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Biomedical subjects

R G Bretzel

Publications and source records attributed to R G Bretzel.

At least 19 recordsLinked to original sources
PubMed1995

Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model.

Primary prevention with aminoguanidine-an inhibitor of advanced glycation end product (AGE) formation--has been successfully employed to prevent diabetic retinopathy in the rat. However, it is unknown whether inhibition of AGE formation is still effective in a secondary intervention strategy. The present study addresses this question by comparing secondary intervention with aminoguanidine with syngeneic islet transplantation in the rat model. After 6 months of diabetes, one group was treated with aminoguanidine (50 mg/100 ml drinking water; D-AG) while another group received syngeneic transplantation of collagenase-ficoll isolated islets by intraportal injection (Tx). After an additional 4 months, both groups were compared to a normal (NC 10) and diabetic (DC 10) control group. Retinal autofluorescence was increased 2.5-fold after 6 months and increased 3.7-fold after 10 months of diabetes (p < 0.001). Aminoguanidine and islet Tx retarded the further accumulation of autofluorescence equally (p < 0.001 vs DC 10), although the values were higher than those observed in DC at 6 months (p < 0.001). Diabetes was associated with a 2.7-fold increase in acellular capillaries after 6 months and a 4.1-fold increase after 10 months. Treatment with aminoguanidine or islet Tx reduced but did not completely attenuate the progression of vascular occlusion (p < 0.001 vs DC 10; D-AG vs DC 6, p < 0.05; Tx vs DC 6, p < 0.01). Both treatments reduced endothelial proliferation (22.4% after 10 months; p < 0.001) and completely arrested pericyte dropout (40% after 10 months; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

The influence of thioctic acid on metabolism and function of the diabetic heart.

Streptozotocin-diabetes as a model for insulin-deficient Type 1 diabetes leads to cardiomyopathy, characterized by a 50% reduced glucose uptake (P < 0.001) and increased lactate and pyruvate levels (P < 0.001), i.e. a reduced glucose utilization by the heart. As thioctic acid (TA) has favourable effects on glucose metabolism, the influence of this drug at two different doses (0.1 mg/ml and 0.5 mg/ml, added to the perfusion medium) was investigated in the heart after 2 weeks of diabetes, using the working rat heart model at physiological workload about 45 min. TA at high doses led to a normalization of glucose uptake (P < 0.001) and glucose utilization, and consequently to a normalization of oxygen uptake (P < 0.001), myocardial ATP levels (P < 0.001) as well as cardiac output (P < 0.05). Whereas a low dose of TA resulted in a normalization of lactate and pyruvate production (P < 0.001), neither a normalization of glucose utilization nor of cardiac output was achieved by this low dosage. Additionally, TA improved at both doses utilization of endogenous glycogen in the diabetic heart (P < 0.001), the latter here already delivering 45% of the utilized glucose. TA acts especially by increasing glucose uptake, glycogen breakdown and glucose oxidation. Thus, metabolic and hemodynamic sequelae of insulin-deficiency in the heart can be corrected by TA. Due to its anti-diabetic effects on cardiac metabolism, TA could be considered an adjuvant therapy in diabetic cardiomyopathy.

Adenosine Triphosphate↗
PubMed1995

The effects of glucagon-like peptide-I (GLP-I) on hormone secretion from isolated human pancreatic islets.

Glucagon-like peptide-I (GLP-I) is a potent incretin hormone that is now considered as a new therapeutic tool in the treatment of diabetes mellitus. In this study we characterized the effects of GLP-I on peptide hormone release from isolated human pancreatic islets. GLP-I stimulated insulin release in the presence of 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 166%; 10 mM glucose + 10 nM GLP-I, 222%) but had only a weak insulinotropic effect (128%) at 2.8 mM glucose. Glucagon release was inhibited by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 72%) and by 10 nM GLP-I at 2.8 mM glucose (67%). Somatostatin secretion was increased by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 166%). GLP-I stimulated somatostatin release in the presence of 2.8 mM glucose (172%). Pancreatic polypeptide (PP) secretion was enhanced by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 236%). GLP-I induced PP release only in the presence of 2.8 mM glucose (184%).

Culture Techniques↗
PubMed1995

Lymphocytic Na(+)-H+ exchange increases after an oral glucose challenge.

The effects of oral glucose challenge on plasma glucose concentration, plasma insulin concentration, arterial blood pressure, cytosolic pH (pHi), cytosolic free Na+ concentration ([Na+]i), and cellular Na(+)-H+ exchange activity were investigated in 16 healthy subjects. The pHi, [Na+]i, and Na(+)-H+ exchange activity were measured in intact lymphocytes by using the fluorescent dye technique. The oral glucose challenge significantly increased plasma glucose, plasma insulin, and the lymphocytic Na(+)-H+ exchange activity, measured as change of pHi per second (control [0 hours], 5.20 +/- 0.53 x 10(-3) dpHi/s; 1 hour after glucose administration, 8.28 +/- 1.07 x 10(-3) dpHi/s; 2 hours after glucose administration, 8.15 +/- 1.18 x 10(-3) dpHi/s; P = .002). The lymphocytic Na(+)-H+ exchange was significantly correlated with plasma glucose concentration (r = .357, P = .041). During steady state euglycemic hyperinsulinemic clamp, the Na(+)-H+ exchange activity was not significantly changed compared with baseline values. The study shows that changes of blood glucose levels can induce an acute increase in Na(+)-H+ exchange activity. Systolic blood pressure and Na(+)-H+ exchange activity were significantly (P < .001) but weakly correlated during an oral glucose challenge.

Adult↗
PubMed1995

[Combined liver-islet transplantation after epigastric exenteration in carcinoma of Vater's ampulla].

