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Biomedical subjects

R Assan

Publications and source records attributed to R Assan.

At least 73 records · Page 4Linked to original sources
PubMed1985

Functional and morphological modifications induced in rat islets by pentamidine and other diamidines in vitro.

The antiprotozoal drug pentamidine can be toxic to islet cells in vivo and in vitro. Rat islets were exposed to pentamidine (mesylate and isethionate salts) and six other structurally related diamidines. The beta-cell response to arginine + theophylline was suppressed by pentamidine (10(-2) mmol/l) while the glucagon and somatostatin secretions persisted. All diamidines tested suppressed the beta-cell function, with a log-dose-response proportionality, the mesylate compound being more potent than pentamidine isethionate, and the lipophilic analogs more than the hydrosoluble diamidines. Electron microscopy revealed distinct morphological alterations in islets exposed to pentamidine, the intensity of these changes being dose-and time-dependent, and the beta cells more severely damaged than the non-beta cells. 51Cr-labelled islet cells and RIN 5 F cells consistently appeared more sensitive to pentamidine cytotoxicity than rat fibroblasts, myeloma cells and hepatocytes. The pentamidine-induced suppression of beta-cell function was not, in conditions tested, affected by the presence of nicotinamide and the hexose concentration in the medium. The kinetics of islet damage were slower than those of streptozotocin and alloxan-induced islet damage. The present study confirms that pentamidine is selectively toxic to islet beta cells, with some features distinct from the alloxan and streptozotocin toxicities to these cells. The mechanism of this process and its precipitating factors in vivo need clarification.

Amidines↗
PubMed1985

Anti-islet cellular and humoral immunity, T-cell subsets, and thymic function in type I diabetes.

UNLABELLED: Peripheral lymphocyte subsets were enumerated, using OKT monoclonal sera, in 56 diabetic (43 adults and 13 children) and 20 control subjects. Concomitantly, anti-islet humoral and cellular immunity was tested in vitro and serum thymulin level was measured. In the newly diagnosed patients (less than 30 days; 18 cases), the percent of OKT4+ and OKT8+ cells was reduced, the OKT8+ depletion being particularly pronounced in children. Tests for cellular immunity were positive in 83% of the newly diagnosed diabetic subjects and anti-islet cytotoxic antibodies were detected in 50%. The serum thymulin level was decreased in 2 children. Later on in the course of the disease, a marked reduction in OKT3+, OKT4+, and OKT8+ cell percentage was observed, the mean OKT4/OKT8 ratio being normal or lower than normal. The percent of antibody-positive sera rose to 64%, while anti-islet cellular immunity was detectable in 54%. When extrapancreatic manifestations of probable autoimmune nature were present, anti-islet cellular immunity was detected in 100% of cases, accompanied by cytotoxic antibodies in 54%. CONCLUSIONS: (1) the magnitude of T-cell depletion and/or imbalance in diabetic subjects depended mainly on the duration of the disease, (2) anti-islet cellular immunity was the anomaly most frequently detectable, and (3) a decrease in serum thymulin level was infrequently detected.

Adolescent↗
PubMed1985

Time course of islet cell antibodies in diabetic and nondiabetic BB rats.

