1,721,021 research outputs found
Type 1 diabetes mellitus as a polygenic multifactorial disease: immunopathogenic mechanisms of beta-cell destruction.
No full textPathological changes in human islets
No full textPurpose of review: This paper reviews the most recent articles on human islet inflammation in type 1 and type 2 diabetes, in recurrent autoimmunity and alloimmunity, which can result in pancreatic graft failure. Finally, we examine data supporting the hypothesis that islet destruction is accompanied by regenerative phenomena aimed at restoring beta cell mass. Recent findings: Type 1 diabetes: Application of high-resolution magnetic resonance imaging and fluorescence of long circulating nanoparticles was successfully used in evaluating islet inflammation in animal models of autoimmune diabetes. Among environmental factors in type 1 diabetes, enteroviral beta-cell infection was reported in some Finnish type 1 diabetic patients. Finally, a family of modulators of cytokine signaling was reported to occur in human islets. Pancreatic islet transplantation: Several observations suggested that (a) interventions to activate, amplify, or sustain intra-islet endothelial cells may facilitate islet revascularization; and (b) the development of strategies aimed at preventing upregulation of proinflammatory molecules can improve islet transplantation. Type 2 diabetes: Multiple factors such as proinflammatory cytokines, high glucose and free fatty acids can contribute to islet inflammation in type 2 diabetes. Accordingly, type 2 diabetic islets show increased apoptotic phenomena and a series of functional defects. Beta-cell regeneration: A number of reports observed beta-cell neogenesis in rodent and in human pancreas. Newly formed beta-cells likely derive either from ductal cells or as results of proliferation phenomena from pre-existing beta cells. Summary: Increasing evidence supports the hypothesis that islet inflammation together with beta-cell dysfunction is a common feature to both type 1 and type 2 diabetes
Combination therapy with metformin plus vildagliptin in type 2 diabetes mellitus
No full textINTRODUCTION: Type 2 diabetes mellitus (T2DM) is pathophysiologically characterized by a combination of insulin resistance and beta-cell dysfunction. Consequently, a proper treatment of such a disease should target both of these defects. Dipeptidyl peptidase-4 (DPP-4) inhibitors are among the most recent additions to the therapeutic options for T2DM and are able to increase circulating levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thus stimulating glucose-dependent insulin secretion. AREAS COVERED: This paper provides an overview of the clinical results of combination therapy with metformin and the DPP-4 inhibitor vildagliptin in T2DM patients. EXPERT OPINION: Vildagliptin-metformin single-tablet combination is indicated for the treatment of T2DM patients not achieving a sufficient glycemic control at their maximally tolerated dose of metformin. Results from clinical trials provide evidence of vildagliptin efficacy administered in addition to metformin, as either first- or second-line treatment. The vildagliptin-metformin association seems to have favorable effects on beta-cell function and is characterized by good safety and tolerability profiles when compared with other antidiabetic agents. Of note, data available suggest that administration of fixed-dose combination products, together with the low incidence of adverse gastrointestinal events, may improve compliance and adherence of patients to therapy, resulting in an improved metabolic control
Can NK cells be a therapeutic target in human type 1 diabetes?
No full textType 1 diabetes is caused by the autoimmune destruction of insulin-producing cells with consequent hyperglycemia and serious chronic complications. Both innate and adaptive immune responses participate in disease pathogenesis. Studies in animal models and in man have shown that NK cells are involved both in disease progression and in disease protection, thus suggesting that NK cells can represent a potential therapeutic target in type 1 diabetes, once the contribution of these cells to islet autoimmunity has been fully elucidated
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
MicroRNA profiling in sera of patients with type 2 diabetes mellitus reveals an upregulation of miR-31 expression in subjects with microvascular complications
Full text linkType 2 diabetes (T2D) is a metabolic disease characterized by chronic hyperglycaemia due to a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. Chronic hyperglycemia is associated with long-term micro- and macrovascular complications leading to dysfunction of several organs including kidney, heart, eye and nervous system. Early identification of chronic diabetic complications is necessary in order to prevent dysfunction and failure of these different organs. MicroRNAs (or miRNAs) are small endogenous RNAs, which negatively regulate gene expression. Recently, it has been demonstrated that miRNAs can be secreted by cells, thus being detectable in serum and in other biological fluids. Circulating microRNAs have been proposed as possible biomarkers of several diseases. Here, we performed a miRNAs expression profiling in the sera of T2D patients with or without vascular complications in order to find specific biomarkers to characterize T2D complications. We analyzed the expression of 384 microRNAs in serum pools from 3 groups of T2D patients: 12 T2D patients without any chronic complications, 12 T2D patients with macrovascular complications and 12 with microvascular complications. We found 223 miRNAs expressed in T2D,224 inT2D with microvascular and221 inT2D with macrovascular complications. Among expressed microRNAs, 45 resulted upregulated and 23 downregulated in microvascular patients sera, while 13 upregulated and 41 downregulated in macrovascular T2D patients compared to those without complications. We focused and validated microRNA miR-31 expression in single sera from each group, which resulted significantly upregulated in patients with microvascular complications and may be indeed related to the presence of microangiopathy. In conclusion, our study has identified miR-31 as a promising biomarker for diabetic microvascular complications; further prospective studies in the clinical setting are however required to establish the real utility of measuring serum circulating levels of this microRNA
Effetto del naloxone e del naltrexone sulla spesa energetica post-prandiale e sulla risposta del pancreas endocrino ad un pasto misto nell'obesita essenziale. [Effect of naloxone and naltrexone on the postprandial energy expenditure and endocrine pancreas response to a mixed meal in essential obesity]
No full textIt has been recently shown that the opioid antagonists naloxone and naltrexone are able to reduce appetite and to raise energy expenditure in animal models. The results of studies in humans are inconclusive. In 10 female obese patients we have evaluated the effects of naloxone infusion (2 mg/2 h) on energy expenditure, measured by indirect calorimetry (Deltatrac) and on plasmatic levels of glucose, insulin, glucagon and somatostatin, fasting and after the assumption of a standard 567 kcal meal (C = 20%, P = 20%, L = 60%). We have repeated the tests after a dietary period of 1 month, associated with naltrexone assumption. Acute administration of naloxone caused similar effects at the beginning and at the end of the study; we have observed a raise of caloric expenditure, a decrease of hyperinsulinemia and a high response of somatostatin to metabolic stimulus. After therapy, even with a weight reduction of 6%, we haven't observed either variations of energy expenditure or hormonal level changes. We conclude that in obese women opioid hypertone plays a role in thermic effect of meals and in the impaired response to the nutrients of the gastroenteropancreatic axis. The absence of any effects of naltrexone on the variables that we have studied is perhaps due to the difference in the dose, way of administration and of the different action on the target receptor by the two opioid antagonists
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