The ionic basis of the membrane potential in a rat glial cell line.

Intracellular ionic concentrations, membrane potential and Na+ and K+ flux were measured in a clonal rat glial cell line, C6. Intracellular concentrations of C6 cells were: (mmole/liter cell water) K+ 145 +/- 4 S.D., Na+ 18 +/- 4 S.D., Cl- 14 +/- 1 S.D. Cells maintained a steady state level of K+ over the duration of the experiments. This was substantiated by the close agreement between absolute values for K+ influx and efflux measured with 42K. When cells were depleted of internal Na+, K+ influx was significantly reduced suggesting that a portion of inward K+ movement is linked to Na+ extrusion. Efflux of Na+, calculated from the half-time of exchange from cells preloaded with 22Na, was higher than passive Na+ influx determined by blocking Na+ extrusion with ouabain. Since cell Na+ concentration remained relatively constant, part of the Na+ efflux may be due to exchange diffusion. The average membrane potential of C6 cells uas -36 mV. The potential showed a 31 mV slope for a 10-fold change in external K+ so that it is determined predominantly by the ratio of external/internal K+. The potential however, consistent with the relatively large passive Na+ influx, was influenced by Na+. Replacing all but 20 mM external Na+ with choline hyperpolarized the membrane by 13 mV. The ratio of PNa/PK of 0.11 suggests that Na+ is outwardly transported to maintain the steady-state concentrations observed. Since these responses are similar to those in non-tumor glia, it suggests that the C6 cell line may provide a useful model for studying ionic regulation in glial cells.     

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Coronary reserve and differentiated therapy of its disorder]

The clinical course of the ischaemic heart disease was studied and compared with the ECG indices at rest, and under exercises, and with the data of selective coronary angiography in 189 patients. Three stages of decompensation of the coronary reserve were revealed. The efficiency of drug therapy and the indications for surgical management were studied with reference to the state of the coronary reserve.     

Tumor necrosis factor-alpha downregulates protein S secretion in human microvascular and umbilical vein endothelial cells but not in the HepG- 2 hepatoma cell line

Protein S deficiency, which is associated with thrombosis, can either be inherited or acquired. Recently, we reported that a decrease in free protein S was observed in 19 of 25 persons with HIV/AIDS. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been reported to be elevated in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and has been shown to induce a procoagulant state on the surface of endothelial cells. We report here that recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the SV-40T transfected human microvascular endothelial cell line (HMEC-1) model system by approximately 70% and in primary human umbilical vein and dermal microvascular endothelial cell cultures by approximately 50%. Using the HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at 24 hours that was corroborated by Western blot analysis and enzyme- linked immunosorbent assay (ELISA) quantification. Evidence supporting the specificity of the TNF-alpha effect included the following: (1) TNF- alpha down-regulation of protein S was completely blocked by TNF neutralizing antibody; (2) the effect was transient, and protein S was restored to near normal levels after TNF was removed from cell cultures; (3) an antibody directed to the TNF RI (55-kD receptor) was shown to mimic the action of TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines, interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S secretion. However, TNF-alpha showed no regulatory control over protein S synthesis in the human hepatocellular carcinoma cell line HepG-2. We suggest that TNF-alpha downregulation of protein S may be a mechanism for localized procoagulant activity and thrombosis recently reported in some AIDS patients with associated protein S deficiency.     

Cerebral phosphorus metabolite abnormalities in opiate-dependent polydrug abusers in methadone maintenance

This study evaluated cerebral phosphorus metabolites in opiate-dependent polydrug abusers in methadone maintenance therapy (MMT) and determined whether metabolite profiles differed based on treatment duration. Phosphorus magnetic resonance spectroscopy (³¹P-MRS) data were acquired with the ISIS volume localization method from a 50-mm thick axial brain slice through the orbitofrontal and occipital cortices. Study subjects included 15 MMT subjects, seven having undergone treatment for an average of 39±23 weeks (mean±S.D.) and eight having undergone treatment for 137±53 weeks, as well as an age matched comparison group (n=16). The methadone dose administered on the study day averaged 70.5±17.1 mg and was statistically equivalent in short- and long-term subgroups. MMT subjects (n=15) differed from control subjects in percent phosphocreatine (%PCr) levels (−13%), and in both phosphomonoester (%PME, +13%) and phosphodiester (%PDE, +10%) levels, which likely reflect abnormalities in energy and phospholipid metabolism, respectively. There were no sex effects or group by sex interaction effects on these measures. In short-term MMT treatment subjects, abnormal %PCr (−18%), %PME (+20%) and %PDE (+17%) levels were found compared with control subjects. The only metabolite abnormality detected in long-term MMT subjects was decreased %PCr (−9%), in spite of continued illicit drug abuse. From these data, we conclude that polydrug abusers in MMT have ³¹P-MRS results consistent with abnormal brain metabolism and phospholipid balance. The nearly normal metabolite profile in long-term MMT subjects suggests that prolonged MMT may be associated with improved neurochemistry.