Abbreviations eGFP Enhanced green fluorescent protein GSIS Glucose-stimulated insulin secretion HG High glucose (15 mmol/l) LG Low glucose (3 mmol/l) NICCs Neonatal islet-like cell clusters NSG NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NOD-scid Il2rγ null ; mice) Dr Y. Ivashchenko, who made important contributions to this research, died in December 2016 before publication of this work.
SummaryMeasurement of endothelial function in patients with atherosclerosis and lipid disorders is an important tool for the risk evaluation of a cardiovascular event, such as acute myocardial infarction and stroke. The feasibility of measuring endothelial function non-invasively in animal models has been limited so far. Therefore, we compared the assessment of endothelial function by in vivo transcutaneous vascular ultrasound (TVU) with the classical method of ex vivo organ bath, using the carotid artery of hypercholesterolaemic and normocholesterolaemic rabbits. The assessments of endothelial function by both techniques were performed on the same segments of the carotid artery. Vascular ultrasound detected impaired endothelium-dependent vasorelaxation induced by acetylcholine in the common carotid artery of hypercholesterolaemic rabbits. These results strongly correlated with measurements of endothelial function of isolated carotid artery rings. Furthermore, atherogenic diet caused significant fatty streak formation in the aorta, as well as significant increase of C-reactive protein and cholesterol levels. Endothelial function, an early marker of cardiovascular risk, could be non-invasively assessed and graded by TVU measurements. It correlated highly with vasoreactivity of isolated vessels in an organ bath (r 2 ¼ 0.68). We conclude that vascular ultrasound in hypercholesterolaemic rabbits is a valid method for evaluating endothelial function associated with atherosclerosis.
ObjectiveGlucagon-like peptide-1 induces glucose-dependent insulin secretion and, in rodents, increases proliferation and survival of pancreatic beta cells. To investigate the effects on human beta cells, we used immunodeficient mice transplanted with human islets. The goal was to determine whether lixisenatide, a glucagon-like peptide-1 receptor agonist, improves human islet function and survival in vivo.MethodsFive independent transplant studies were conducted with human islets from five individual donors. Diabetic human islet-engrafted immunodeficient mice were treated with lixisenatide (50, 150, and 500 µg/kg) or vehicle. Islet function was determined by blood glucose, plasma human insulin/C-peptide, and glucose tolerance tests. Grafts were analyzed for total beta- and alpha-cell number, percent proliferation, and levels of apoptosis.ResultsDiabetic mice transplanted with marginal human islet mass and treated with lixisenatide were restored to euglycemia more rapidly than vehicle-treated mice. Glucose tolerance tests, human plasma insulin, and glucose-stimulation indices of lixisenatide-treated mice were significantly improved compared to vehicle-treated mice. The percentages of proliferating or apoptotic beta cells at graft recovery were not different between lixisenatide-treated and vehicle-treated mice. Nevertheless, in one experiment we found a significant twofold to threefold increase in human beta-cell numbers in lixisenatide-treated compared to vehicle-treated mice.ConclusionDiabetic human islet-engrafted immunodeficient mice treated with lixisenatide show improved restoration of normoglycemia, human plasma insulin, and glucose tolerance compared to vehicle-treated mice engrafted with the same donor islets. Because the proliferative capacity of human beta cells is limited, improved beta-cell survival coupled with enhanced beta-cell function following lixisenatide treatment may provide the greatest benefit for diabetic patients with reduced functional islet mass.
In vitro, la trypsine associée au glycérol a mené à une désactivation de virus courants du rhume. Une étude pilote et une étude comparative multicentrique ont évalué la réduction de la charge virale in vivo et l'amélioration de la qualité de vie après l'utilisation des substances actives sous forme de spray buccal chez des sujets atteints d'un rhume courant. Les résultats ont montré une diminution de la charge virale et de la durée du rhume ainsi qu'une amélioration de la qualité de vie.
La tripsina di merluzzo in combinazione con il glicerolo si è dimostrata in grado di disattivare i virus del raffreddore comune in vitro. Uno studio pilota e uno studio multicentrico comparativo hanno esaminato la riduzione della carica virale in vivo e il miglioramento della qualità della vita a seguito dell'uso di questi principi attivi sotto forma di uno spray per la gola da parte di soggetti con raffreddore comune. I risultati hanno evidenziato una riduzione della carica virale e della durata del raffreddore, come pure un miglioramento della qualità della vita.
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