The BB rat develops a spontaneous type I diabetic syndrome with anti-islet autoimmunity. Sera from diabetic and nondiabetic BB rats (from diabetes-prone litters), nondiabetic BB rats (from low-risk lines), and nondiabetes-prone Sprague-Dawley rats were collected twice a week from age 40 days to 160 days. Sera were tested for: (1) complement-dependent toxicity to 51Cr-labeled islet cells in vitro; (2) immunoglobulin binding to RIN-5 F insulinoma cells; and (3) ability to selectively suppress insulin secretion from normal islets in vitro. All sera from rats that subsequently became diabetic or glucose-intolerant were toxic to islet cells from various rat strains in the presence of complement. They were toxic neither to hepatocytes nor to fibroblasts. The toxic potency was associated with the globulin fraction. It was, in most cases, maximal either before or immediately after the onset of the disease. Sera from the nondiabetes-susceptible BB rats and the rats which, in diabetes-prone litters, died too early to be classified tended toward greater toxicity to islets. Immunoglobulins from diabetic sera bound to RIN-5 F cells more than did the serum globulins from other groups, their maximal binding capacity occurring after the onset of diabetes. Furthermore, BB diabetic sera were capable of selectively inhibiting the insulin secretion from normal rat islets in vitro either in the presence or, in some cases, in the absence of complement. The A- and D-cell functions were not suppressed. The combination of such results suggests the presence of one or more antibodies capable of binding to beta cells, inhibiting their function, and inducing their lysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Survival and rehabilitation after total pancreatectomy. A follow-up of 36 patients.

Thirty-six totally depancreatectomized patients were followed up for 4-124 months. Pancreatectomy had been performed because of fulminant pancreatitis (in 10), chronic hyperalgic otherwise untractable pancreatitis (in 7), exocrine carcinoma of the pancreas (in 16), cystadenocarcinoma of the pancreas (in 2) and insulinoma (in 1). The longest survival duration was in chronic pancreatitis patients: 57 +/- 17 months. A normal socio-professional reinsertion was obtained in 16 patients, mainly those with non-malignant pancreotopathies. At the end of the survey, ten of the carcinoma patients had died, versus none in the other groups. Diabetes mellitus was characterized by the absence of ketonuria, and the frequent occurrence of hypoglycemia (in 15 patients) and infection (in 6). Malabsorption caused osteomalacia in one patient.

Acute Disease↗
PubMed1985

[A broad educational approach to insulin-dependent diabetics].

Self monitoring of diabetes requires technical knowledge and suitable diabetes oriented behaviour; the latter arises from the patient's psycho-affective functioning, maturity and self sufficiency. A group of 9 insulin dependent ambulatory, adult, diabetics met 15 times over 5 months. The somatic and psycho-affective aspects of the disease were approached by an original methodology. Group animation was focussed on the participants themselves. Dynamic mobilisation of the persons was sought by listening to their explicit and implicit requests, by acting out (case studies and role-playing), by restatement and questioning. Diabetes oriented and psycho-affective behaviours were assessed on the basis of questionnaires and statements. At the end of the study, the psycho-affective attitude of the participants towards their illness was modified. The aggressiveness, mockery and rejection of diabetes and diabetics, initially noted, were progressively replaced by self-awareness and acceptance. As a result, better adjustment of technical behaviour responses was noted. Without precluding any psychodynamic explanation (reunification of the person), this study suggests that the participant's reactions towards their own image can be improved with consequential educational benefit.

Adult↗
PubMed1984

Haemoglobinopathies: a pitfall in the assessment of glycosylated haemoglobin by ion-exchange chromatography.

Total glycosylated haemoglobin was determined by a minicolumn ion-exchange chromatography technique (Bio-Rad) and correlated with the mean of fasting and post-prandial blood glucose values for the preceding 6 weeks. In 360 diabetic subjects, free of congenital haemoglobinopathies and other detected causes of haemoglobin A1 misinterpretation (reference diabetic group), a highly significant correlation was established between haemoglobin A1 and glucose (y = 0.54 X +4.91; r = 0.791; p less than 0.01). In 28 of the 29 patients with heterozygous haemoglobinopathies (HbS, C, D, E), the apparent haemoglobin A1 values were lower than expected according to the 95% confidence limits of the diabetic reference group. The apparent haemoglobin A1 value was above these limits in patient 29, with beta thalassaemia. Patients with inappropriate glycosylated haemoglobin values should be investigated for causes of haemoglobin A1 misinterpretation, in particular, haemoglobinopathies.

Blood Glucose↗
PubMed1984

Endocrine cells in the anal canal.

