activity offer hope and possibilities for continued civil society action in these unexpected spatial arrangements

    Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: An individual-level pooled analysis of 31 cohort studies

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    Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains unknown. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n=168,287) and non-fatal (13 cohorts, n=27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 100,000 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those estimated from cohorts in high-income countries. Funding: Wellcome Trust (214185/Z/18/Z)Fil: Carrillo Larco, Rodrigo M.. Imperial College London; Reino UnidoFil: Stern, Dalia. Instituto Nacional de Salud Publica (insp);Fil: Hambleton, Ian R.. The University Of The West Indies; BarbadosFil: Hennis, Anselm. Pan American Health Organization; Estados UnidosFil: Cesare, Mariachiara Di. Middlesex University; Reino UnidoFil: Lotufo, Paulo. Universidade de Sao Paulo; BrasilFil: Ferreccio, Catterina. Pontificia Universidad Católica de Chile; ChileFil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Perel, Pablo. London School of Hygiene and Tropical Medicine; Reino UnidoFil: Gregg, Edward W. Imperial College London; Reino UnidoFil: Miranda, J. Jaime. Universidad Peruana Cayetano Heredia; PerúFil: Ezzati, Majid. Imperial College London; Reino UnidoFil: Danaei, Goodarz. Harvard Medical School; Estados UnidosFil: Aguilar Salinas, Carlos A.. Instituto Nacional de Ciencias Médicas y Nutrición; MéxicoFil: Alvarez Váz, Ramón. Universidad de la República; UruguayFil: Amadio, Marselle B.. Centro Universitario Senac Santo Amaro; BrasilFil: Baccino, Cecilia. Universidad de la República; UruguayFil: Bambs, Claudia. Pontificia Universidad Católica de Chile; ChileFil: Bastos, João Luiz. Universidade Federal de Santa Catarina; BrasilFil: Beckles, Gloria. Centers for Disease Control and Prevention; Estados UnidosFil: Bernabe Ortiz, Antonio. Universidad Peruana Cayetano Heredia; PerúFil: Bernardo, Carla DO. University of Adelaide; AustraliaFil: Bloch, Katia V.. Universidade Federal do Rio de Janeiro; BrasilFil: Blümel, Juan E.. Universidad de Chile; ChileFil: Boggia, Jose G.. Universidad de la República; UruguayFil: Borges, Pollyanna K.. Universidade Estadual do Ponta Grossa; BrasilFil: Bravo, Miguel. MELISA Institute; ChileFil: Brenes Camacho, Gilbert. Universidad de Costa Rica; Costa RicaFil: Carbajal, Horacio A.. Universidad Nacional de La Plata; ArgentinaFil: Castillo Rascón, María Susana. Universidad Nacional de Misiones; Argentin

    The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

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    <p>Abstract</p> <p>Background</p> <p>The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO<sub>2peak</sub>), patient-reported outcomes, and the organ components that govern VO<sub>2peak </sub>in post-operative non-small cell lung cancer (NSCLC) patients.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO<sub>2peak </sub>for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO<sub>2peak</sub>. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression.</p> <p>Discussion</p> <p>VO<sub>2peak </sub>is becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum.</p> <p>Trial Registration</p> <p>NCT00018255</p
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