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Biomedical subjects

R G Bretzel

Publications and source records attributed to R G Bretzel.

At least 235 records · Page 13Linked to original sources

Fish oil-enriched diet and reduction of low-dose streptozocin-induced hyperglycemia. Inhibition of macrophage activation.

Repeated low doses of streptozocin (STZ; 40 mg/kg, 5 injections/day) induce hyperglycemia in certain strains of mice after a latency of 1 wk. Omega-3 polyunsaturated fatty acids (omega 3FA) have been reported to suppress immune processes by blockade of the cyclooxygenase pathway of arachidonic acid metabolism. We investigated the effects of diets high in omega 3FA on the development of diabetes in the low-dose STZ-induced diabetes (LDSTZ-D) model. Male C57BL/6J mice were on a fish oil diet (FOD) as a source of omega 3FA 8 wk before STZ injection. Controls received laboratory chow only or a coconut oil diet (COD). Blood glucose levels in FOD mice were reduced (12.5 vs. 28 mM for COD mice, P less than .001) 60 days after STZ injection with a diet in which 20% of the calories were from fish oil. In FOD mice, immunohistology showed reduced numbers of class II antigen-expressing cells in pancreatic islets followed by a decreased extent of insulitis. FOD significantly decreased the number of Fc receptor-negative dendritic cells in cytospin preparations of islets isolated from diabetic mice. Interleukin 1-like activity of peritoneal exudate cell supernatants isolated from mice on FOD was reduced. FOD did not improve insulin secretion of isolated islets from LDSTZ-D mice. These data indicate a beneficial effect of FOD on the immune component of the mouse LDSTZ-D model.

Animals↗

[Islands of Langerhans of cattle--potential donor tissue for clinical islet transplantation?].

A standard method for bovine islet isolation has been developed. The mean islet yield per gram pancreas obtained from the last twelve consecutive glands was 2,098 +/- 292 representing an insulin recovery of 36.1 +/- 6.5%. The static incubation of freshly isolated bovine islets in the presence of glucose resulted in a less distinct increase of insulin secretion than in the presence of free fatty acids. Nevertheless, xenotransplantation of bovine islets to immunosuppressed C57BL6J mice did reverse streptozotocin-induced diabetes for 2 to 6 days.

Animals↗

[Islet transplantation in type II diabetes mellitus--model of the spontaneous diabetic Cohen rat].

The spontaneous diabetic Cohen-rat is one of the few animal models of the diabetes mellitus Type II (NIDDM). A spontaneous diabetic animal line and a diabetes-resistant line originated from a parental lineage by genetic selection with regard to the glucose tolerance on condition of feeding of a saccharose-rich and copper-poor diet. In each case 1000 islets of the diabetes-resistant line were transplanted in 28 animals of the diabetic line. Body weight, blood-sugar concentration, glucosuria, glucose tolerance, and the HbA1 were normalized after the transplantation. The serum levels of insulin and glucagon increased. These results emphasize etiopathogenetic importance of the islets of Langerhans in this animal model.

Animals↗

[Principles of immunotherapy in insulin-dependent diabetes mellitus].

There is now convincing evidence that insulin-dependent (Type 1) diabetes mellitus is an immunological disease. This is derived from observations of a genetically determined predisposition, an association of recent-onset diabetes with viral infections, an inflammatory cell infiltrate affecting the islets of Langerhans, autoantibodies against islet cells, insulin, insulin receptors, and other organ-specific or non-organ-specific antigens, as well as abnormalities of cell-mediated immunity and of non-antigen specific mediators. Finally, recurrent diabetes in cases of pancreas transplantation in monozygotic twins discordant for insulin-dependent diabetes underlines the influence of an autoimmune insulitis. The current concept of the aetiopathogenesis of most cases of insulin-dependent diabetes is that in genetically susceptible individuals any form of damage to beta cells by viral, toxic, dietary or other environmental factors may initiate beta cell destruction and/or aberrant antigen expression, followed by a self-perpetuating, mostly cell-mediated autoimmune destruction of the insulin-producing cells. Successful immunoprevention in autoimmune diabetes models, on the basis of these recent concepts, led to the assumption that immunotherapy by means of immunomodulative or immunosuppressive drugs might be a possible tool in the treatment of patients with recent onset insulin-dependent (Type 1) diabetes mellitus.

Animals↗

Different effect of two immunomodulating agents cyclosporin A and ciamexon on the insulin metabolism of cultured mouse islets.

Ciamexon is a new immunomodulating agent with promising effects in treatment of newly-diagnosed insulin dependent diabetic patients. Ciamexon seems to have fewer adverse toxic properties than Cyclosporin A. Therefore, the effects of both substances on islet cell function were studied. Collagenase-isolated mouse islets were cultured free-floating for 3 or 7 days in medium RPMI 1640 plus 10% fetal calf serum in the presence of Cyclosporin A or Ciamexon (0.1 microgram/ml, 1 microgram/ml). Culture of the islets in the presence of 0.1 microgram/ml Ciamexon neither reduced the number of viable islets nor impaired insulin secretion as was found in Cyclosporin A. These results should be taken into account when treating early Type 1 diabetes or when transplanting islet cells.

Adjuvants, Immunologic↗

Ciamexon in the low dose streptozotocin induced diabetes of mice.

This article is concerned with suppression of the development of diabetes experimentally induced by multiple injections of subdiabetogenic doses of streptozotocin (4 x 45 mg/kg/d) in mice (CD 1 and C57B16). Streptozotocin injections were followed by hyperglycemia and mononuclear cell infiltration of islets (insulitis). Ciamexon is a new immuno-modulating agent with promising effects in experimental models of autoimmune diseases and practically no toxic side effects. When Ciamexon was given before streptozotocin treatment blood glucose levels in the parenteral glucose tolerance test were suppressed in a dose dependent way. 60 days after streptozotocin application the percentage of islets showing insulitis or even necrosis was reduced in the Ciamexon treated group compared to the streptozotocin only group. In contrast, Cyclosporin A had a detrimental effect on diabetes in this model although blood levels were proved to be in the therapeutic range. From these results we conclude that Ciamexon should be tested for its effect in human type I diabetes.

Adjuvants, Immunologic↗

Assay for thyroid growth stimulating immunoglobulins: stimulation of [3H]thymidine incorporation into isolated thyroid follicles by TSH, EGF, and immunoglobulins from goitrous patients in an iodine-deficient region.

Estimations were carried out of [3H]thymidine incorporation during culture of isolated porcine thyroid follicles in the presence of standard TSH or epidermal growth factor (EGF) both alone and together with anti-TSH or anti-EGF serum, and of immunoglobulins fractionated from the sera of patients from our endemic goitre area with iodine deficiency. A significant stimulation of thymidine incorporation was exerted by TSH when thyroglobulin was present in the culture medium, and also by EGF. TSH stimulation was abolished by anti-TSH serum, in contrast to the effect of EGF. Anti-EGF serum, on the other hand, blocked the effect of EGF, but not that of TSH. The sera of 20 out of 72 patients (27%) with euthyroid goitre (not operated on) and of ten out of 26 patients (38%) with recurrent euthyroid goitre contained immunoglobulins stimulating thyroid growth (TGI). There was no correlation of TGI with other thyroid antibodies. TGI have to be regarded as a pathogenetic factor of euthyroid goitre also in patients from an endemic region especially in recurrent cases.

Animals↗