Endocrine cells are normal inhabitants of the anal canal. While numerous endocrine cells are distributed throughout anal ducts and crypts, few are dispersed in the anal transitional zone. All these cells were characterized as serotonin-storing cells, and this endocrine profile is quite distinctive from that of adjacent mucosae. Rectal epithelium contains serotonin, somatostatin, enteroglucagon, BPP and HPP immunoreactive cells; endocrine cells are lacking in the pectinal folds and perianal skin. It is suggested that this distinctive hormonal profile may be regarded as a specific marker of this anal territory. The same pattern is found in the fetal transitional lining of anal canal. Evidence of serotonin-storing cells in the transitional epithelium of anal glands and crypts and in the ATZ epithelium, reinforces the homology between these linings and urothelium. The presence of a similar fetal epithelium implies that ATZ epithelium in adults is not necessarily metaplastic. All derivatives of the cloaca may therefore share the same endocrine profile.

Anal Canal↗
PubMed1984

A new technique for hepatic portal vein catheterization in freely moving rats.

To perform kinetic studies of pancreatic hormones in freely moving rats, we have designed a new technique for hepatic portal vein catheterization through the left branch of the portal vein. Rats were followed up for 14-38 days. Catheter patency allowed blood sampling in 86% of rats on postoperative day 8 and in 55% on day 12. Rat growth, liver functions, and regional blood flows (measured with radiolabeled microspheres) were normal. In freely moving rats fasted for 16 h, portal venous concentrations in the basal state were: glucose, 112 +/- 4 mg/dl; insulin, 67 +/- 10 microU/ml; and glucagon, 480 +/- 74 pg/ml. These values remained stable for a 1-h period. Intravenous glucose infusion induced a biphasic insulin release, significant from the 1st min of infusion on, and a significant decline in glucagon level. Intravenous arginine stimulated both A and B cells. The portoperipheral hormone concentration gradient, which was detected in the basal state, increased during arginine infusion, particularly in regard to insulin. Ingestion of a mixed meal induced an early glucagon release and a sustained rise in insulin and glucose concentrations.

Animals↗
PubMed1984

Glucagon and insulin secretion and their biological activities in hypothermic rats.

To clarify the impact of hypothermia on the hormonal control of glucose metabolism, rats were rendered hypothermic (25 C) after catheterization of the portal vein. Glucose, insulin, glucagon, and catecholamine concentrations were serially monitored, and the regional blood flows were measured, allowing the estimation of hormone outputs. Hypothermia reduced the portal blood flow by 50% without changing arterial blood pressure, blood gases, or pH. Portal plasma insulin secretion dropped (0.05 +/- 0.01 vs. 0.23 +/- 0.04 mU/min), and glucagon secretion increased (0.81 +/- 0.18 vs. 0.38 +/- 0.10 ng/min). The B cell responses to glucose, arginine, and glucagon were abolished, while the A cell response to arginine was not significantly affected. Glucose intolerance was apparent after iv glucose or arginine loads. Haloperidol and to a lesser extent phentolamine suppressed the cold-induced glucagon rise. Phentolamine and to a lesser extent haloperidol alleviated the cold-induced suppression of insulin release. Propranolol, naloxone, and atropine were relatively inactive. The cold-induced glucose intolerance was not corrected by phentolamine treatment. A marked resistance to iv insulin was apparent in these rats, which is in contrast to a normal sensitivity to iv glucagon.

Animals↗
PubMed1984

Anti-beta-cell immunity in insulinopenic diabetic dogs.

