S. Syed Ali

Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats

SummaryWe have previously shown that long-term administration of aminoguanidine, an inhibitor of advanced glycosylation product formation, reduces the extent of experimental diabetic retinopathy in the rat by 85%. In order to determine whether the residual retinopathy that developed despite aminoguanidine was attributable to advanced glycation endproduct formation, a time-course study was performed in three different groups of male Wistar rats: non-diabetic controls (NC), streptozotocin-diabetic controls (DC) and streptozotocin-diabetic rats treated with aminoguanidine HCL, 50 mg/100 ml drinking water (D-AG). Eyes were obtained at 24, 32, 44 and 56 weeks of diabetes/treatment duration and morphologic evaluation was done on retinal digest preparations. At 56 weeks, retinal basement membrane thickness was additionally measured. After 24 weeks of diabetes, the number of acellular capillaries was significantly elevated in DC (44.6±5.7/mm2 of retinal area, NC 19.6±4.9; p<0.001) and increased continuously over time (DC 56 weeks 87.4±15.1; p<0.001 vs DC 24 weeks). In contrast, acellular capillaries in D-AG increased over the first 24 weeks and then remained constant for the rest of the study (D-AG 24 weeks 35.7±5.18; p<0.01 vs NC 24 weeks and NS vs DC 24 weeks; D-AG 56 weeks 42.0±6.20; p NS vs D-AG 24 weeks). Diabetes-associated pericyte loss (DC 24 weeks 2310±170/mm2 of capillary area; NC 24 weeks 3120±190; p<0.001; DC 56 weeks 1570±230; NC 56 weeks 2960±50; p<0.001) was significantly prevented by aminoguanidine after diabetic-like changes over the initial 24 weeks (D-AG 24 weeks 2450±75; p NS vs DC 24 weeks; D-AG 56 weeks 2350±90; p<0.001 vs DC 56 weeks). At 56 weeks, aminoguanidine treatment was associated with a 67.4% reduction in retinal basement membrane thickening. This time-course study demonstrates that aminoguanidine prevents the progression of experimental diabetic retinopathy, and suggests that non AG-inhibitable mechanisms are involved in the initial phase of diabetic retinopathy.

The Blood Supply of the Growth Plate and the Epiphysis: A Comparative Scanning Electron Microscopy and Histological Experimental Study in Growing Sheep

The blood supply of the growth plate has been described in the late 50s and early 60s, and there was controversial discussion about the existence of transphyseal vessels. The vascular supply of growth plate and epiphysis of the proximal tibia was reinvestigated using a modern technique, the Mercox-perfusion method, in six sheep aged 6-24 weeks. A comparison was made among pure perfusion specimens, the corrosion casts, and histological sections. The metaphyseal, epiphyseal, and perichondral blood supply systems were confirmed. However, there was evidence of regular transphyseal anastomoses between the metaphyseal and epiphyseal system. Based on the histological arrangement of the blood vessels, the arterial blood flow would appear to be from the metaphysis to the epiphysis. The existence of transphyseal arterial vessels originating metaphyseally and seen both in cast preparations and histological sections was added to the present description of the blood supply of the growth plate. Age-related differences in the vascularization of the growth plate were not found in this study.

Vascular pattern in the pancreas of the cat

SummaryThe pathways of microcirculation in the pancreas of the cat were investigated by scanning electron microscopy of Mercox preparations of the vascular bed. A portal system from islet to exocrine vessels as well as a direct arterial flow to the exocrine pancreas have been observed. Sphincters appear to exist in portal capillaries at the border between the endocrine and exocrine portions of the pancreas. Islets possess an independent venous drainage.

Microvasculature of the pineal organ of the rainbow trout (Salmo gairdneri)

SummaryThe angioarchitecture of the pineal organ of the rainbow trout (Salmo gairdneri) was investigated by means of the corrosion-cast preparation method and scanning electron microscopy. Two main arteries (aa. epiphyseales) supply the pineal parenchyma. They emerge from the aa. cerebri anteriores and run in the fissure between the prosencephalon and the mesencephalon. After entering the pineal stalk, the aa. epiphyseales branch off into several arterioles, most of which extend to the pineal end-vesicle where they give rise to a lobular, bilaterally symmetric capillary network. Capillaries establishing the main portion of the pineal vessels appear widened in comparison to those supplying other portions of the brain and resemble capillaries in other endocrine organs. In Salmo gairdneri, no specialized system of portal vessels appears to exist between the pineal organ and other portions of the brain.

Distribution and ultrastructure of somatostatin-immunoreactive cells in the pancreas of Rana esculenta.

Apart from a description of the general organization of the endocrine pancreas, the present study is focussed on the distribution and ultrastructural morphology of somatostatin-immunoreactive cells in the pancreas of the frog Rana esculenta. For light-microscopic histochemistry, the peroxidase-antiperoxidase technique was used. For the ultrastructural investigation, we employed the immunogold method. The endocrine pancreas of R. esculenta is composed of numerous islet-like structures, which contain several small somatostatin-immunoreactive cells arranged in the form of clusters. Often, however, single somatostatin cells are randomly distributed among the acinar tissue of the pancreas. These individually arranged elements possess long processes which terminate on exocrine pancreatic cells. The ultrastructural features of somatostatin-immunoreactive cells speak in favor of their endocrine and paracrine functions.

