PADMA-28, a traditional tibetan herbal preparation inhibits the respiratory burst in human neutrophils, the killing of epithelial cells by mixtures of oxidants and pro-inflammatory agonists and peroxidation of lipids.

Both aqueous and methanolic fractions derived from the Tibetan preparation PADMA-28 (a mixture of 22 plants) used as an anti-atherosclerotic agent, and which is non-cytolytic to a variety of mammalian cells, were found to strongly inhibit (1) the killing of epithelial cells in culture induced by 'cocktails' comprising oxidants, membrane perforating agents and proteinases; (2) the generation of luminol-dependent chemiluminescence in human neutrophils stimulated by opsonized bacteria; (3) the peroxidation of intralipid (a preparation rich in phopholipids) induced in the presence of copper; and (4) the activity of neutrophil elastase. It is proposed that PADMA-28 might prove beneficial for the prevention of cell damage induced by synergism among pro-inflammatory agonists which is central in the initiation of tissue destruction in inflammatory and infectious conditions.

Physiochemical characterization of cardiovascular calcified deposits. I. Isolation, purification and instrumental analysis.

Calcified human aortic atherosclerotic deposits and calf ventricular assist device bioprosthetic deposits were isolated and deproteinated by hydrazine treatment. Detailed chemical and instrumental analyses were applied to gain comprehensive physicochemical information which makes possible establishing compositional and structural similarities between the 2 types of pathologic mineral deposits which form on different host surfaces. These microcrystalline deposit materials are morphologically very heterogeneous and can be represented chemically as carbonate substituted apatite which, in some of its properties, significantly differs from hydroxyapatite. It is indicated that the mechanism for the formation of cardiovascular deposits proceeds through hydrolysis of octacalcium phosphate precursor.

Persistence of staphylococcal cell-wall components in inflammatory sites may be due to the modulation by sulphated polyelectrolytes of autolytic wall enzymes: a working hypothesis.

The interaction of leucocytes with Staphylococcus aureus results in killing of the bacterial cells, but large portions of the bacterial cell walls persist apparently phagocytic cells for long periods. The mechanisms of biodegradation of staphylococci by leucocyte factors have shown that degradation of cell walls in vitro may be the result of the activation, by leucocyte kationic proteins, of the bacterial autolytic wall enzymes that are responsible for degrading the cell walls from within. This process is markedly inhibited by sulphated polysaccharides like dextran sulphate, by heparin, or by polyanetholesulfonate (liquoid). These anionic polyelectrolytes have also been shown to inhibit the lysis of staphylococci treated with bacteriolytic concentrations of penicillin G. Staphylococci injected intraarticularly into the knee joint of rats underwent massive plasmolysis, but structures compatible with cell walls (peptidoglycan) persisted within macrophages in the inflammatory sites, for long periods. It is postulated that the inability of leucocytes to degrade staphylococcal cell-wall components may be the result of the interference, by anionic polyelectrolytes likely to accumulate in the inflammatory sites, with the activation of the autolytic systems. Alternatively, anionic polyelectrolytes may coat the bacterial cells and interfere with the binding of the autolytic enzymes with their corresponding substrates.

Metabolic factors and preference for ethanol.

Alcohol intoxication diminishes the metabolic differences between ethanol- and water-preferring rats in the levels of free amino acids (liver, brain, blood plasma), lipid fractions (liver), the activities of glucokinase (liver), and aldehyde dehydrogenase (brain), and the content of glucose-6-phosphate and prostaglandins (liver). The action of alcohol is discussed as that directed to the partial elimination of biochemical individuality, thus simplifying the regulation of metabolism in the living system. In this connection preferential ethanol consumption may be regarded as a biological mode of self-correction.

Metabolic comfort and motivation of preference for ethanol.

Rats with preference for ethanol or water were selected by the method based on the minimal contact of the animals with the tested fluids (selection was made twice for 48 hours at two-week intervals). Over four days the selected groups of animals were given 5% (v/v) ethanol as their only source of fluid. The amount of some lipid fractions in various tissues and 14C-acetate incorporation into them were measured. The levels of free amino acids and their derivatives were studied in liver, blood plasma and urine. Twenty-four hours before sacrifice, ethanol was replaced by water. The animals with preference for water or ethanol were distinguished by content of various amino acids, lipid fractions and incorporation of 14C-acetate into the latter. The differences disappeared after ingestion of small amounts of ethanol. The data obtained indicate that preference for ethanol may be regarded as a mode of optimization of metabolic self-control in the organism.

Monoamine oxidase and the enzymes of ethanol metabolism in rats after administration of tetrahydroisoquinolines.

A mixture of tetrahydroisoquinolines, synthesized by the method of Osswald et al. (1975), was injected intraperitoneally at a dose of 2 mg/kg into rats. After 3 hours, the activity of ethanol-metabolizing enzymes (alcohol dehydrogenase and the microsomal ethanol oxidizing system) and acetaldehyde-metabolizing enzymes (NAD- and NADP-dependent aldehyde dehydrogenases) in liver sub-cellular fractions, as well as the activity of monoamine oxidase with noradrenaline, tyyramine, benzylamine and serotonin as substrates, were investigated in various brain areas. There was observed a decrease in the activity of the microsomal ethanol-oxidizing system and the NAD-dependent mitochondrial aldehyde dehydrogenase with low Km for acetaldehyde, the activity of the other enzymes investigated being invariable. The inhibition of the activity of monoamine oxidase with noradrenaline as a substrate was revealed in the caudate nucleus, cerebellum, truncus cerebri, and cerebral cortex, while only in the cerebral cortex was there revealed an inhibition of monoamine oxidase with the other substrates. The data obtained indicate that tetrahydroisoquinoline alkaloids not only disturb biogenic amine metabolism, but also affect ethanol and acetaldehyde metabolism in animals.

[Free amino acid content of tissues of rats which prefer either water or ethanol solutions]. / Soderzhanie svobodnykh aminokislot v tkaniakh krys, predpochtitel'no potrebliaiushchikh vody ili rastovor etanola.

The content of free amino acids is determined in tissue of rats which prefer either water or 5% water solution of ethanol. The rats which prefer ethanol have a higher content of taurine, threonine and urea in the liver, a larger amount of lysine and beta-aminobutyrate in the brain, less of ornithine in blood plasm and a larger amount of taurine, aspartate and urea in urine. Significant differences are supposed to be in the amino acids metabolism in rats which prefer either water or ethanol.