Protective effect of glucan-enhanced macrophage function in experimental pancreatitis

In an effort to assess the impact of enhanced macrophage function in acute pancreatitis, mice were subjected to a choline-deficient diet supplemented by ethionine to induce necrotizing pancreatitis. Treatment with the macrophage stimulant glucan resulted in improved survival rates (58 percent versus 14 percent) and maintenance of pancreatic architecture. Glucan treatment also resulted in decreased plasma and peritoneal trypsin activity, as well as increased trypsin-binding activity in the blood and peritoneal cavity. Plasma interleukin-1, as well as macrophage production of interleukin-1, were increased in the glucan-treated mice, which indicated enhanced macrophage function. These composite findings suggest that by enhancing diverse aspects of reticuloendothelial function, clinical use of immunomodulators may have significant impact on the pathogenesis of acute pancreatitis.     

A comparison of the actions of pentobarbitone and etomidate on [H]GABA binding to crude synaptosomal rat brain membranes

A study was performed in which both anterograde ([³H]leucine radioautography) and retrograde (horseradish peroxidase (HRP) histochemistry) tracing methods were employed to identify the origin of the fimbrial projection to the nucleus accumbens in the rat. The data reveal that this pathway arises predominantly from layers II–III of the anterior two-thirds of entorhinal cortex rather than from any part of hippocampal formation.     

Immunochemotherapy of bladder carcinoma with glucan and cyclophosphamide

Recent evidence suggests a role for both immunotherapy and chemotherapy in the treatment of transitional cell carcinoma. Glucan, a derivative of the cell wall of Saccharomyces cerevisiae and a potent immunostimulant, was used in combination with cyclophosphamide for treatment of implanted murine transitional cell carcinoma (MBT 2). Cyclophosphamide prevented tumor appearance when tumor burden was low and decreased tumor growth rate in larger tumor volumes, but was unable to eradicate established tumors. Glucan did not reduce tumor incidence but decreased animal mortality. These experimental observations may correlate well with clinical evidence and suggest future clinical use of these agents.     

Contrasting effects of a convulsant (CHEB) and an anticonvulsant barbiturate (phenobarbitone) on amino acid release from rat brain slices

The effects of a convulsant barbiturate, 5(2-cyclohexylidine-ethyl)-5-ethyl barbituric acid (CHEB), and phenobarbitone (PhB) on the release of exogenous D-aspartate and GABA from slices of rat cerebral cortex were investigated. While PhB inhibited potassium-evoked release of D-aspartate more so than that of GABA, CHEB potently inhibited potassium-evoked GABA release and stimulated evoked D-aspartate release, in a concentration-dependent manner. These actions are consistent with the observed in vivo convulsant and anticonvulsant properties of these barbiturates. CHEB, but not PhB also elevated spontaneous efflux of both amino acids. The actions of these barbiturates were further studied in calcium- and sodium-free media, and in the presence of tetrodotoxin and ruthenium red, agents known to alter ion flux across neuronal membranes. The results obtained indicate that different ionic mechanisms may be involved in the release of excitatory and inhibitory amino acid transmitters.     

Voltage clamp analysis of the inhibitory actions of diphenylhydantoin and carbamazepine on voltage-sensitive sodium channels in neuroblastoma cells

The actions of diphenylhydantoin (DPH) and carbamazepine (CBZ) on sodium channels in mouse neuroblastoma cells (clone N18) were analyzed using the patch voltage clamp procedure in the whole cell configuration. DPH and CBZ reduced sodium currents without effect on the voltage dependence of sodium channel activation. Half-maximal inhibition was observed with approximately 30 microM of each drug. Depolarization increased and hyperpolarization reversed channel block by these two drugs in the voltage range from -90 to -45 mV. Repetitive stimulation at 2 Hz or greater enhanced inhibition of sodium channels. The half-time for recovery from voltage-dependent inhibition was greater for DPH (1.36 sec) than for CBZ (0.38 sec). A combination of prolonged depolarizing pulses of 15 mV with superimposed brief maximal depolarizations designed to mimic the electrical activity in an epileptic focus gave additive effects of voltage-dependent and frequency-dependent inhibition. The results support the previous proposal that DPH and CBZ are sodium channel-selective anticonvulsants and provide a potential basis for specific inhibition of neurons in epileptic foci. The mechanism of DPH and CBZ action is considered in terms of an allosteric or modulated receptor model of drug binding and action.     

Retinal benzodiazepine receptors are destroyed by kainic acid lesions

[3H]Diazepam binds to preparations of membranes from chicken retina. Two binding sites were detected; a high affinity site (KD, 1.8 nM and Bmax, 0.17 pmol/mg retina protein) and a low affinity site (KD, 132 nM and Bmax, 1.46 pmol/mg retinal protein). GABA stimulated [3H]diazepam binding to these retinal membranes. One week after injection of kainic acid into the eye, which destroys the horizontal and amacrine cells of the retina, the low affinity site disappeared, while the level of the high affinity site was hardly affected. These results establish that chicken retina contains benzodiazepine receptors, which are closely associated with GABA receptors. The benzodiazepine receptors are probably associated with horizontal and/or amacrine cell synapses which use GABA as a transmitter.     

Glucan-induced keratoderma in acquired immunodeficiency syndrome

Six of 20 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex receiving intravenous infusions of soluble glucan (beta-1-3 polyglucose) developed a keratoderma of the palms and soles. The eruption began during the first two weeks of therapy and resolved two to four weeks after its discontinuation. The eruption was different in appearance from our previously reported keratoderma blennorrhagica in AIDS-associated psoriasis. None of the other 735 patients with AIDS or AIDS-related complex not treated with soluble glucan developed a similar keratoderma. The correlation between receiving glucan and the hyperkeratosis is highly significant. Since glucan is a naturally occurring component of the cell walls of yeast, fungus, and some bacterial organisms, recognition of its ability to induce such a striking reaction pattern may be of general significance and interest, although the reaction itself may be limited to patients with AIDS.     

Dose-dependent effects of taurine on convulsions induced by hypoxia in the rat

Taurine and phenobarbitone had protective effects in hypoxia-induced convulsions in rats. The dose of taurine was found to be a critical factor. Thus, while 50 mg/kg of taurine was most effective in suppressing onset of convulsions, 100 mg/kg adversely affected its anticonvulsant action.