Anti-islet immunity was studied in six spontaneously insulin-dependent diabetic (IDD) dogs, using mouse islets of Langerhans cells as targets, in vitro. Insulinopenia was demonstrated in all dogs by an i.v. glucose tolerance test. A significant lymphocytopenia was detected in the peripheral blood of this diabetic group. Pancreatic tissue from one of these animals was obtained shortly after death and the islets displayed a marked loss in beta cells without significant changes in the other types of islet cells. No insulitis was observed. Circulating mononuclear cells from the diabetic dogs induced an increased basal insulin (IRI) release from islet cells and a suppressed stimulated IRI release. Damage to or depth of beta cells may account for these findings. The stimulated IRI release was also suppressed when islets were incubated with the diabetic sera + complement, while the D-cell response to arginine was not altered, and the A-cell response was reduced but not abolished. A lysis of islet cells in the presence of IDD sera + complement was demonstrated by an increased release of 51Cr from labeled cells. These anomalies were observed neither when complement was heat-inactivated nor in the presence of control sera + complement. Canine IDD may be a new animal model for the study of anti-islet cellular and humoral immunities.

Animals↗
PubMed1984

Anti-pancreatic immunity. In vitro studies of cellular and humoral immune reactions directed toward pancreatic islets.

It has been suggested that the immune system may be responsible for the destruction of insulin secreting cells in some types of diabetes. In order to test this hypothesis, we studied the consequences of immune-mediated reactions on the function of pancreatic islet cells in vitro. A model was set up in vitro where mouse pancreatic islet cells are exposed to human lymphocytes or sera + complement then stimulated for the release of insulin or glucagon. A selective inhibition of insulin secretion, but not of glucagon secretion, was observed in the presence of lymphocytes from 37 out of 40 insulin-dependent diabetic (IDD) patients and in the presence of sera (+ complement) from 22 out of 40. Lymphocytes were found inhibitory in almost all patients in both groups, with and without associated autoimmune diseases. In contrast, inhibitory sera were observed almost only in patients with associated autoimmune diseases or recent onset diabetes. The selective inhibition of insulin secretion, but not of glucagon secretion, suggests that lymphocytes or sera may be involved in a destructive process of insulin secreting cells in vivo. This cell-mediated effect depends on direct T lymphocyte cytotoxicity, rather than antibody-dependent cell cytotoxicity, as suggested by the lack of any effect of aggregated immunoglobulins on the reaction. In contrast, when C57BL/6 mice were immunized by mastocytoma cells from a DBA2 strain, their lymphocytes and sera blocked both secretions of insulin and glucagon when incubated in vitro with DBA2 islet cells. This non-selective inhibition may be due to anti-H2 immunity, rather than immunity directed against insulin secreting cells.

Adolescent↗
PubMed1984

Haemoglobinopathies, malaria, and other interferences with HBA1 assessment.

Total glycosylated haemoglobin (HbA1) was determined by a rapid minicolumn chromatography technique in 438 diabetic patients and correlated with the mean of fasting and post-prandial blood glucose values for the preceding six weeks. In 360 of them, free of congenital haemoglobinopathies and other detected causes of HbA1 mis-interpretation (reference group), a significant correlation was established between the HbA1 and glucose values: y = 0.54 X + 4.91; r = 791; (p less than 0.01). In 28 of the 29 patients with heterozygous haemoglobinopathies (Hb S = 17; Hb C = 8; Hb D Pundjab = 1; Hb E = 2) the apparent HbA1 values were inappropriately low. The apparent HbA1 value was above the 95% confidence limits in the 29th patient, with beta thalassaemia. In 10 out of 14 diabetics with recurrent hypoglycemic attacks, the HbA1 value was lower than the 95% confidence limits of expected values. Out of 21 diabetics with a shortened red cell lifespan (occult blood losses: 10; haemolysis: 11) 15 displayed a lower than expected HbA1 value. Among these was a diabetic patient with malaria and severe anaemia. Out of 14 diabetics with severe chronic renal failure only 3 presented with apparent HbA1 values above the 95% confidence limits.

Adult↗
PubMed1983

Effect of insulin replacement on intermediary metabolism in diabetes secondary to pancreatectomy.

