Ultrastructural manifestation of compensatory and destructive processes of the cell surface of endotheliocytes in trauma of the skeletal muscle

In trauma of the skeletal muscle the activation of the cell surface of endotheliocytes acquires a pathological pattern. Enhanced microvilli formation and clasmatosis lead to the formation of free emboli, which results in complete occlusion of the lumen of some vessels. Enhanced formation of microvilli leads to depletion of endotheliocytes, formation of transcellular channels, and necrosis of the vascular wall. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 8, pp. 212–216, August, 1994     

Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139

LY-450139 is a gamma-secretase inhibitor shown to have efficacy in multiple cellular and animal models. Paradoxically, robust elevations of plasma amyloid-beta (Abeta) have been reported in dogs and humans after administration of subefficacious doses. The present study sought to further evaluate Abeta responses to LY-450139 in the guinea pig, a nontransgenic model that has an Abeta sequence identical to that of human. Male guinea pigs were treated with LY-450139 (0.2-60 mg/kg), and brain, cerebrospinal fluid, and plasma Abeta levels were characterized at 1, 3, 6, 9, and 14 h postdose. Low doses significantly elevated plasma Abeta levels at early time points, with return to baseline within hours. Higher doses inhibited Abeta levels in all compartments at early time points, but elevated plasma Abeta levels at later time points. To determine whether this phenomenon occurs under steady-state drug exposure, guinea pigs were implanted with subcutaneous minipumps delivering LY-450139 (0.3-30 mg/kg/day) for 5 days. Plasma Abeta was significantly inhibited at 10-30 mg/kg/day, but significantly elevated at 1 mg/kg/day. To further understand the mechanism of Abeta elevation by LY-450139, H4 cells overexpressing the Swedish mutant of amyloid-precursor protein and a mouse embryonic stem cell-derived neuronal cell line were studied. In both cellular models, elevated levels of secreted Abeta were observed at subefficacious concentrations, whereas dose-responsive inhibition was observed at higher concentrations. These results suggest that LY-450139 modulates the gamma-secretase complex, eliciting Abeta lowering at high concentrations but Abeta elevation at low concentrations.     

Pattern of hyperlipidemia in rats with chronic renal failure

The character of the hyperlipidemia was studied in rats with chronic uremia caused by removal of five-sixths of the total weight of kidney tissue. The blood cholesterol and phospholipid concentrations were almost twice the normal level 13–30 days after subtotal nephrectomy in the rats with uremia. The hyperlipidemia was more marked when the blood nonprotein nitrogen level was high. The serum triglyceride concentration was not increased. The total concentration of serum -and pre--lipoproteins, determined nephelometrically, was significantly increased only if the nonprotein nitrogen exceeded 80 mg%. Disk electrophoresis of the serum lipoproteins of the rats with uremia revealed a definite increase in the -lipoprotein concentration and a very small increase in the -lipoprotein concentration. Postheparin plasma lipolytic activity in the rats with uremia was normal. Massive proteinuria was observed in the experimental rats, but the hypoproteinemia was not significant.Nephrology Problem Laboratory, I. M. Sechenov First Moscow Medical Institute. Pathomorphological Laboratory, Institute of Nutrition, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. M. Tareev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 6, pp. 676–679, June, 1978.     

The bovine rod outer segment guanylate cyclase,ROS-GC,is present in both outer segment and synaptic layers of the retina

Cyclic-GMP, which plays a pivotal role in visual transduction in the vertebrate retina, is synthesized by guanylate cyclase. The purpose of this study was to localize a rod outer segment-derived particulate guanylate cyclase (ROS-GC) to the retina of several species that have different populations of rods and cones. A rabbit antibody was raised against a synthetic peptide, corresponding to the sequence A107-L125 of bovine ROS-GC. Western blot analysis showed a single immunoreactive band at about 115 kDa with bovine rod outer segments but not with human rod outer segments. Light microscopic immunocytochemistry of tissue sections revealed immunoreactivity in the outer segment layer and in the outer and inner plexiform layers. The rod-rich rat retina showed uniform immunolabeling of outer segments; the cone-containing cat retina showed heavily labeled cone outer segments and lighter labeling of rod outer segments; the cone-rich chicken retina showed a uniformly and intensely labeled outer segment layer. Preincubation of the primary antibody with the peptide completely blocked antibody binding. Electron microscopic immunocytochemistry of the cat retina confirmed the presence of guanylate cyclase in photoreceptor outer segments and demonstrated its association with disk and plasma membranes. These data support a concept in which guanylate cyclase is much more concentrated in the outer segments of cones than rods. The immunolabeling of the plexiform layers suggests that the particulate guanylate cyclase is not unique to the photoreceptor outer segments, and may also play a role in transduction processes of retinal synapses.     

Correction of hyperlipoproteinogenic microangiopathy and organ pathology with thymalin and leu-enkephalin in the early stages of atherogenesis

The effects of thymalin and leu-enkephalin on lipid peroxidation and microcirculatory disorders in the early stages of atherogenesis are compared. Correction of the generalized microcirculatory response to hyperlipoproteinemia with the peptides manifested itself in the regression of atherosclerotic lesions in the aorta and restoration of the morphofunctional state of the myocardium and liver. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 108–111, January, 1996     

Effect of an antioxidant of the 3-hydroxypyridine class on microcirculatory disturbances associated with experimental dyslipoproteinemia and its alimentary correction

Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR. Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR G. N. Kryzhanovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 3, pp. 234–237, March, 1990.     

Pathomorphological signs of damage to capillary endothelium in skeletal muscle after traumatic injury to or replantation of a limb

Several months after an extensive crush injury to or replantation of a limb in rats, capillary endotheliocytes of its skeletal muscle are seen to undergo ultrastructural changes of both “dark” and “light” types. Destructive/degenerative changes of the “light” type are accompanied by intracellular edema and cytoplasmic homogenization and can eventually result in monocellular colliquative necrosis. Changes of the “dark” type are characterized by signs of functional overstrain in the endotheliocytes, succeeded by destructive/degenerative cytoplasmic changes, increased electron density of intracellular organelles, loss of distinct boundaries by the nucleus and intracellular structures, rupture of cell membranes, endothelial desquamation, and some other changes, which eventually lead to coagulation necrosis, followed by breakdown of the cell into small fragments. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N^no 10, pp. 378–383, October, 1994