The effect of a mite allergen on Na/H metabolic activity in peritoneal mast cells]

Mite allergen interacting with mast cells treated with sera from bronchial patient sensitized to home dust Dermatophagoides farinae causes changes in intracellular pH. Regulation of pHi peritoneal mast cells is participated by Na/H metabolism probably activated by protein kinase C.     

The enzymatic chemical mechanisms of adaptation]

In sheep from biogeochemical provinces enriched by molybdenum and copper and in a model form of molybdenum toxicosis in animals, the important role of enzymic and neurohumoral systems in the development of adaptation to excessive uptake of molybdenum and copper has been demonstrated. Adaptive reorganization of the activity of enzymic systems (xanthine oxidase, ceruloplasmin, succinate dehydrogenase, aspartate and alanine aminotransferases) and gradual involvement of neurohumoral mechanisms of the sympathoadrenal and cholinoreactive systems provide for adaptation of some animals in molybdenum and copper-molybdenum biogeochemical provinces. In other sheep, under the same conditions, dystonic disturbances in the vegetative nervous systems are observed together with the development of molybdenum toxicosis.     

The immunochemical mechanisms of body adaptation to a chemical environment]

For the first time the dynamics of metabolic and immune responses to xenobiotics were analyzed in their long-term effect on the organism. It was shown that the organism gradually lost the capacity to respond to xenobiotics with the induction of hepatic cytochrome P450 and immune response. Possible mechanisms of this phenomenon are under consideration.     

内分泌干扰物中毒机理探析

叙述了内分泌干扰物(EDC)的类型及危害,讨论了活性氧在内分泌干扰物环境毒理学的相关定义,并进一步解释了活性氧所引起的中毒机理。     

A comparative study of the expediency of using different chemical methods for determining protein in allergen preparations]

Parallel use of some known chemical procedures for measurements of protein in commercial forms of allergens revealed considerable variations in the results, which was due to the nature of the methods used and to admixtures of different substances in the preparations under study. The conclusion on the necessity of using at least two methods of protein determination for the standardization of allergens was made. Preference was given to Bradford's method. As the standardization of allergens manufactured in the USSR is carried out on the basis of the quantitative determination of protein (in PNU), this problem is of not only theoretical, but also practical importance.     

Neurophysiological mechanisms of the antihypertensive effect of clopheline in pain]

In experiments on conscious and unanesthetized cats it was shown that clopheline in analgesic doses do not change the pain baroreflex blood pressure regulation and mild brain antinociceptive sympathoactivating influences. The clopheline antihypertensive effect was due to nonopiate direct sympathoinhibitory effect realized by suprasegmental level of vasomotor regulation.     

Understanding the chemical mechanisms of life

Understanding the biological, medical and ecological pathways of complex transformations will be greatly aided by the chemist's molecular approach. The 2nd European Conference on Chemistry for Life Sciences brought together these diverse disciplines to consider where we are and where we will go.     

Stress mechanisms and metabolic complications.

Stress can be defined as a state of threatened homeostasis or disharmony. An intricate repertoire of physiologic and behavioral responses is mobilized under stressful situations forming the adaptive stress response that aims to reestablish the challenged body equilibrium. The hypothalamic-pituitary-adrenal axis and the central and peripheral components of the autonomic nervous system constitute the two main pillars that subserve the vital functions of the stress system. Chronic stress represents a prolonged threat to homeostasis that can progressively lead to a deleterious overload with various complications caused by both the persistent stressor and the detrimental prolongation of the adaptive response. Recent data indicate that chronic stress is associated to derangement of metabolic homeostasis that contributes to the clinical presentation of visceral obesity, type 2 diabetes, atherosclerosis and metabolic syndrome. Notably, indices of stress in the modern western societies correlate with the increasing incidence of both obesity and the metabolic syndrome which have reached epidemic proportions over the past decades. The pathogenetic mechanisms that accommodate these correlations implicate primarily the chronic hyperactivation of the HPA axis under prolonged stress, which favors accumulation of visceral fat, and VICE VERSA; obesity constitutes a chronic stressful state that may cause HPA axis dysfunction. In addition, obesity is being now recognized as a systemic low grade inflammatory state that contributes to the derangement of the metabolic equilibrium, implicating the adipocyte secretion of adipokines to the pathogenesis of several components of the metabolic syndrome. Understanding the mechanisms that mediate the documented reciprocal relationships between stress and metabolic homeostasis will hopefully provide novel insights to the pathophysiology of obesity, type 2 diabetes, and their cardiometabolic complications, and will help the quest for more specific and effective therapeutic interventions.     

Histamine-liberating effect of antihistaminics on the isolated rat mast cells]

Research Allergological Laboratory of the USSR Academy of Medical Sciences and Laboratory of Pharmacology, S. Ordzhonikidze Research Chemico-Pharmaceutical Institute, Moscow. Among the tested new antihistaminic drugs (quinuclidine derivatives) quinuclidyl-3-(O-tolyl) carbinol possessed histamine releasing action (HRA) on the isolated rat mast cells. In used concentrations (up to 0.4 mmol) all phenothiazines (promethazine, phenethazine, chlorpromazine, methylene blue) had HRA. There was no correlation between the HRA and the antihistaminic activity of the tested drugs. Histamine release induced by antihistaminic drugs and a steep dose-response curve, was produced at low temperature and was not inhibited under conditions of inhibition of energy-dependent stage of 48/80-induced histamine release. It was concluded that the tested antihistaminic drugs which had HRA were non-selective histamine releasers.     

