Adipocitoquinas y síndrome metabólico : rol de la vistafina en la patogenia de enfermedad cardiovascular

La enfermedad cardiovascular es la primera causa de morbi-mortalidad en los países industrializados. El síndrome metabólico, caracterizado por hipertensión, dislipidemia, obesidad e hiperglucemia, constituye el principal factor de riesgo para la enfermedad cardiovascular. El tejido adiposo visceral juega un papel fundamental en este proceso, dado que secreta una variedad de sustancias biológicamente activas denominadas adipoquinas o adipocitoquinas, tales como leptina, resistina, adiponectina, factor de necrosis tumoral alfa (TNFa), y visfatina entre otras. La visfatina es una citoquina descubierta recientemente y su rol en la enfermedad cardiovascular es controversial y aún no ha sido completamente dilucidado. Estudios realizados en humanos y en modelos experimentales en animales sugieren que la visfatina tendría un papel muy importante en las patologías asociadas a la enfermedad cardiovascular. Esta revisión intenta mostrar los últimos avances sobre el rol de la visfatina y las principales adipocitoquinas en las patologías cardiovasculares y el síndrome metabólico.Cardiovascular disease is the leading cause of mortality in western countries. Metabolic syndrome (MS), characterized by hyperlipidemia, hypertension, obesity and hyperglycemia, is a significant risk factor for cardiovascular disease. Visceral adipose tissue play a key role in the development of metabolic syndrome since this tissue secrets a variety of bioactive substances named adipokines or adipocytokines such as leptin, resistin, adiponectin, tumor necrosis factor alfa (TNFa), and visfatin. Visfatin has been described recently and its role in cardiovascular disease is controversial and has not yet been fully elucidated. Studies in human and animal experimental models suggest that visfatin would have a key role in the pathologies associates with cardiovascular disease. This review is focused in the role of visfatin as well as the main dipocytokines with cardiovascular disease and metabolic syndrome.Fil: Rodríguez Lanzi, María Cecilia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Área de Fisiología PatológicaFil: Miatello, Roberto. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Área de Fisiología PatológicaFil: Vazquez-Prieto, Marcela Alejandra. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Área de Fisiología Patológic

Caracterización y cuantificación de células progenitoras endoteliales de ratas espontáneamente hipertensas alimentadas con fructosa

Objetivo: Examinar cómo se ve afecta la participación de las células progenitoras endoteliales (CPE) por la resistencia a la insulina (IR) asociada a un modelo experimental de síndrome metabólico (SM), generado por la administración crónica de fructosa a ratas espontáneamente hipertensas. Material y métodos: Ratas WKY y SHR, macho, distribuidas en 4 grupos (n=8 c/u): WKY: controles; FFR: WKY recibiendo fructosa en agua de bebida al 10 % (v/v) durante 6 semanas; SHR; FFHR: SHR recibiendo fructosa en agua de bebida al 10 % (v/v) durante 6 semanas. Al finalizar el protocolo se determinó: presión arterial sistólica, variables bioquímicas, índice HOMA, cuantificación por citometría de flujo de los niveles de CPE en sangre periférica y en médula ósea, inmunofluorescencia en cultivo celular, para identificar los marcadores CD34 y VEGFR-2, recuento de colonias de CPE y actividad de NAD(P)H-oxidasa en tejido aórtico. Resultados: Se confirmó el modelo experimental en base a las variables metabólicas analizadas. Se observó una disminución en los niveles de CPE; en sangre periférica y médula ósea, la que se hace más importante en los grupos de animales tratados con fructosa. En estos también hay menor número de colonias de CPE desarrolladas en cultivo celular y presentan un aumento en los niveles de estrés oxidativo, estimado por la actividad de NAD(P)H oxidasa. Conclusión: el SM causado por la administración crónica de fructosa en FFHR ha demostrado generar una disminución en los niveles de CPE, así como en su capacidad funcional. Los mecanismos intracelulares que producen este fenómeno podrían estar desencadenados por el grado de IR que presenta este modelo experimental.Objective: To examine alterations in participation of endothelial progenitor cells (EPC) because of insulin resistance (IR) associated with an experimental model of metabolic syndrome (MS) generated by chronic administration of fructose to spontaneously hypertensive rats (SHR) Material and methods: WKY and SHR rats, male, were distributed into 4 groups (n = 8 c/u): WKY: control; FFR: WKY receiving fructose in drinking water to 10% (v/v) for 6 weeks , SHR; FFHR: SHR receiving fructose in drinking water to 10% (v/v) for 6 weeks. At the end of the protocol the following variables were determined: systolic blood pressure, biochemical variables, HOMA index, levels of EPC quantified by flow cytometry in peripheral blood and bone marrow, immunofluorescence in cell culture to identify markers CD34 and VEGFR-2, EPC colony count and NAD(P)H-oxidase activity in aortic tissue. Results: We confirmed the experimental model based on metabolic variables analyzed. A decrease in the levels of CPE, in peripheral blood and bone marrow, which becomes more important groups of animals treated with fructose was observed .In these groups there are also fewer colonies of developed EPC in cell culture and exhibit an increased levels of oxidative stress, estimated by the activity of NAD(P)H-oxidase. Conclusion: the SM caused by chronic administration of fructose in FFHR has proven to generate a decrease in the levels of CPE, as well as its functional capacity. The intracellular mechanisms that produce this phenomenon could be triggered by the degree of IR presented in this experimental model.Fil: Lembo, Carina. Universidad Nacional de Cuyo. Facultad de Ciencias MédicasFil: Renna, Nicolás Federico. Universidad Nacional de Cuyo. Facultad de Ciencias MédicasFil: Diez, Emiliano Raúl. Universidad Nacional de Cuyo. Facultad de Ciencias MédicasFil: Vazquez-Prieto, Marcela Alejandra. Universidad Nacional de Cuyo. Facultad de Ciencias MédicasFil: Miatello, Roberto. Universidad Nacional de Cuyo. Facultad de Ciencias Médica

