Effects of cerebrocrast on local cerebral circulation and EEG in cats with cerebral hemorrhage]

In experiments on awake cats before and after intracerebral hemorrhage influence of cerebrocrast and nimodipine intravenous infusion (1 microgram/kg-1/min-1 during 60 min) on cerebral blood flow (CBF) in the cortex, thalamus and reticular formation and power of (alpha + beta)-, theta-, and delta-waves was investigated. During cerebrocrast infusion increasing CBF and improving bioelectrical activity were demonstrated.     

Synthesis and comparative evaluation of 4-oxa- and 4-aza-podophyllotoxins as antiproliferative microtubule destabilizing agents

A series of novel 4-oxa-podophyllotoxin derivatives 7 featuring the intact lactone ring D and various substituents in rings B and E has been synthesized and evaluated in a phenotypic sea urchin embryo assay along with the representative 4-aza-analogs 5 for their antimitotic and microtubule destabilizing activity. The most active compounds exhibited myristicin-derived or a 3',5'-dimethoxy substitution pattern in the ring E and a 6-methoxy moiety replacing the methylenedioxy ring A. Compounds 5xb, 5xe, 5yb, 7xa, 7xb, and 7xc showed potent antiproliferative effects in the NCI60 cytotoxicity screen. Notably, growth of the multi-drug resistant NCI/ADR-RES cells was more affected by these agents than the parent OVCAR-8 cell line. Although generally 4-oxa-podophyllotoxins were less potent than the respective 4-aza-derivatives in these assays, stability of the former series towards oxidation may prove to be of interest for the development of anticancer agents with in vivo activity.     

T cell proliferation induced by autologous non-T cells is a response to apoptotic cells processed by dendritic cells

Self-reactive T cells are present in the mature immune repertoire as demonstrated by T cell proliferation induced by autologous non-T cells in the autologous mixed lymphocyte reaction. This reaction generates regulatory T cells in vitro and may reflect immune regulatory pathways in vivo, but the antigenic peptides recognized remain uncharacterized. We revisited this issue in light of the importance of apoptosis in immune regulation. We found that apoptosis among peripheral blood non-T stimulator cells is associated with augmented induction of autologous T cell proliferation. Our data show that caspase activity in the non-T stimulator population is essential for induction of autologous T cell proliferation, suggesting that cellular components in the non-T cell fraction are enzymatically modified, most likely by effector caspases, and have a direct or indirect effect on autoreactive T cell activation. Furthermore, exposure of macrophage-derived dendritic cells to apoptotic non-T cells augments autologous T cell proliferation, and blockade of alpha(v)beta(5) integrin, but not alpha(v)beta(3), inhibits the capacity of irradiated non-T cells or dendritic cells to stimulate autologous T cell proliferation. These experiments, using an entirely autologous system, suggest the interpretation that autoreactive T cells may recognize self-Ags modified through the actions of caspases and presented to T cells by dendritic cells. Induction of an in vivo autologous mixed lymphocyte reaction by caspase-modified self-Ags present in apoptotic cells may represent a mechanism to maintain peripheral immune tolerance.     

Antidromic indentification of hypothalamic neurosecretory cells in rats

Characteristics of antidromic action potentials of neurons of the paraventricular and supraoptic nuclei of the rat hypothalamus were studied during stimulation of the hypothalamo-hypophyseal tract by stimuli of varied amplitude and frequency. Step-like changes were found in spike latency in response to an increase in strength (up to 1.5–2.5 thresholds) or frequency (over 100 Hz) of stimulation, as well as cases with variation of the degree of division of the peak into A and B components. Injection of leu-enkephalin analog into the third ventricle or intravenous injection of NaCl solution (1 M) caused reversible changes in the level of excitability of antidromically activated neurons: leu-enkephalin mainly increased the latent period and threshold of action potential generation and reduced the reproducible frequency of stimulation to 10 Hz, whereas NaCl had the opposite effect. The results indicate that when the adopted criteria of antidromic identification of neurosecretory cells are used the level of their excitability must be taken into account.A. A. Ukhtomskii Physiological Research Institute, A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 14, No. 6, pp. 585–591, November–December, 1982.     

Structural changes in membrane lipids of the sarcoplasmic reticulum of skeletal muscles during hypercholesterolemia

Membrane lipid phase has been studied in the sarcoplasmic reticulum (SR) of skeletal muscles, using spin probes. Hypercholesterolemia was found to increase rotation and decrease hydrophobicity of water-soluble probe medium located inside SR vesicles. This is probably indicative of the reduction in SR vesicle membranes. At the same time reduced rotation and increased hydrophobicity and regularity of fat-acid probe micro-environment are observed in hypercholesterolemia, with the differences disappearing nearer to the centre of the membrane. It is suggested that POL activation and cholesterol accumulation in SR membranes in hypercholesterolemia lead to greater density of phospholipid molecules in the membrane.