Patients with diabetes due to pancreatectomy have metabolic features different from Type 1 (insulin-dependent) diabetes after insulin withdrawal. Whether or not glucagon by itself or combined glucagon-insulin absence are responsible for this metabolic behaviour is unknown. This study was carried out to evaluate the ability of insulin replacement to abolish differences between patients with Type 1 diabetes and patients with diabetes due to pancreatectomy. We studied the diurnal patterns of intermediary metabolites, free insulin, and glucagon using the Biostator (glucose-controlled insulin infusion system) and intensive subcutaneous insulin therapy in five patients after total pancreatectomy, five after partial pancreatectomy and seven patients with Type 1 diabetes. All were studied for 24 h after an overnight period of normoglycaemia. Insulin requirement was lower in the patients with total pancreatectomy than in patients with partial pancreatectomy or Type 1 diabetes during both types of insulin treatment (p less than 0.05). Blood glucose and free insulin were similar in all the groups in both conditions. Immunoreactive glucagon was higher in the patients with diabetes secondary to pancreatectomy than in Type 1 diabetic patients. However, glucagon levels did not increase after arginine infusion in the patients with total pancreatectomy, and column chromatography of blood samples from two totally pancreatectomized patients showed no significant levels of immunoreactive pancreatic glucagon. Non-esterified fatty acids and ketone bodies were similar during Biostator and intensive subcutaneous insulin therapy. By contrast, gluconeogenic precursors (lactate, pyruvate, alanine and glycerol) were higher in patients with total pancreatectomy than in patients with partial pancreatectomy and Type 1 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Pentamidine, a new diabetogenic drug in laboratory rodents.

The antiprotozoal drug, pentamidine, has been reported to induce hypoglycaemia associated with inappropriately high plasma insulin concentrations, followed by insulin-dependent diabetes mellitus. It has been suggested that this drug can be toxic to the islet B cell, inducing early cytolytic release of insulin leading to B cell destruction. In order to test this hypothesis, mouse and rat islets were incubated with pentamidine at concentration range of 5 x 10(-11) to 5 x 10(-3) mol/l and exposure times of 3-48 h. The B cell responses to glucose + theophylline and to arginine were suppressed by pentamidine, while insulin release in non-stimulatory conditions was increased. These effects were dose-dependent, time-dependent and irreversible. They were significant for 5 x 10(-7) mol/l pentamidine, which is a concentration relevant to therapeutic uses. These effects developed more slowly than the toxic effects of streptozotocin and alloxan at the same molar concentration in vitro. 51Chromium release and Trypan blue exclusion tests support the hypothesis that pentamidine produces islet cell necrosis.

Amidines↗
PubMed1983

Ovarian-adrenal interactions in regulation of endocrine pancreatic function in the rat.

The interference of adrenal hormones with the oestradiol-induced modifications of endocrine pancreatic function remains controversial. For this reason, we compared sham-operated, ovariectomized and adrenalectomized-ovariectomized female rats. In each group, control and 17-beta-oestradiol-treated rats (0.1 mg/day for 14 days) were studied, the latter group being compared with similar rats treated with corticosterone (0.4 mg/day). Oestradiol treatment induced hypoglycaemia and hyperinsulinism in basal and glucose-stimulated states, and hypoglucagonaemia. The presence of adrenal glands was necessary for the full expression of oestradiol effects on pancreatic islet B cells: in adrenalectomized-ovariectomized rats, oestradiol treatment induced an unexpected decrease in insulin response to intravenous glucose, and in pancreatic insulin content. Corticosterone treatment partly restored the oestradiol-induced rise of plasma insulin, and restored the B cell response to intravenous glucose. A permissive action of glucocorticoids may be a prerequisite for the effect of oestrogens on B cells. Since oestrogens by themselves augment the plasma corticosterone level, the insulinotropic effect of oestrogens may be partly mediated by the increase in endogenous corticosteroids. In contrast, oestradiol seems to suppress islet A cell function.

Adrenal Glands↗