Role of FGF1, FGF2 and FGF7 in the development of the pancreas from control and streptozotocin-treated hamsters.

Although progress has been made with respect to the growth and transcription factors implicated in pancreatic development, many questions remain unsolved. It has been established that during embryonic life, both endocrine and acinar cells are derived from pancreatic epithelial precursor cells. Growth factors control the proliferation of precursor cells and their ability to differentiate into mature cells, both in pre-natal and in early post-natal life. Pancreatic development during the early post-natal period is an area of great interest for many scientists. In this study we have examined the structure characteristics, functional and proliferative activity of control and diabetic hamster pancreatic ductal, exocrine and beta cells, following treatment with FGFs 1, 2 and 7 in vitro. Light and electron microscopic studies indicated active synthetic processes in these cells under the influence of the investigated FGFs. In our experimental model of diabetes, the labelling index of the cells was significantly higher than in corresponding control groups of hamsters. We established that FGF2 at a concentration of 10 ng/l was responsible for the most prominent effect on ductal cells and beta cells in the diabetic groups. FGF1 at a concentration of 10 ng/l displayed the highest stimulatory effect on exocrine cells in the diabetic groups at post-natal day 10. Taken together these data strongly suggest that FGF1 and FGF2 induce proliferation of pancreatic epithelial cells during the early post-natal period whereas FGF7 is not strictly specific for pancreatic cell proliferation.

Effect of long-term treatment with a purified micronized flavonoid fraction on pancreatic mononuclear cell infiltration in diabetic BB rats.

Bio Breeding (BB) rats develop a genetically determined insulin-dependent diabetes, because of the early destruction of pancreatic beta cells of Langerhans islets, massively infiltrated by inflammatory mononuclear cells. S 5682, registered as Daflon, 500 mg, is a purified micronized flavonoid fraction (90% diosmin, 10% hesperidin), which has been shown to possess antiinflammatory properties, including anti-free radical activity, effects on vascular permeability, venous tone, and perivenous inflammation. We studied the effect of S 5682 on the course of pancreatic insulitis in diabetic BB rats. All the diabetic BB rats were hyperglycemic, with an increase of plasma levels of fructosamine, alpha-1 acid glycoprotein, and fibrinogen, and a dramatic decrease of C-peptide level. These parameters were not modified by S 5682. Pancreas histologic studies showed that in S 5682-treated diabetic BB rats, lymphocytic infiltration of Langerhans islets was less important and frequent than in untreated diabetic BB rats. By quantitative analysis, a highly significant difference was observed for insulitis, as well as perivasculitis, between S 5682-treated and untreated diabetic BB rats. This inhibitory effect of S 5682 on pancreatic mononuclear cell infiltration may be useful for a complementary treatment to decrease the development of insulitis in human insulin-dependent diabetes mellitus.

Changes in pancreatic islets in aging Wistar and Zucker rats: a histochemical and ultrastructural morphometric study.

Morphometrical and cytochemical techniques have been applied to characterize the islets of Langerhans tissue in lean and obese Zucker fa/fa and Wistar rats. The changes in cytologic composition correlated with levels of serum glucose and lipids in obese rats and progressed significantly with increasing body weight. Histochemical and enzyme abnormalities observed in Zucker fa/fa and Wistar rats reflect the degenerative and reactive processes in the pancreas: a decrease in Krebs cycle and pentose pathway and increased lysosomal acid phosphatase reflect the degeneration of the islets. Changes consisted of pronounced insulin cell hyperplasia and disruption of islet architecture. The raised functional activity in the islet B-cells of the Zucker fa/fa and Wistar rats was reflected in enlargement and fragmentation of the Golgi apparatus. An increased proportion of light granules is associated with increased insulin secretion, which reinforces the idea that light granules are responsible for immediate insulin secretion, whereas the dark granules represent the insulin stored in the cell for a longer period The islets of Langerhans of the Zucker fa/fa and Wistar rats show marked differences in morphological, histochemical and morphometrical characteristics when compared with littermates. There is a marked difference in insulin secretion between the obese Zucker fa/fa and Wistar rats and its non-obese littermate. These differences may be related to the development with obesity of aging and genetically-conditioned animals.

Relation between pancreatic islet cellular infiltration and plasma fibrinogen or alpha 1-acid glycoprotein levels in spontaneously and streptozotocin-diabetic rats: an increase in these protein levels is not necessary for inducing microcirculatory erythrocyte velocity alteration.

Plasma levels of fibrinogen, alpha 1-acid glycoprotein (AG) and albumin, pancreatic insulitis quantitative scores, and erythrocyte velocity in the mesoappendix microvessels were measured in BB diabetic (BBD) and streptozotocin-diabetic rats (WSTZ) in order to answer the following questions: (a) Does hyperfibrinogenemia or increase in AG plasma level occur in BBD and WSTZ rats, and if so, are these alterations secondary to the hyperglycemia or to an inflammatory process such as insulitis? (b) Is there a decrease in microcirculatory flow in the BBD and WSTZ rats, and if so, is it secondary to the hyperfibrinogenemia and/or the hyperglycemia? Insulitis was present in the BBD rats after 5 weeks of disease (with a score of 2.9 +/- 0.1 vs. 1.4 +/- 0.6 in the normoglycemic controls), but absent in WSTZ rats after 5 months of disease (1.2 +/- 0.06 vs. 1.1 +/- 0.06). Increase in fibrinogen and AG plasma levels was observed in the BBD rats only and appears linked to the insulitis. The major acute phase protein AG level is increased in BBD rats already on the first day of appearance of glycosuria. In the WSTZ rats, without insulitis, chronic hyperglycemia alone did not induce an increase in fibrinogen and AG plasma levels. A decreased microcirculatory erythrocyte velocity has been found in both BBD and WSTZ rats. Thus an increase in fibrinogen or AG plasma levels is not necessary for inducing a decrease in erythrocyte velocity. Hyperglycemia is probably the main factor responsible for the decrease in microcirculatory flow in the BBD and WSTZ rats.

