Exact parameters for relevant glomerular structures in the course of streptozotocin diabetes in rats with 1 to 18 months' duration were obtained with stereological methods. Renal cortical tissue from diabetic (D) and control animals (C) was processed for light- and electron microscopy and measurements were performed on systematically sampled glomeruli. The thickness of the basement membrane (BM) increased with age in both groups, but the rate of increase was 50% higher in D: 19 +/- 1.2 nm/month (mean +/- SD) vs. 13 +/- 0.9 nm/month, P = 0.0003. The time course of other structural quantities was characterized by the acute changes constituting the glomerular hypertrophy, earlier shown to develop within the first few days of diabetes. All these changes were confirmed in the present study: In the earliest phase the diabetic rats showed an increased total volume of glomeruli, mesangium, and mesangial BM material, as well as an increased surface of the capillary walls. However, none of these differences between the groups showed progression with increasing duration. Mesangial changes corresponding to those of the glomerulopathy in long-term diabetes were not demonstrable within the experimental period. The streptozotocin diabetic rat, therefore, is not useful as a model of advanced diabetic glomerulopathy. But the BM thickness follows the same predictable time course as in human diabetes insofar as moderately advanced cases are concerned. BM thickness is the parameter of choice when a potential effect of different variables on the development of diabetic glomerulopathy is under study.

Islet isolation involves enzymatic digestion of the interstitial matrix and mechanical disruption of the tissue. It is possible that a fundamental change of islet biology resulting from the loss of critical factors required for islet function or survival will occur. Extracellular matrix (ECM) is one of the most important components of the islet microenvironment. Reconstruction of the cell-matrix relationship seems to be effective for improving the loss of differentiated islet structure and function. The purpose of this study was to characterize and compare the effects of collagen gel mixture or Matrigel on β-cell function and islet cell survival. After isolation by the collagenase digestion technique, rat islets were divided and cultured with various types of collagen gel mixture. They were assessed for their glucose-stimulated insulin secretion and cell viability. Glucose-induced insulin secretion of islets cultured with collagen type I gel or a mixture of collagen type I and IV was improved after 11 days in culture. In conclusion, a type of gel composed of collagen type I and/ or type IV as an islet microenvironment is sufficient to maintain glucose responsiveness and may be useful for islet transplantation.

A successfully prevascularized subcutaneous site could be constructed by a tissue bioengineering approach. Xenotransplantation of the agarose/poly (styrene sulfonic acid) mixed gel-based bioartificial pancreas in the prevascularized subcutaneous site could reverse diabetes in mice.

In our study, posttransplantation HLA antibodies were associated with the future absence of OT. A prospective study with more patients is necessary to confirm the predictive value of HLA antibodies for OT.

In order to investigate the pathophysiology of anticonvulsant-induced osteopenia, circulating levels of bone gamma-carboxyglutamic acid-containing protein (Bone Gla Protein: BGP) and urinary excretion of BGP were measured in 16 children on chronic anticonvulsant therapy and in 12 control children. Using microdensitometry analysis, osteopenia was found in 25% of the anticonvulsant therapy group, but it was not observed in the control group. Serum BGP and A1-P levels were significantly increased in the anticonvulsant group compared with the control group (P less than 0.05 and P less than 0.01, respectively), and a positive correlation was found between serum BGP and A1-P levels (P less than 0.05). Urinary excretion of BGP and hydroxyproline showed an increase in the anticonvulsant group, but it was not statistically significant. On the other hand, there was no significant difference between the two groups in serum levels of vitamin D metabolites, PTH, calcitonin, Ca, or P or in urinary excretion of Ca or P. It is suggested, therefore, that the increased BGP level in children receiving anticonvulsant therapy is a reflection of high bone turnover due to anticonvulsant drug complications.

Our results indicate that the potential use of the SDT rat for diabetes study and the positive effect of PTx performed before the "point of no return" could prevent and cure diabetic ocular complications.

The subcutaneous space is a potential site for clinical islet transplantation. Even though there are several advantages, poor blood supply at this site mainly causes failure of islet survival. In this study, angiogenesis was induced in advance at the diabetic rats subcutis for islet transplantation by implanting a polyethylene terephthalate (PET) mesh bag containing gelatin microspheres incorporating basic fibroblast growth factor (bFGF) (MS/bFGF) and a collagen sponge. The bFGF was incorporated into gelatin microspheres for controlled release of bFGF. As controls, a PET mesh bag with or without either collagen sponges or MS/bFGF was implanted at the subcutaneous site of diabetic rats. Macroscopic and microscopic examinations revealed the formation of capillary network in and around the PET mesh bag containing MS/bFGF and collagen sponges 7 days after implantation when compare with other control groups. When tissue hemoglobin level was also measured, a significantly high level of hemoglobin amount was observed compared with that of control groups. When allogeneic islets mixed with 5% agarose were transplanted into the prevascularized rat subcutis, normoglycemia was maintained for more than 40 days, while other control groups were ineffective. This study demonstrated that combination of gelatin microspheres incorporating bFGF and collagen sponges enabled the mesh to induce neovascularization even at the subcutaneous site of streptozotocininduced diabetic rats, resulting in improved function of islet transplantation.

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