Garlic and Onion Attenuates Vascular Inflammation and Oxidative Stress in Fructose-Fed Rats

This study evaluates the antioxidant and the anti-inflammatory properties of garlic (G) and onion (O) in fructose-fed rats (FFR). Thirty-day-old male Wistar rats were assigned to control (C), F (10% fructose in drinking water), F+T (tempol 1 mM as control antioxidant), F+G, and F+O. Aqueous G and O extracts were administered orally in doses of 150 and 400 mg/kg/d respectively, and along with tempol, were given during the last 8 weeks of a 14-week period. At the end of the study, FFR had developed insulin resistance, aortic NADPH oxidase activity, increased SBP, plasma TBARS and vascular cell adhesion molecule-1 (VCAM-1) expression in mesenteric arteries, and a decrease in heart endothelial nitric oxide synthase (eNOS). Garlic and onion administration to F rats reduced oxidative stress, increased eNOS activity, and also attenuated VCAM-1 expression. These results provide new evidence showing the anti-inflammatory and antioxidant effect of these vegetables

Catechin and quercetin attenuate adipose inflammation in fructose‐fed rats and 3T3‐L1 adipocytes

Scope This study evaluated the capacity of dietary catechin (C), quercetin (Q), and the combination of both (CQ), to attenuate adipose inflammation triggered by high fructose (HFr) consumption in rats and by tumor necrosis factor alpha (TNF‐α) in 3T3‐L1 adipocytes. Methods and results In rats, HFr consumption for 6 wk caused dyslipidemia, insulin resistance, reduced plasma adiponectin, adiposity, and adipose tissue inflammation. Dietary supplementation with 20 mg/kg/day of C, Q, and CQ improved all these parameters. In 3T3‐L1 adipocytes, C and Q attenuated TNF‐α‐induced elevated protein carbonyls, increased proinflammatory cytokine expression (MCP‐1, resistin), and decreased adiponectin. The protective effects of C and Q on adipose inflammation are in part associated with their capacity to (i) decrease the activation of the mitogen‐activated kinases (MAPKs) JNK and p38; and (ii) prevent the downregulation of PPAR‐γ. In summary, C and Q, and to a larger extent the combination of both, attenuated adipose proinflammatory signaling cascades and regulated the balance of molecules that improve (adiponectin) or impair (TNF‐α, MCP‐1, resistin) insulin sensitivity. Conclusion Together, these findings suggest that dietary Q and C may have potential benefits in mitigating MetS‐associated adipose inflammation, oxidative stress, and insulin resistance.EEA La ConsultaFil: Vazquez Prieto, Marcela Alejandra. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Area de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico- Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Bettaieb, Ahmed. University of California. Department of Nutrition; Estados UnidosFil: Rodriguez Lanzi, Cecilia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Area de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico- Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Soto Vargas, Verónica Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Perdicaro, Diahann Jeanette. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Area de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico- Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Galmarini, Claudio Romulo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria La Consulta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; ArgentinaFil: Haj, Fawaz G. University of California. Department of Nutrition; Estados Unidos. University of California. Department of Internal Medicine; Estados UnidosFil: Miatello, Roberto Miguel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Area de Fisiología Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico- Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Oteiza, Patricia I. University of California. Department of Nutrition; Estados Unidos. University of California. Department of Environmental Toxicology; Estados Unido

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2-6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates