Flavonoids and resveratrol as regulators of Ah-receptor activity: protection from dioxin toxicity.

In 2002 FAO and WHO published a joint appeal to state and public organizations and scientific community to take every effort to control the contents of dioxin and related biphenyls in the environment and food products. The toxic effects of dioxin are realized via its interaction with the Ah-receptor. Here we reviewed modern notions about the structure and functions of Ah-receptor. Particular attention was given to antagonists and agonists of the Ah-receptor, including various flavonoids and resveratrol.

[Immunologic monitoring of patients with cystic fibrosis: value of different laboratory findings]. / Immunologicheskii monitoring bol'nykh mukovistsidozom, znachenie razlichnykh laboratornykh pokazatelei.

Cystic fibrosis (CF) is a common, serious, and frequently fatal autosomal recessive genetic disorder associated with the poor function of chloride channels. Chronic endobronchial inflammation and bacterial infection are main causes of morbidity and mortality due to CF. The study dealt with a relationship between progression and inflammation markers. Twenty one CF children with acute pulmonary exacerbation were examined. The signs of peripheral blood inflammation (responses of lymphocytes to PHA and their sensitivity to the antiproliferative effect of glucocorticoids) and in situ inflammation markers (sputum elastase activity, IL-8 and TNF-alpha, and protein concentrations in the same sputum specimens). These laboratory findings were used to calculate a "laboratory index" (LI). The clinical status of each patient was evaluated with a "clinical index" (CI), a parameter that includes respiratory secretion cultures, pulmonary function test results, nutritional status, and the presence of disease-related complications. There was a positive linear correlation between LI and CI. The presence of P. aeruginosa was strongly associated with the changes of inflammatory markers. CF patients with prolonged P. aeruginosa infection demonstrated extremely enhanced elastase activity and elevated amounts of sputum IL-8 and TNF-alpha as compared to uninfected subjects. The lung elastase activities, sputum protein contents, and TNF-alpha levels in individuals with short-term colonization were at or below those without P. aeruginosa infection. In patients with or without short-term colonization, the normalization of laboratory parameters was strongly related to evident clinical improvement. At the same time, antibiotic treatment failed to suppress an excessive inflammatory response in the lungs of patients with prolonged P. aeruginosa infection. The importance of individual inflammation markers is discussed in the paper.

[Mechanisms of inhibiting production of tumor necrosis factor alpha by the synthetic hexapeptide--immunophane]. / Mekhanizmy ingibitsii porduktsii faktora nekroza opukhloi alph sinteticheskim geksapeptidom--immunofanom.

The authors examined the human blood mononuclear-induced tumor necrosis factor production using the new drug--the synthetic hexapeptide Immunophan. The levels of tumor necrosis factor in the supernatant liquid were measured by the enzyme immunoassay and the cytotoxic test using L-929 fibroblastoid cells. Following 2-8 hours of short-term incubation of mononuclear cells with Immunophan, there was a reduction in spontaneous or lipopolysaccharide - or ionophore A23187-induced production of tumor necrosis factor. As high as 5-20% of plastic-nonadherent cells treated with Immunophan in a concentration of 0.25 mu/ml were found to produce the same effect. Two-four hours after Immunophan activation, the cells produced into the supernatant liquid soluble factors with a molecular weight of 70-85 kD that suppressed the production and activity of tumor necrosis factor. Thus, the modulating effect of Immunophan against tumor necrosis factor production is associated with the induction of regulatory cells producing the soluble receptors of tumor necrosis factor. It is suggested that extrabody pharmacological induction of the cells that regulate the production of tumor necrosis factor, followed by their subsequent administration into the autologic organism might be used while developing new variants of extracorporeal treatments of the diseases which are characterized by the pathogenetically significant hyperproduction of the inflammatory cytokins,--tumor necrosis factor, interleukin-1, interleukin-6.

[Ecological immunodeficiency: immunogenetic aspects of its etiology and correction]. / Ekologicheskii immunodefitsit: immunogeneticheskie aspekty ego razvitiia i korektsii.

The examinations of auto-transport Kazakh drivers have indicated that there is a significant reduction in some immunological parameters HLA-B5 and HLA-DR5-proliferative responses of lymphocytes to mitogens, production of interleukin-1 and interleukin-2, activity of NK and LAK-cells. It is suggested that these impairments occur with their long-term exposure to automobile transport effluents (ATE), since the same changes in immunological parameters were found previously in the experiments with animals exposed to ATE for a long time. Some of the detected immunoresponsive disorders are associated with the availability of definite HLA antigens, such as HLA-B5 and HLA-P5. The new immunomodulating agents thymohexin (TH) and phyto-extraction drugs C4 and C6 used in vitro substantially restored the lower functional activity of immunocompetent cells and production of cytokines (thymohexin was particularly effective). The most marked recovery was observed in the drivers with the phenotype HLA-B6+ and HLA-P5+, i.e. in persons with maximally ATE-reduced immunological parameters.

