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Biomedical subjects

P Petkov

Publications and source records attributed to P Petkov.

At least 19 recordsLinked to original sources

S 15261, a novel agent for the treatment of insulin resistance. Studies on Psammomys obesus. Effect on pancreatic islets of insulin resistant animals.

A histological study has been conducted on pancreata from insulin resistant sand rats treated with S15261. As previously shown, standard laboratory chow induced dietary hyperinsulinaemia, insulin resistance and hyperlipaemia in sand rats (Psammomys obesus). Degranulation, vacuolization and even necrosis of beta-cells were observed in these animals. These changes were often accompanied by fibrosis and lymphocytic infiltration. Insulin and amylin immuno-reactivity of beta-cells was markedly decreased whilst glucagon secreting cells were localized now in the centre of the islets. Chronic treatment with S15261, a compound able to restore insulin sensitivity in insulin resistant animals, promoted the regranulation of the beta-cells and maintained the usual cytoarchitecture and integrity of the islets.

Animals↗

[Immunohistochemical studies of the pancreas in newborns with diabetic fetopathy].

The number and the size of the Langerhans islets in the pancreata of most of investigated cases with diabetic foetopathy is increased (polynesia and macronesia). The B endocrine cells are immunoreactive for both insulin and IAPP, the reaction for IAPP being weaker in comparison with the controls. In one of the cases (the mother with long history of treated type 1 diabetes, who died during delivery) no presence of insulin-immunoreactive of PAF positive B cells is discovered. The reactivity for glucagon and somatostatin in the pancreata with diabetic foetopathy is found to be similar to the controls. In the vicinity of some islets lymphoid cell infiltrations are observed.

Amyloid↗

Latent autoimmune diabetes mellitus in adult humans with non-insulin-dependent diabetes: is Psammomys obesus a suitable animal model?

Recent data suggest that in a proportion of NIDDM patients there is a slowly evolving insulitis which results in a latent autoimmune diabetes leading to full insulin-dependence. Many animal models exist of NIDDM but none have reported the spontaneous existence of a similar phenomenon. We have re-examined the histology of pancreata from a few Psammomys obesus who had become insulin-dependent in the late stages of NIDDM. We report here the unexpected finding of the presence of insulitis in these animals and suggest that they could be a model for the clinical observation of latent IDDM in NIDDM patients.

Adult↗

Islet amyloid polypeptide in Psammomys obesus: lack of correlation between insulin resistance and plasma IAPP levels.

Sand rats (Psammomys obesus) develop insulin resistance and diabetes when given a standard laboratory diet. We have examined the presence of islet amyloid polypeptide (IAPP), or amylin, in these animals. IAPP is present in the beta-cells of pancreatic islets, its localization and intensity of immuno-reactivity are, thus, similar to that of insulin. In insulin resistant Psammomys obesus, insulin and IAPP immuno-reactivity in pancreas are markedly decreased, plasma insulin levels are 20-fold higher than in controls but IAPP levels are not different from those of normal animals. Therefore, insulin resistance in Psammomys obesus does not appear to result from an elevated plasma IAPP level nor from development of amyloid deposits.

Amyloid↗

[Morphological changes in the pancreas after ligation of the excretory duct].

The rabbit pancreatic structure at histological and ultrastructural level, in different intervals after ligature of pancreatic duct, was studied. Changes in the exo- and endocrine parenchyma were observed. Canalicular structures and conjunctive tissue replace the destroyed acinar cells. In some of the islets the B cells are degranulated or necrotic. Some islets contain infiltrations of lymphocytes, macrophages and granulocytes. Cavities formed by necrotic endocrine cells could appear. The A and B cells proliferation is observed in the new-formed clusters of endocrine cells and ductless. The mechanism of this process is similar to that of the islet formation during the embryonic development or in nesidioblastosis, but they are never transformed in the definitive islet of Langerhans.

Animals↗

[Morphological and morphometric studies of the pancreas in type-2 diabetes mellitus].

The authors investigated histologically and immunohistochemically 60 cases with diabetes mellitus type 2. By means of the morphometric method of Weibel et al. (1969) they established diminished volume density of the insular tissue in total pancreas. The morphologic and morphometric data revealed evidence that diabetes mellitus most probably presented a heterogeneous group of pancreatic lesions manifested by disturbances of carbohydrate homeostasis.

Diabetes Mellitus, Type 2↗

Immunohistochemical and electron microscope studies of rat islets of Langerhans one month after adult thymectomy.

Ultrastructural and quantitative immunocytochemical studies of rat pancreata were carried out 1 month after adult thymectomy. The proportions of insulin-, glucagon-, and somatostatin-immunoreactive cells in the pancreas were estimated on paraffin sections using the unlabelled peroxidase-antiperoxidase method. Relative islet volume, islet size and number were determined on hematoxylin and eosin stained sections. A moderate increase of the islet volume on account of size was found in the pancreas of the thymectomized rats. The proportion of insulin-immunoreactive cells was also elevated. Ultrastructural studies showed a rich supply of secretory granules in most beta-cells. Mixed beta-endocrine-acinar cells were often observed. Mitotic figures were found in single beta-cells. The blood glucose level was in the normal range. The findings suggest a moderate stimulation of beta-cell secretory activity after thymectomy which is not associated with elevated blood glucose levels.

Animals↗

A morphological and immunohistochemical investigation of endocrine pancreata from obese ob+/ob+ mice.