[The ultrastructural changes occurring in the endometrium of women who use intrauterine pessaries]. / Ultrastrukturni izmeneniia, nastupili v endometriuma na matkata pri zheni, koito upotrebiavat vutrematochni pesari.

The authors studied ultrastructural changes in the endometrium of 25 women, using intrauterine contraceptive devices, preventing conception, during various time limits. The material of the endometrial biopsy was fixed with glutar and osmium in a phosphate buffer and embedded in durcopan. Section were prepared by a microtome and observed under electron microscope of Hitachi type. Comparing the parameters duration of usage of loops and character of changes in the endometrium an impression was obtained that the usage of contraceptive intrauterine devices for one-year period did not induced changes of pathological character. Functional changes in the endometrium occurred after a two-year stay of the loop in the uterus as there were inflammatory changes of spot-like character in two of the sections. Local areas of inflammation of nonspecific character, manifested under the form of lymphocytes and leucocyte accumulation, were found in women with long usage of contraceptive intrauterine devices. The authors advise to remove the loop 2.5-3 years after its application and to wait for the complete regeneration of the endometrium.

PIP: The results of electron microscope study of biopsy specimens of the endometrium from 25 women using the IUD are presented. Normal endometrium was characterized by the presence of 2 cell types (round and slightly elongated), complex system of plasma membrane invaginations, round cell nuclei, and moderately developed endoplasmic reticulum. Ultrastructural changes in the endometrium depended upon duration of IUD use. The use of IUD of up to 1 year (8 women) did not result in pathological changes in the endometrium. Of 25 women, 17 who used the IUD for 2-3 years showed various pathological and functional changes in the endometrium. The changes included destruction of mitochondria, formation of myelin-like degenerative structures, disintegration of the mitochondrial matrix, elongation of cell nuclei and appearance of invaginations in the nuclear membrane, increase in the size of plasma membrane, formation of low-density vesicles, presence of structures containing membrane fragments and vesicle-like inclusions resembling phagolysosomes, and extracellular growth of collagen tissue.

Effects of cyclosporin A on the endocrine pancreas of the rat. Morphological and immunohistochemical studies.

Treatment with the immunosuppressive agent cyclosporin A frequently gives rise to functional alteration of the islets of Langerhans which may result in diabetes. Light microscopy, immunocytochemical, and electron microscopy investigations demonstrate degranulation, vacuolization, and destruction of endocrine pancreatic cells in treated animals. Similar changes, but of a milder degree, are observed in the A-cells. The morphological alterations described are likely to be the result of inhibition of synthesis and secretion in B-cells.

Morphological changes in pancreatic B-cells after intravenous administration of forskolin.

The morphological changes in rat pancreatic islets were studied after intravenous injection of forskolin (1.5 mg/kg), an activator of adenylate cyclase, to male Wistar rats. A high amount of insulin containing granules was observed on PAP immunostained paraffin sections. Ultrastructural study of islet B-cells demonstrated enlarged perinuclear space, dilated cisternae of rough endoplasmic reticulum and activated Golgi complex with numerous vesicles. The results suggest that intravenous administration of forskolin produces a modest increase of B-cell synthetic activity in the pancreatic islets of rats. It is assumed that forskolin affects pancreatic B-cells via increased cAMP.

Immunohistochemical and electron microscopic changes in the endocrine pancreas after thymectomy.

This study showed that six months after adult thymectomy blood glucose level in rats was significantly lower compared to that of control animals. The low glucose level found in thymectomized rats was accompanied by structural changes in the pancreatic islets. Electron microscopy and paraldehyde fuchsin (PAF) stained paraffin sections revealed partial degranulation of B-cells.

[Protein composition and synthesis in islands of Langerhans isolated from normal rats and rats with alloxan diabetes]. / Kharakteristika belkovogo sostava i sintez belka v izolirovannykh ostrovkakh Langergansa podzheludochnoi zhelezy krys v norme i pri alloksanovom diabete.

Protein fractions with dissimilar electrophoretic mobility were identified in Langerhans, islands. In solitory islands, isolated from pancreas of rats with alloxan diabetes as compared with normal rats the protein composition varied distinctly: fractions of "constant" proteins and, specifically, the insulin fraction disappeared completely, total amount of identified fractions was decreased with relative alteration in their mobility. The total protein-synthesizing activity of Langerhans' islands from diabetic animals was 3-4-fold decreased as compared with that of control animals. An effect of "glucose repression" of protein synthesis was observed in isolated Langerhans' islands.

[The effect of rastinon on the beta cells of the rat and guinea pig pancreas]. / Efekt na rastinona vurkhu B-kletkite na pankreasa na plukha i morskoto svinche

Investigations are carried out with light and electron microsckope on the islands of Langerhans in rats and guinea pigs following Rastinon treatment over variable time intervals. The beta cells were strongly activied: with expanded ergastoplasm (archiplasm), enlarged and elongated mitochondria, Golgi's complex of a multiple vesiculose type, abudance of coated vesicles, marginization of secreting B-granules along the cellular membranes and perforated sacs. In addition, mixed island-acinous cells and bright degranulated and agranulated cells, which represent beta cells in different phases of insulin secretion, were observed. The bright agranulated cells are assumed as demontrating a refrangible recovery phase of the beta cells.