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Transplantation of islet cells is an effective treatment for type 1 diabetes with critically labile metabolic control. However, during islet isolation, blood supply is disrupted, and the transport of nutrients/metabolites to and from the islet cells occurs entirely by diffusion. Adequate oxygen supply is essential for function/survival of islet cells and is the limiting factor for graft integrity. Recently, we developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, we incorporated a novel approach based on photosynthetically- generated oxygen. The chamber system was packed sandwich-like with a slab of immobilized photosynthetically active microorganisms (Synechococcus lividus) on top of a flat light source (LEDs, red light at 660 nm, intensity of 8 μE/m2/s). Islet cells immobilized in an alginate slab (500–1 000 islet equivalents/cm2) were mounted on the photosynthetic slab separated by a gas permeable silicone rubber-Teflon membrane, and the complete module was sealed with a microporous polytetrafluorethylene (Teflon) membrane (pore size: 0.4 μm) to protect the contents from the host immune cells. Upon illumination, oxygen produced by photosynthesis diffused via the silicone Teflon membrane into the islet compartment. Oxygen production from implanted encapsulated microorganisms was stable for 1 month. After implantation of the device into diabetic rats, normoglycemia was achieved for 1 week. Upon retrieval of the device, blood glucose levels returned to the diabetic state. Our results demonstrate that an implanted photosynthetic bioreactor can supply oxygen to transplanted islets and thus maintain islet viability/ functionality. Supporting Information for this article is available online at http://www.thieme-connect.de/products [ABSTRACT FROM AUTHOR]

This study examined a possible association of the insulin ( INS) gene with type 1 diabetes (T1D) in patients and controls from four ethnic groups in Israel. We analyzed the distribution of −23 HphI single nucleotide polymorphism (SNP) T/A alleles that correspond to INS variable number of tandem repeat short class I alleles (26–63 repeats) and class III alleles (141–209 repeats), respectively. The −23 HphI T/T genotype was found to be positively associated with T1D in three Jewish groups (Yemenites: 93.9% patients vs 68.8% controls, P = 0.0002; Ashkenazi: 80.6% vs 50.8%, P < 10−4; Ethiopians: 75% vs 40.5%, P = 0.002). The Yemenite healthy controls have the highest frequency of T allele from all Jewish groups studied (83.5% vs 68.8% in Ashkenazi and 64.3% in Ethiopians). The high frequency of a susceptibility allele in the Yemenites is in line with the high incidence of T1D in this population. No association was observed between T1D and the INS gene in Israeli Arabs studied (70.6% vs 66.7%). Variable incidence of T1D among different ethnicities in Israel is largely attributed to heterogeneous genetics. Human leukocyte antigen (HLA) results of our previous studies describing the susceptibility and protective haplotypes were used for combined analysis to determine possible interaction between the HLA and INS loci. Only in the Ashkenazi group such interaction was presented with statistical significance. [ABSTRACT FROM AUTHOR]

Oval cell (OvCs) involvement in regeneration is a well known phenomenon in models of liver injury, however, the activation of these cells following streptozotocin (STZ)-induced diabetes has not been studied yet. Differentiation of liver cells toward insulin-producing cells in diabetes has been reported, but the cell phenotype is still unclear. The aim of the present study was to confirm by immunohistochemical analysis, the activation of OvCs and their ability to express pancreatic beta-cell phenotype in STZ-induced diabetic mice. Using specific anti-A6 antibodies for mouse OvCs, we found a three-fold increase in periportal number and two-fold higher density of OvCs in diabetic livers, when compared to controls. Unlike non-diabetic controls, double staining technique showed co-localization of A6 and proinsulin in the cytoplasm of OvCs of diabetic animals, but no insulin staining was detected, probably reflecting the premature character of OvCs differentiation toward beta-cell-like phenotype. These data add valuable information concerning the nature and the stage of functional maturity of liver cells undergoing differentiation toward beta-cell phenotype in STZ-induced diabetic animals. [ABSTRACT FROM AUTHOR]