Increase in stability of isolated tissues and proteins caused by the action of chemical stimulants]

Chemical agents in subtoxic concentrations prolongate the survival time of living muscles and the time of contractile ability of glycerinated muscles. They preserve also the native property of actomyosine over the control time. The increase of resistance of living muscles and their models may be explained by stabilization of proteins or of their complexes. It is accompanied by the change of the indices of the functional state of the living muscle--by the decrease of the binding of vital dyes, by the hyperpolarization, by reducing the consumption of O2 and by the conservation of the quantity of SH groups at the high level.     

Analysis of the types of chromosome aberrations in the combined action of chemical mutagens]

Types of chromosome aberrations were studied in human lymphocyte cultures in combined action of different concentrations of thiophosphamide and dipine in different proportions. The mutagens acted at the Go stage. The range of the concentrations studied was from 3.17-10(-5) M to22.19-10(-5) M. As compared with dipine, the equimolar concentrations of thiophosphamide induced more chromatid exchanges and less sister (isolocus) unions, and also a greater part of single breaks and the part of breaks in the chromatid exchanges of the total number of chromosomal breaks. Both absolute and relative frequencies of chromosome aberrations depended on the mutagens concentration. A change of the thiophosphamide and dipine proportion with a constant total number of molecules of the two mutagens at different concentration levels led to the effect, the level of which was between the effect of action of equimolar concentrations of pure mutagens. This effect depended upon the part of each mutagen in combined treatment. A conclusion was drawn on the additivity of thiophosphamide and dipine action.     

Effect of chemical action on the biological activity of staphylococcal allergen

The authors present the results of study of chemical action on the specific properties of staphylococcus allergen showing that deamination, iodation, and formalinization was accompanied by reduction of the allergenic capacity of the preparation; as to acetylation -- it produced an insignificant reduction of the allergen activity.     

Study of metabolic activation of chemical compounds by using microorganisms. I. Effect of inducers of microsomal systems]

The effect of psychotropic drugs phenobarbital, benzonal, hexamidine and steroid hormone hydrocortizon acetate on the process of metabolic activation of mutagenicity of nitrosomorpholine, cyclophosphamide and benzidine was examines using tester strains TA 1950 and TA 1538 of Salmonella typhimurium (by B. N. Ames). The listed above activators did not modify essentially the mutagenic effect of benzidine. The mutagenic action of nitrosomorpholine was increased by the presence of hydrocortizon acetate. Psychotropic drugs phenobarbital and its structural analogues increased the mutagenic effect of cyclophosphamide and nitrosomorpholine. Phenobarbital was the most potent as an inducer. Benzonal occupied the intermediate position according to the including activity of mutagens examined. Phenobarbital has shown to increase both the content of rat liver microsomal proteins and the specific activity of those. A possible role of microsomal enzymatic inducers as modifiers of the effects of environmental mutagens is discussed.     

Study of the mechanisms of cytotoxic effect of uranyl nitrate

The mechanisms of cytotoxic effect of uranyl nitrate were studied. It was shown that uranyl nitrate induced HEp-2 cell death, mainly by necrotic way. In the experiments in vitro, uranyl nitrate caused an appearance of 8-oxoguanine in DNA, indicating the induction of oxidative stress. The experiments with isolated rat liver mitochondria revealed that 1 mM uranyl nitrate decreased the respiration rates of mitochondria in state 3 and DNP-induced respiration. At the same time, uranyl nitrate had no influence on the opening of the mitochondrial permeability transition pore and decreased the rate of formation of H₂O₂ by mitochondria. Possible molecular mechanisms of uranyl-induced necrosis are discussed.     

Biochemical and immunochemical analyses of the protein components of the cell wall in group-A streptococci isolated by a sparing chemical method]

To study the protein components of the cell wall of group A streptococci, type M 29, a special preparative method was developed (extraction with 1 M hydroxylamine solution, pH 6.0, and subsequent purification). Altogether six protein fractions were obtained. The isolated proteins were found to be a heterogeneous group of molecules, consisting of 25-40 individual proteins with molecular weights ranging between 13 and 94 kD. The study of the protein fractions thus obtained in the immunodiffusion test with rabbit antiserum to the initial protein preparation revealed that these proteins contained type-specific components, 3-6 type-nonspecific protein antigens common with protein antigens of M 1 and M 12, as well as one protein antigen common with type M 1. Fc receptor was shown to be absent. The detected type-nonspecific protein antigens were partially separated by ion-exchange chromatography and some of them could be purified from the admixtures of nucleic acids and group-specific polysaccharide.     

Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease

PURPOSE OF REVIEW: Adiponectin is secreted exclusively by adipocytes, aggregates in multimeric forms, and circulates at high concentrations in blood. This review summarizes recent studies highlighting cellular effects of adiponectin and its role in human lipid metabolism and atherosclerosis. RECENT FINDINGS: Adiponectin is an important autocrine/paracrine factor in adipose tissue that modulates differentiation of preadipocytes and favors formation of mature adipocytes. It also functions as an endocrine factor, influencing whole-body metabolism via effects on target organs. Adiponectin multimers exert differential biologic effects, with the high-molecular-weight multimer associated with favorable metabolic effects (i.e. greater insulin sensitivity, reduced visceral adipose mass, reduced plasma triglycerides, and increased HDL-cholesterol). Adiponectin influences plasma lipoprotein levels by altering the levels and activity of key enzymes (lipoprotein lipase and hepatic lipase) responsible for the catabolism of triglyceride-rich lipoproteins and HDL. It thus influences atherosclerosis by affecting the balance of atherogenic and antiatherogenic lipoproteins in plasma, and by modulating cellular processes involved in foam cell formation. SUMMARY: Recent studies emphasize the role played by adiponectin in the homeostasis of adipose tissue and in the pathogenesis of the metabolic syndrome, type 2 diabetes, and atherosclerosis. These pleiotropic effects make it an attractive therapeutic target for obesity-related conditions.