375 research outputs found

    Pancreatic alpha cell mass in European subjects with type 2 diabetes

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    AIMS/HYPOTHESIS: Type 2 diabetes is a bi-hormonal disease characterised by relative hypoinsulinaemia and hyperglucagonaemia with elevated blood glucose levels. Besides pancreatic beta cell defects, a low number of beta cells (low beta cell mass) may contribute to the insufficient secretion of insulin. In this study our aim was to determine whether the alpha cell mass is also altered. METHODS: Using a point counting method, we measured the ratio of alpha to beta cell areas in pancreas samples obtained at autopsy from 50 type 2 diabetic subjects, whose beta cell mass had previously been found to be 36% lower than that of 52 non-diabetic subjects. RESULTS: The topography of alpha and beta cells was similar in both groups: many alpha cells were localised in the centre of the islets and the ratio of alpha/beta cell areas increased with islet size. The average ratio was significantly higher in type 2 diabetic subjects (0.72) than in non-diabetic subjects (0.42), with, however, a large overlap between the two groups. In contrast, the alpha cell mass was virtually identical in type 2 diabetic subjects (366 mg) and non-diabetic subjects (342 mg), and was not influenced by sex, BMI or type of diabetes treatment. CONCLUSIONS: The higher proportion of alpha to beta cells in the islets of some type 2 diabetic subjects is due to a decrease in beta cell number rather than an increase in alpha cell number. This imbalance may contribute to alterations in the normal inhibitory influence exerted by beta cells on alpha cells, and lead to the relative hyperglucagonaemia observed in type 2 diabete

    Calorimetric study of geopolymer binders based on natural pozzolan

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    This paper investigates the kinetics of geopolymerisation in an inorganic polymeric binder based on a natural pozzolan. The heat released by the exothermic geopolymerisation reaction process is monitored under isothermal temperature conditions, maintained in a differential scanning calorimeter using a water circulation cell. Calorimetric data are obtained isothermally at 65, 75, and 85 °C with various Na2O/Al2O3 and SiO2/Na2O molar ratios and in the presence and absence of small amounts of calcium aluminate cement (used as an efflorescence control admixture in these binder systems). The first stage of reaction, which is rapid and strongly exothermic, is shortened as the temperature increases. The total heat of reaction increases in the mixes containing calcium aluminate cement, but the apparent activation energy calculated using a pseudo-first-order reaction model is lower than without added calcium aluminate cement. At a constant overall SiO2/Na2O molar ratio, the apparent activation energy is decreased as the Na2O/Al2O3 molar ratio increases. Calcium aluminate cement, therefore, reduces the minimum energy required to initiate geopolymerisation reactions of this natural pozzolan and facilitates the progress of the reactions which lead to formation of a cementitious product

    An australian audit of vaccination status in children and adolescents with inflammatory bowel disease

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    <p>Abstract</p> <p>Background</p> <p>Children and adolescents with inflammatory bowel disease (IBD) are at increased risk of vaccine preventable diseases (VPD). This includes invasive pneumococcal disease and influenza. The primary aim of this study was to describe compliance with current Australian guidelines for vaccination of children and adolescents diagnosed with IBD. A secondary aim was to review the serological screening for VPD.</p> <p>Methods</p> <p>A random sample of patients (0-18 years at diagnosis), were selected from the Victoria Australia state based Pediatric Inflammatory Bowel Disease Register. A multi-faceted retrospective review of immunization status was undertaken, with hospital records audited, a telephone interview survey conducted with consenting parents and the vaccination history was checked against the primary care physician and Australian Childhood Immunization Register (ACIR) records. The routine primary childhood vaccinations and administration of the recommended additional influenza and pneumococcal vaccines was clarified.</p> <p>Results</p> <p>This 2007 audit reviewed the immunization status of 101individuals on the Victorian Pediatric IBD database. Median age at diagnosis was 12.1 years, 50% were on active immunosuppressive therapy. 90% (38/42) [95% confidence intervals (CI) 77%; 97%] with complete immunization information were up-to-date with routine primary immunizations. Only 5% (5/101) [95% CI 2%; 11%] received a recommended pneumococcal vaccine booster and 10% (10/101) [95% CI 5%; 17%] had evidence of having ever received a seasonal influenza vaccine. Those living in rural Victoria (p = 0.005) and younger at the age of diagnosis (p = 0.002) were more likely to have ever received an influenza vaccine Serological testing, reviewing historical protection from VPD, identified 18% (17/94) with evidence of at least one serology sample.</p> <p>Conclusion</p> <p>This study highlights poor compliance in IBD patients for additional recommended vaccines. A multi-faceted approach is required to maximize protection from VPD in this vulnerable special risk population.</p

    HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth

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    The reduced diameter of skeletal myofibres is a hallmark of several congenital myopathies, yet the underlying cellular and molecular mechanisms remain elusive. In this study, we investigate the role of HACD1/PTPLA, which is involved in the elongation of the very long chain fatty acids, in muscle fibre formation. In humans and dogs, HACD1 deficiency leads to a congenital myopathy with fibre size disproportion associated with a generalized muscle weakness. Through analysis of HACD1-deficient Labradors, Hacd1-knockout mice, and Hacd1-deficient myoblasts, we provide evidence that HACD1 promotes myoblast fusion during muscle development and regeneration. We further demonstrate that in normal differentiating myoblasts, expression of the catalytically active HACD1 isoform, which is encoded by a muscle-enriched splice variant, yields decreased lysophosphatidylcholine content, a potent inhibitor of myoblast fusion, and increased concentrations of ≄C18 and monounsaturated fatty acids of phospholipids. These lipid modifications correlate with a reduction in plasma membrane rigidity. In conclusion, we propose that fusion impairment constitutes a novel, non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism

    Quantitative analysis of cell composition and purity of human pancreatic islet preparations

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    Author Manuscript 2011 May 1.Despite improvements in outcomes for human islet transplantation, characterization of islet preparations remains poorly defined. This study used both light microscopy (LM) and electron microscopy (EM) to characterize 33 islet preparations used for clinical transplants. EM allowed an accurate identification and quantification of cell types with measured cell number fractions (mean±s.e.m.) of 35.6±2.1% ÎČ-cells, 12.6±1.0% non-ÎČ-islet cells (48.3±2.6% total islet cells), 22.7±1.5% duct cells, and 25.3±1.8% acinar cells. Of the islet cells, 73.6±1.7% were ÎČ-cells. For comparison with the literature, estimates of cell number fraction, cell volume, and extracellular volume were combined to convert number fraction data to volume fractions applicable to cells, islets, and the entire preparation. The mathematical framework for this conversion was developed. By volume, ÎČ-cells were 86.5±1.1% of the total islet cell volume and 61.2±0.8% of intact islets (including the extracellular volume), which is similar to that of islets in the pancreas. Our estimates produced 1560±20 cells in an islet equivalent (volume of 150-ÎŒm diameter sphere), of which 1140±15 were ÎČ-cells. To test whether LM analysis of the same tissue samples could provide reasonable estimates of purity of the islet preparations, volume fraction of the islet tissue was measured on thin sections available from 27 of the clinical preparations by point counting morphometrics. Islet purity (islet volume fraction) of individual preparations determined by LM and EM analyses correlated linearly with excellent agreement (R[superscript 2]=0.95). However, islet purity by conventional dithizone staining was substantially higher with a 20–30% overestimation. Thus, both EM and LM provide accurate methods to determine the cell composition of human islet preparations and can help us understand many of the discrepancies of islet composition in the literature.National Institutes of Health (U.S.) (Grant RO1-DK063108)National Institutes of Health (U.S.) (Grant NCRR ICR U4Z RR 16606)Joslin Diabetes and Endocrinology Research Center (Grant DK36836)Diabetes Research & Wellness FoundationJuvenile Diabetes Research Foundation International (Islet Transplantation, Harvard Medical School

    An investigation of the mechanisms for strength gain or loss of geopolymer mortar after exposure to elevated temperature

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    When fly ash-based geopolymer mortars were exposed to a temperature of 800 °C, it was found that the strength after the exposure sometimes decreased, but at other times increased. This paper shows that ductility of the mortars has a major correlation to this strength gain/loss behaviour. Specimens prepared with two different fly ashes, with strengths ranging from 5 to 60 MPa, were investigated. Results indicate that the strength losses decrease with increasing ductility, with even strength gains at high levels of ductility. This correlation is attributed to the fact that mortars with high ductility have high capacity to accommodate thermal incompatibilities. It is believed that the two opposing processes occur in mortars: (1) further geopolymerisation and/or sintering at elevated temperatures leading to strength gain; (2) the damage to the mortar because of thermal incompatibility arising from non-uniform temperature distribution. The strength gain or loss occurs depending on the dominant process

    Postnatal Development of Numbers and Mean Sizes of Pancreatic Islets and Beta-Cells in Healthy Mice and GIPRdn Transgenic Diabetic Mice

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    The aim of this study was to examine postnatal islet and beta-cell expansion in healthy female control mice and its disturbances in diabetic GIPRdn transgenic mice, which exhibit an early reduction of beta-cell mass. Pancreata of female control and GIPRdn transgenic mice, aged 10, 45, 90 and 180 days were examined, using state-of-the-art quantitative-stereological methods. Total islet and beta-cell volumes, as well as their absolute numbers increased significantly until 90 days in control mice, and remained stable thereafter. The mean islet volumes of controls also increased slightly but significantly between 10 and 45 days of age, and then remained stable until 180 days. The total volume of isolated beta-cells, an indicator of islet neogenesis, and the number of proliferating (BrdU-positive) islet cells were highest in 10-day-old controls and declined significantly between 10 and 45 days. In GIPRdn transgenic mice, the numbers of islets and beta-cells were significantly reduced from 10 days of age onwards vs. controls, and no postnatal expansion of total islet and beta-cell volumes occurred due to a reduction in islet neogenesis whereas early islet-cell proliferation and apoptosis were unchanged as compared to control mice. Insulin secretion in response to pharmacological doses of GIP was preserved in GIPRdn transgenic mice, and serum insulin to pancreatic insulin content in response to GLP-1 and arginine was significantly higher in GIPRdn transgenic mice vs. controls. We could show that the increase in islet number is mainly responsible for expansion of islet and beta-cell mass in healthy control mice. GIPRdn transgenic mice show a disturbed expansion of the endocrine pancreas, due to perturbed islet neogenesis
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