There is a marked difference in insulin secretion between the ob+/ob+ obese mouse and its non-obese littermate. Numerous peptides have been implicated in the modification of postprandial insulin secretion. In this study, the morphological and immunohistochemical studies of the genetically obese mouse (ob+/ob+) pancreata were compared with control littermates. Additionally, the distribution of gastric inhibitory polypeptide, somatostatin, glucagon, and insulin immunoreactive cells was also quantitated. Hyperglycemia and hyperinsulinemia were verified in the obese mice. The control animals had some islets and ductules with mononuclear infiltrations of a possible immune character. The obese individuals had a marked increase in both number and size of the islets of Langerhans compared with lean controls. The insulin immunocytochemical reaction in the obese pancreatic beta-cells was weaker than that of controls, as was the aldehyde-fuchsin reaction. The glucagon, gastric inhibitory polypeptide, and somatostatin containing cells were intermingled with the beta-cells. In contrast, the control animals showed a peripheral localization of these cell types. The morphometric analysis of the obese pancreas showed a decreased proportion of non-beta cells within the islets but not in total pancreatic volume in comparison with controls. The obese mouse also had cavities filled with eosin-stained material among numerous beta-cells. No complete epithelial lining distinguished these formations from the surrounding islet cells. The content of the cavities was not stained by any of the immunocytochemical reactions applied. In conclusion, the pancreatic islets of the ob+/ob+ mouse show marked differences in both morphological and immunocytochemical characteristics if compared with control littermates. These differences in architecture may be related to the eventual development of diabetes mellitus in the ob+/ob+ mouse.

Animals↗

Morphological characteristics of the endocrine pancreas in alloxan diabetes after cyclosporin A administration.

Histological, immunocytochemical, morphometric and electron microscope studies were carried out on the pancreas of alloxan diabetic rats pretreated with cyclosporin A. High mortality, severe destruction of pancreatic B-cells and presence of sporadic mononuclear infiltrations in islets and around excretory ducts were observed. The results obtained show that cyclosporin A potentiates the toxic effect of alloxan on the pancreatic B-cells.

Animals↗

Diabetes mellitus in sand rats (Psammomys obesus): microangiopathy during development of the diabetic syndrome.

The purpose of the study was to investigate the development of microangiopathic complications in North African sand rats with diabetes induced by a long-term standard laboratory diet. Hyperinsulinaemic rats, whether non-diabetic obese or diabetic, developed capillary basement membrane (CBM) thickening in the skin; in insulin-dependent animals, this change was diffuse. Many PAS positive areas were demonstrated in skeletal muscle and myocardium, together with evidence of microangiopathy; the primary myocardial lesion in insulin-dependent disease was ischaemic fibrosis. The kidney was also affected with marked basement membrane thickening in Bowman's capsule and glomerular capillaries; glomerulosclerosis and tubular changes were found in insulin-dependent disease. No evidence of diabetic retinopathy was found, and there was a high incidence of cataract.

Animals↗

Morphological changes in the endocrine pancreas of mice after treatment with streptozotocin combined with cyclophosphamide and neurotropin.

The effect of neurotropin (NSP) in combination with streptozotocin (STZ) and cyclophosphamide (CY) on blood glucose and pancreatic histopathology on day 7 and day 14 after the initiation of the treatment was studied in C57Bl/6 male mice. STZ (40 mg/kg) and NSP (1 mg/kg) were applied intraperitoneally on five consecutive days and CY (150 mg/kg)--twice on day 1 and day 3. In single B cells dilatation of the endoplasmic reticulum was found. On day 7 in proximity to some endocrine cells in the mice treated with STZ, STZ + CY + NSP and STZ + CY macrophages were observed. On day 14 lymphocytic infiltration of the islets was demonstrated only in the groups of mice injected with STZ, STZ + CY while in the group treated with the combination STZ + CY + NSP no infiltration was seen. All experimental groups showed no biochemical evidence for hyperglycemia probably due to the mild destruction of a small number of B cells. The results indicate that NSP might possess a restorative action on insulitis induced by multiple low dose streptozotocin administration in mice.

Animals↗

[Lymphoid cell infiltration into the pancreas of C57BL/6J mice].

Peri-insular lymphoid infiltrations were observed in nondiabetic C57BL/6J mice. The type of infiltrating cells was determined by direct immunoperoxidase technique. A larger part of lymphoid cells did not show reaction with a goat antimouse IgG Rh conjugate. Intensive hyperplastic reaction and the presence of many immunoglobulin producing cells were observed in the lymph nodes adjoining the pancreas. Probably the observed infiltrations in the pancreas of nondiabetic C57BL + 6J mice were composed mainly of T lymphocytes, belonging to T helper subpopulation.

Animals↗

Study of innervation of the pancreatic duct of Lepus europaeus, using the cholinesterase technique.

The innervation of the pancreatic duct was studied in the European Hare (Lepus europaeus) by the cholinesterase technique. The duct was accompanied by thick myelinated and thin non-myelinated nerve fibres, which subsequently formed a plexi. The plexi were associated with the fibres of the plexi of the islet of Langerhans, or with ganglia, blood vessels or neural networks. No chain of ganglia was observed on or near the duct and the ductules.

Acetylcholinesterase↗

[Changes in the rat endocrine pancreas under the effect of urbazon].

Hypertrophy and hyperplasia of islet tissue, established by morphometry, were proved in the pancreas of rats, treated chronically for a period of 2 months (with urbason-50 mg/kg of body mass). B-cells were granulated. Structures with myelin-like form of membranes were observed in some of them by electron microscope. Mixed islet B-acinar cells were established as well. These data were possibly a morphological expression of stimulating action of urbason on B-cells of Langerhans islets.

Animals↗