A 44 year old female underwent an upper abdominal exenteration because of an adenocarcinoma of the pancreas with liver metastases (T1 N1 M1). Reconstruction was performed by orthotopic liver transplantation and intraportal islet transplantation. Due to initial non function of the first liver graft, a second liver transplantation was performed. Thereafter, the patient received 375,000 islet equivalents of the primary liver donor in addition to 295,400 islet equivalents of another donor. Six months postoperatively, the patient is off insulin except irregular injections of 4-6 units of insulin to protect her from hyperglycemia after lunch. CT scans of the liver do not show any signs of tumor recurrence. Upper abdominal exenteration with consecutive islet transplantation offers a good method of reconstruction after radical surgery in the upper abdomen. The oncological aspects of the procedure have to be further investigated.

Adenocarcinoma↗
PubMed1994

Enterostatin inhibits insulin secretion from isolated perifused rat islets.

The effect of enterostatin on glucose-induced insulin secretion was examined in isolated, perifused rat islets. In the presence of 16.67 mM glucose, there was significant inhibition of insulin secretion at concentrations of 200 nM, 2, 20 and 40 microM enterostatin. In particular, the second phase of insulin secretion was inhibited. With a low concentration of glucose (2.78 mM), there was no significant effect on insulin secretion by enterostatin. The inhibition of insulin secretion exerted by enterostatin may be an important effect in the prevention of insulin resistance.

Animals↗
PubMed1994

Effect of transplantation site and culture pretreatment on islet xenograft survival (rat to mouse) in experimental diabetes without immunosuppression of the host.

Recently, we reported on indefinite islet graft survival in allotransplantation (rat to rat). This was achievable without the use of any immunosuppression by performing transplantation of culture-pretreated (22 degrees C) islets of Langerhans under the renal capsule (r.c.) of chemically induced diabetic recipients. The aim of this study was to test this successful islet modulation technique in a xenogeneic animal model. Six groups of chemically induced diabetic, inbred, C57BL/6J mice received by transplantation either into the liver via the portal vein (i.po.) or under the renal capsule (r.c.) 300-350 either freshly or culture-pretreated (37 degrees C and 22 degrees C) Lewis rat islets without any immunosuppressive therapy. Histology was performed after rejection or post-transplant normoglycaemia (> 120 days) for evaluation of the graft. Transplantation of freshly isolated islets resulted in 75% graft rejection 17 days after transplantation. Using culture pretreatment at 37 degrees C, we noted 75% graft rejection 31 days after transplantation. In contrast, culture pretreatment at 22 degrees C resulted in a marked prolongation of xenograft survival, 75% graft rejection occurring 58 days after transplantation, and in two cases there was indefinite graft survival (> 120 days). Statistical analysis showed a significant prolongation of xenograft survival after culture pretreatment, with the most beneficial effect appearing after low-temperature culture at 22 degrees C (P < 0.05). Interestingly, xenograft survival was markedly prolonged only using the r.c. approach. Statistical comparison revealed a highly significant prolongation using the r.c. as transplantation site compared with i.po. (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group.

PURPOSE: Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated. PATIENTS AND METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks. RESULTS: Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection). CONCLUSION: This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.

Adult↗
PubMed1994

The effect of streptozotocin on the function of fetal porcine and rat pancreatic (pro-)islets.

Streptozotocin (STZ) is a broad spectrum antibiotic with anti-tumor and diabetogenic properties. Although STZ has been studied for many years, the exact mechanism of its diabetogenic action has not yet been fully elucidated. The present study investigated the effect of STZ on both fetal porcine proislets (FPP) and fetal rat islets (FRI) in an attempt to elucidate the diabetogenic effect of STZ on fetal pancreatic beta cells. This study demonstrates that after in vitro exposure of both FPP and FRI for 30 min to 2.2 mM and 4.4 mM STZ, respectively, FPP showed microscopically an intact structure, a spherical shape and a translucent color, while, in contrast, most FRI were disrupted and showed a slight white color with dark centers. Based on these data, we first transplanted FPP and FRI beneath the renal capsules of nude mice. Three to four weeks later, a single dosage of streptozotocin (180 mg/kg) was intravenously administered. Six of the seven nude mice pretransplanted with FPP became diabetic (blood glucose, BG, 308.08 +/- 33.62 mg/dl) within 2-5 days and then gradually achieved normoglycemia 51.56 +/- 7.71 days after STZ injection. After removal of the grafts, all of the six diabetic mice with normoglycemia returned to hyperglycemia (BG > 300 mg/dl). In contrast, all of the five nude mice pretransplanted with FRI persistently maintained hyperglycemia (BG > 300 mg/dl) and died 5 +/- 0.84 days after STZ injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Large-scale production of Ba(2+)-alginate-coated islets of Langerhans for immunoisolation.

Islet xenografts immunisolated in alginate capsules have been proposed by many groups for clinical islet transplantation. However, diffusion limitations and the total volume of microcapsules required for transplantation are, among other things, factors which have so far prevented successful clinical application. In this study, these problems have been overcome by immobilisation of rat and porcine islets in a Ba(2+)-cross-linked alignate matrix using an air jet droplet generator technique in combination with subsequent density-gradient purification. This procedure leads to high yields of islets coated with a tailored, thin layer of cross-linked alginate which protects the islets against cytotoxic compounds present in human plasma. The recovery of encapsulated rat and porcine islets was about 70%. Empty capsules were nearly completely removed. Using this technique, the total volume of the resulting microcapsules increased only by a factor of about 1.5 compared to the volume of free islets. The technique can be used for large-scale production of coated islets.

Alginates↗