155 research outputs found

    Macro- and Microvascular Function in Middle-Aged Individuals with Low Cardiovascular Disease Risk

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    Aims: To investigate the microvascular function in apparently healthy individuals showing signs of early macrovascular endothelial dysfunction. Methods: Healthy participants aged between 30–55 years were recruited for the present study. Baseline measurements included body-mass index (BMI), waist-to-hip ratio (WHR), 24-h blood pressure, as well as fasted venous glucose, triglycerides (TG) and cholesterol (HDL, LDL and total). Brachial artery reactivity was measured using the flow-mediated dilation (FMD) technique and retinal vessel reactivity was assessed by using the Dynamic Retinal Vessel Analyser (DVA) in all individuals. The enrolled participants were separated in two groups, based on either a reduced (group 1

    Canadian Jewish Poetry: A Roundtable

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    Is Canadian Jewish Poetry a meaningful category of study? Are there particular traits that differentiate Canadian Jewish poets from poets of other countries, or from writers in other genres? How do contemporary poets confront the looming legacy of Irving Layton, Leonard Cohen, and A.M. Klein? Six prominent poets and scholars conduct a roundtable discussion to articulate recent developments in the field.La poĂ©sie juive canadienne est-elle une catĂ©gorie d’étude significative? Y a-t-il des traits particuliers qui diffĂ©rencient les poĂštes juifs canadiens des poĂštes d’autres pays, ou des Ă©crivains d’autres genres? Comment les poĂštes contemporains font-ils face Ă  l’hĂ©ritage imminent d’Irving Layton, Leonard Cohen et A.M. Klein ? Six poĂštes et universitaires Ă©minents organisent une table ronde pour exposer les dĂ©veloppements rĂ©cents dans ce domaine

    CLH-3, a ClC-2 anion channel ortholog activated during meiotic maturation in C. elegans oocytes

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    AbstractBackground: ClC anion channels are ubiquitous and have been identified in organisms as diverse as bacteria and humans. Despite their widespread expression and likely physiological importance, the function and regulation of most ClCs are obscure. The nematode Caenorhabditis elegans offers significant experimental advantages for defining ClC biology. These advantages include a fully sequenced genome, cellular and molecular manipulability, and genetic tractability.Results: We show by patch clamp electrophysiology that C. elegans oocytes express a hyperpolarization- and swelling-activated Cl− current with biophysical characteristics strongly resembling those of mammalian ClC-2. Double-stranded RNA–mediated gene interference (RNAi) and single-oocyte RT-PCR demonstrated that the channel is encoded by clh-3, one of six C. elegans ClC genes. CLH-3 is inactive in immature oocytes but can be triggered by cell swelling. However, CLH-3 plays no apparent role in oocyte volume homeostasis. The physiological signal for channel activation is the induction of oocyte meiotic maturation. During meiotic maturation, the contractile activity of gonadal sheath cells, which surround oocytes and are coupled to them via gap junctions, increases dramatically. These ovulatory sheath cell contractions are initiated prematurely in animals in which CLH-3 expression is disrupted by RNAi.Conclusions: The inwardly rectifying Cl− current in C. elegans oocytes is due to the activity of a ClC channel encoded by clh-3. Functional and structural similarities suggest that CLH-3 and mammalian ClC-2 are orthologs. CLH-3 is activated during oocyte meiotic maturation and functions in part to modulate ovulatory contractions of gap junction–coupled gonadal sheath cells

    Effects of Bariatric Surgery on Human Small Artery Function Evidence for Reduction in Perivascular Adipocyte Inflammation, and the Restoration of Normal Anticontractile Activity Despite Persistent Obesity

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    ObjectivesThe aim of this study was to investigate the effects of bariatric surgery on small artery function and the mechanisms underlying this.BackgroundIn lean healthy humans, perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arteries, but this is lost in obesity-associated conditions such as the metabolic syndrome and type II diabetes where there is evidence of adipocyte inflammation and increased oxidative stress.MethodsSegments of small subcutaneous artery and perivascular fat were harvested from severely obese individuals before (n = 20) and 6 months after bariatric surgery (n = 15). Small artery contractile function was examined in vitro with wire myography, and perivascular adipose tissue (PVAT) morphology was assessed with immunohistochemistry.ResultsThe anticontractile activity of PVAT was lost in obese patients before surgery when compared with healthy volunteers and was restored 6 months after bariatric surgery. In vitro protocols with superoxide dismutase and catalase rescued PVAT anticontractile function in tissue from obese individuals before surgery. The improvement in anticontractile function after surgery was accompanied by improvements in insulin sensitivity, serum glycemic indexes, inflammatory cytokines, adipokine profile, and systolic blood pressure together with increased PVAT adiponectin and nitric oxide bioavailability and reduced macrophage infiltration and inflammation. These changes were observed despite the patients remaining severely obese.ConclusionsBariatric surgery and its attendant improvements in weight, blood pressure, inflammation, and metabolism collectively reverse the obesity-induced alteration to PVAT anticontractile function. This reversal is attributable to reductions in local adipose inflammation and oxidative stress with improved adiponectin and nitric oxide bioavailability

    Abnormal Remodeling of Subcutaneous Small Arteries Is Associated With Early Diastolic Impairment in Metabolic Syndrome

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    Background Small artery pathophysiology is frequently invoked as a cause of obesity‐related diastolic heart failure. However, evidence to support this hypothesis is scant, particularly in humans. Methods and Results To address this, we studied human small artery structure and function in obesity and looked for correlations between vascular parameters and diastolic function. Seventeen obese patients with metabolic syndrome and 5 control participants underwent echocardiography and subcutaneous gluteal fat biopsy. Small arteries were isolated from the biopsy and pressure myography was used to study endothelial function and wall structure. In comparison with the control group, small arteries from obese participants exhibited significant endothelial dysfunction, assessed as the vasodilatory response to acetylcholine and also pathological growth of the wall. For the obese participants, multiple regression analysis revealed an association between left atrial volume and both the small artery wall thickness (ÎČ=0.718, P =0.02) and wall‐to‐lumen ratio (ÎČ=0.605, P =0.02). Furthermore, the E:Eâ€Č ratio was associated with wall‐to‐lumen ratio (ÎČ=0.596, P =0.02) and inversely associated with interleukin‐6 (ÎČ=−0.868, P =0.03). By contrast, endothelial function did not correlate with any of the echocardiographic parameters studied. Conclusions Although the small arteries studied were not cardiac in origin, our results support a role for small artery remodeling in the development of diastolic dysfunction in humans. Further direct examination of the structure and function of the myocardial resistance vasculature is now warranted, to elucidate the temporal association between metabolic risk factors, small artery injury, and diastolic impairment. </jats:sec
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