Autoimmune diabetes shows extreme variation in age of onset and clinical presentation, although most studies have been done in children with the most severe subtype. Disease risk is strongly associated with HLA-DRB1*0301-DQA1*0501-DQB1*0201 (DR3-DQ2), but it has not been possible to separate the effects of the DR and DQ alleles. We have identified a large Bedouin kindred in which a high prevalence of islet autoimmunity is associated with two different DR3 haplotypes, one carrying the usual DQ2 and the other carrying DQA1*0102-DQB1*0502 (DQ5). Results of prospective follow-up studies indicate that DR3 is associated with the initial activation of islet autoimmunity whereas DQ2 is associated with early-onset and severe clinical disease. The association signals map to a 350-kb interval, thus implicating primary effects for DR3 and DQ2. Overall, our results emphasize the importance of prospective genetic studies that examine the full range of variation in the initiation, progression and expression of autoimmune disease.Genes and Immunity (2007) 8, 628–633; doi:10.1038/sj.gene.6364425; published online 30 August 2007 [ABSTRACT FROM AUTHOR]

Abstract: We have recently shown that repeated streptozotocin (STZ) treatment induces the selection of insulinoma cells (RINmS) with both improved resistance to diabetogenic toxins and functional activity, compared to parental RINm cells. The aim of the present study was to estimate the potential of RINmS cells to maintain their engineered characteristics during in vivo hyperglycemic conditions. It was found that microencapsulation and transplantation into diabetic mice preserved a three-fold higher level of insulin content in selected RINmS cells when compared to the parental ones. Retrieval of transplanted encapsulated cells from the peritoneal cavity of diabetic mice had a significantly higher insulin content and a more intense insulin response to secretogogues in selected RINmS cells when compared to retrieved RINm cells. In conclusion, our results show that RINmS cells do not lose their improved functional characteristics after encapsulation and transplantation into diabetic mice. [Copyright &y& Elsevier]

We have followed-up 35 islet cell antibody-positive first degree relatives of patients with Type 1 (insulin-dependent) diabetes mellitus for an average of 1,300 days with sequential intravenous glucose tolerance tests. At the time of analysis and manuscript submission approximately half (18 of 35) had developed diabetes during follow-up. At initial intravenous glucose tolerance test, 11 had a 1+3 min insulin secretion below the first percentile of insulin secretion compared to 225 similarly studied normal control subjects. Six islet cell antibody positive relatives on follow-up developed an intravenous glucose tolerance test less than the first percentile. Fifteen out of 17 (88%) of these islet cell antibody positive relatives with secretion ever found to be below the first percentile are now overtly diabetic (positive predictive value=88%) and insulin-treated, while only 3 of 18 (17%) without an intravenous glucose tolerance test demonstrating loss of first phase insulin secretion have progressed to diabetes (with approximately 1,300 days of follow-up for both groups relative risk or odds ratio with intravenous glucose p<0.001). tolerance test ever below vs never below the first percentile=38, Intravenous glucose tolerance test response below the first percentile preceded diabetes by an average of 656 days. Even when first phase insulin secretion is below the first percentile, the absolute value of 1+3 min insulin above basal insulin correlates with the time to development of diabetes ( r=0.586, p<0.001). With our current duration of follow-up, the negative predictive value (intravenous glucose tolerance test never below the first percentile) is 83%, and overall accuracy 86%. Incidence rates of diabetes development amongst our islet cell antibody positive relatives with follow-up while intravenous glucose tolerance test is below the first percentile is 0.48 per year (15 conversions to diabetes amongst 17 relatives in 30.8 patient years of follow-up) vs 0.05 per year (three diabetic patients in 55.5 patient years) with intravenous glucose tolerance test greater than the first percentile. [ABSTRACT FROM AUTHOR]

A case of a five-year-old patient with severe rheumatic mitral regurgitation is reported. Intensive anticongestive and corticosteroid therapy were ineffective. Despite the diagnosis of chronic carditis she underwent successful mitral valve replacement with significant improvement of her cardiac status. Valve replacement is indicated in a certain group of patients with rheumatic heart disease which have a poor prognosis on medical therapy alone. [ABSTRACT FROM AUTHOR]

Glucocorticoids tend to lower the intestinal absorption of calcium, leading to a negative calcium balance. A 7-year-old girl with hypoparathyroidism was maintained as normocalcaemic on 1-alpha-hydroxyvitamin D3 (1 alpha D3) and calcium gluconate lactate. During an episode of aplastic anaemia she was treated with prednisolone, with a subsequent dramatic fall of serum calcium despite 1 alpha D3 treatment and serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the high-normal range. Glucocorticoids seem to have interfered directly with cellular events responsible for intestinal absorption of calcium. [ABSTRACT FROM AUTHOR]