Kristallographische Interpretation der Feinstruktur der B-Granula in den Langerhansschen Inseln der Ringelnatter, Natrix n. natrix (L.)

SummaryCrystalline B-granules of grass-snake islets of Langerhans have been shown to possess the shape of rhombic dodecahedra (a ≈ 11 nm, cubic body-centered lattice). Three-dimensional reconstructions from serial sections, optical diffractometry and comparison with crystal models were the techniques utilized. The significance of crystalline B-granules is discussed.ZusammenfassungKristalline B-Granula im Pankreas der Ringelnatter besitzen die Form von Rhombendodekaedern (a ≈ 11 nm, kubisch-raumzentriertes Gitter). Diese Diagnose wird abgeleitet von den Ergebnissen der dreidimensionalen Rekonstruktion von Serienschnitten, der optischen Diffraktometrie und aus dem Vergleich mit Kristallmodellen. Die Bedeutung kristalliner B-Granula wird erörtert.Kristalline B-Granula im Pankreas der Ringelnatter besitzen die Form von Rhombendodekaedern (a ≈ 11 nm, kubisch-raumzentriertes Gitter). Diese Diagnose wird abgeleitet von den Ergebnissen der dreidimensionalen Rekonstruktion von Serienschnitten, der optischen Diffraktometrie und aus dem Vergleich mit Kristallmodellen. Die Bedeutung kristalliner B-Granula wird erortert.

Angioarchitecture of the pancreas of the cat

SummaryBy the use of scanningand transmission electron microscopy, the possible sources of errors in interpretation of the microcirculation of the pancreas can be reduced in comparison to the classical India-ink injection method. Sphincter-like structures in the capillary wall of the cat pancreas are established by pericytes. These sphincters encircle the junctional zones between the endocrine and exocrine capillaries. They are assumed to be regulatory structures of blood flow and to regulate indirectly hormone secretion according to demand.

Angioarchitecture in the heart of rats with streptozotozin-induced Diabetes mellitus

The effects of chronic streptozotozin-induced diabetes mellitus on the angioarchitecture of the heart in male Wistar rats were studied with the use of cast preparations and scanning electron microscopy. The following results were obtained in normal rats. Epicardial arteries branch obliquely and run parallel to the outer surface of the heart. Arterioles emerging from these arteries run in different directions. They show a fold-like structure equipped with a prearteriole sphincter. The capillaries in the myocardium form a net-like architecture with many H-like and Y-like anastomoses. Venous capillaries run directly into small veins at right angles while venules converge to form small veins at acute angles. In rats which have been suffering from diabetes mellitus for 8 months the capillary system appears less systematically arranged. The venous system generally exhibits dilatations. Dilatations were also seen along capillaries at short distances. In rats which had had untreated diabetes mellitus for 2 months and then 6 months of insulin treatment, a dilatation of the whole venous system was seen, but there were no significant changes in the capillary system.

Microangioarchitecture of the islets of Langerhans in the snakes,Naja naja, Vipera russelli, andEchis carinatus

SummaryDue to a decided lack in the literature of reports on the microangioarchitecture of the pancreas of snakes, an analysis was performed in three different species of two different ophidian families with the use of cast preparations and complementary scanning electron microscopy. The vascular architecture reflects the lobular substructure of the pancreas; the organ is supplied by branches of the superior mesentric artery. Coiled lobular arteries and arterioles continue into a meshwork of capillaries. Dilated capillaries of the endocrine portion of the pancreas are an integral component of this fine capillary network. A few very small capillaries establish a connection between the endocrine and the exocrine pancreas. The other capillaries drain into venules, which ultimately join their respective veins. No interspecific differences were noted in the vascularization of the pancreas of the three ophidian species examined. The present results suggest the existence of arterio-venous anastomoses and speak against the presence of a portal system, but establish a feed-forward capillary connection from the endocrine to the exocrine component of the ophidian pancreas.

Acute Generalized Exanthematous Pustulosis Induced by Erlotinib (Tarceva) with Superimposed Staphylococcus aureus Skin Infection in a Pancreatic Cancer Patient: A Case Report.

Acute generalized exanthematous pustulosis (AGEP) is a rare acute reaction that is drug induced in 90% of the cases and characterized by a widespread, sterile pustular rash. Erlotinib, a small-molecule EGFR tyrosine kinase inhibitor, has been approved by the FDA for patients with pancreatic cancer and non-small cell lung cancer. Skin rash is a well-known side effect related with all EGFR blocking agents. It has been suggested that rash could be used as a surrogate marker for response and possibly be associated with prolonged survival. We report a case of rare presentation of AGEP involving an adverse effect of erlotinib. The commonly reported adverse effects of erlotinib are mild skin eruptions. However, our case describes the rare presentation of AGEP induced by erlotinib. The estimated incidence rate of AGEP is approximately 1–5 cases per million/year.