Pancreatic alpha cell mass in European subjects with type 2 diabetes

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

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

Meta-halloysite to improve compactness in iron-rich laterite-based alkali activated materials

In this paper, the results of the experimental investigation were used to understand the effect of fine meta-halloysite on the reactivity, mechanical and microstructural properties of laterite-based geopolymers. Laterite was replaced by 0, 20, 30 and 50 wt% of meta-halloysite in order to improve the physico-chemical performance. Meta-halloysite was prepared by calcination of natural halloysite at 600 °C. The moduli (molar ratio SiO2/Na2O) of the activating solutions were 1.04, 0.92, and 0.75 with H2O/Na2O = 9.78, 10.45 and 12.04, respectively. The results indicated that calcined laterite has a high specific surface area (43.00 ± 0.12 m2/g), notwithstanding a high average particle size (d50 = 45.20 μm) compared to meta-halloysite with a smaller average particle size (d50 = 8.40 μm) and a specific surface (29.80 ± 0.16 m2/g). The compressive strength of geopolymers increased upon the addition of meta-halloysite from 12 MPa to 45 MPa at 28 days. While the setting time and water absorption decrease with increase in the of meta-halloysite content as well as with increase in Si/Al, Si/Fe, Al/Fe and Na/Al molar ratios used in the synthesis of geopolymers. The use of fine meta-halloysite resulted in better efficiency and improved mechanical performance of synthesized products

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

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% β-cells, 12.6±1.0% non-β-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 β-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, β-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-μm diameter sphere), of which 1140±15 were β-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

I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

Background and aims: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.. Methods: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment. Results: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.. Conclusions: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients

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

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

HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Background & aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764). Expression levels of HLA-DP on intestinal epithelial cells (IECs) in individuals with and without UC were quantified. Human intestinal 3-dimensional (3D) organoid cocultures with human NK cells were used to determine functional consequences of interactions between HLA-DP and NKp44.Results: These studies identified HLA-DPA1∗01:03-DPB1∗04:01 (HLA-DP401) as a risk haplotype and HLA-DPA1∗01:03-DPB1∗03:01 (HLA-DP301) as a protective haplotype for UC in European populations. HLA-DP expression was significantly higher on IECs of individuals with UC compared with controls. IECs in human intestinal 3D organoids derived from HLA-DP401pos individuals showed significantly stronger binding of NKp44 compared with HLA-DP301pos IECs. HLA-DP401pos IECs in organoids triggered increased degranulation and tumor necrosis factor production by NKp44+ NK cells in cocultures, resulting in enhanced epithelial cell death compared with HLA-DP301pos organoids. Blocking of HLA-DP401-NKp44 interactions (anti-NKp44) abrogated NK cell activity in cocultures.Conclusions: We identified an UC risk HLA-DP haplotype that engages NKp44 and activates NKp44+ NK cells, mediating damage to intestinal epithelial cells in an HLA-DP haplotype-dependent manner. The molecular interaction between NKp44 and HLA-DP401 in UC can be targeted by therapeutic interventions to reduce NKp44+ NK cell-mediated destruction of the intestinal epithelium in UC

In vitro Anticancer Screening of 24 Locally Used Nigerian Medicinal Plants

Background: Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity. Methods: The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines. Results: Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma cell lines. Erythrophleum suaveolens (Guill. & Perr.) Brenan was found to demonstrate potent anti-cancer activity in this study exhibiting IC50 = 0.2-1.3 $\mu$g/ml. Conclusions: Based on the significantly potent activity of some plants extracts reported here, further studies aimed at mechanism elucidation and bio-guided isolation of active anticancer compounds is currently underway.Chemistry and Chemical Biolog