[Genetic aspects of the action of immunosuppressive agents]. / Geneticheskie aspekty deistviia razlichnykh immunodepressantov.

The data were obtained formerly that mice of certain strains essentially differ in the sensitivity to the immunodepressive and antiproliferative action of the alkylating agents (so-called opposite strains: DBA/2--highly sensitive, BALB/c--resistant). It is shown in the present work that with the use of the other non-alkylating immunodepressive agents (cytarabine, cyclosporin A, dexamethasone) that differ in the action mode, DBA/2 mice retain a high sensitivity whereas BALB/c mice a low sensitivity to all the immunodepressants. The sensitivity to the immunodepressive action in vivo directly correlates with that of the immunocompetent cells in vitro. Potential mechanisms determining the same type sensitivity to diverse immunodepressant in mice belonging to the above-indicated genotypes are under discussion.

[Identification of myosin light chain 1 from human heart ventricles on two-dimensional electrophoretograms using monoclonal antibodies]. / Identifikatsiia legkoi tsepi 1 miozina iz zheludochkov serdtsa cheloveka na dvumernykh élektroforegrammakh s pomoshch'iu monoklonal'nykh antitel.

Two-dimensional electrophoresis performed according to O'Farrell was used to isolate the myosin light chain I from human heart ventricles. This chain was further used to obtain hybridomas able to secrete monoclonal antibodies. This method permits to increase the yield of monoclonal antibody-secreting hydridomas and to spare effort with regard to cultivation and testing of experimental samples.

[Analysis of the distribution of class I HLA-antigens in patients with systemic scleroderma with regard to features of the clinical course of the disease and therapy with D-penicillamine]. / Analiz raspredelenie HLA-antigenov I klassa u bol'nykh sistemnoi sklerodermiei s uchetom osobennostei klinicheskogo techeniia zabolevaniia i terapii D-penicillaminom.

The distribution of HLA-A, B, C antigens has been studied in 40 patients with systemic scleroderma and in 200 healthy individuals (all Russians). An increased frequency of the antigens B35 and Cw4 has been discovered in patients, as compared with control. When analysing different clinical and common parameters, lung affection in the systemic scleroderma patients was found to be associated with the antigen A10 (58.9% versus 21% in control, RR = 5.22, EF = 0.476, Pc = 0.0363), the presence of antinuclear antibodies being associated with the antigen B35 (50% versus 17% in control, RR = 4.8, EF = 0.396, Pc = 0.0354). The association with the antigen B8 most commonly mentioned in the literature was characteristic of the patients with an earlier onset of the disease (under 30 years) and those with the rheumatoid factor. The patients having D-penicillamine-induced complications were found to have an increased frequency of the antigen B8, as compared with the alternative group of patients (2P = 0.0430).

[Analysis of distribution of histocompatibility antigens class I and II in children with rheumatoid arthritis]. / Analiz raspredeleniia antigenov I i II klassov sistemy HLA u detei s revmatoidnym artritom.

The authors studied distribution of antigens HLA A, B, C in 115 children and of antigens HLA DR in 102 children of the Russian nationality with classic or diagnosed juvenile rheumatoid arthritis (JRA). A rise in the frequency of antigens B21, B27 and DR3 was noted as compared to the control values. Then distribution of HLA-antigens was analysed in separate groups of patients depending on the nature of the clinical course of JRA. It was characteristic of patients of patients depending on the nature of the clinical course of JRA. It was characteristic of patients with mono-oligoarthritis with an polyarticular form of JRA to exhibit a rise in the frequency of antigens B27 and DRW8, with uveitis--of antigens A2, B27 and DRW8, with a high degree of activity of the inflammatory process--B21, with an allergic variant--B21, with an articulovisceral form--B21, DR3 and DR4, with Still's disease--DR3, rheumatoid nodes--DR2 and DR3. Thus, specificity of associations was determined in most of the cases by the nature of JRA clinical course. The authors confirm the number of associations previously described in the literature abroad.

[Variability of sensitivity of lymphocytes from healthy donors to antiproliferative effect of dexamethasone and HLA antigens]. / Variabel'nost' chuvstvitel'nosti limfotsitov zdorovykh donorov k antiproliferativnomu deistviiu deksametazona i antigeny sistemy HLA.

A positive correlation between the level of lymphocyte PHA-stimulation and the degree of stimulation inhibition by dexamethasone has been established. Using regression analysis methods, healthy volunteers were divided into three groups: sensitive, intermediate and resistant. The frequency of HLA-B7, B12 and DR2 antigens was increased in the latter group.

[Use of monoclonal antibodies in comparative studies of Ca, Mg-dependent endonuclease in cell nuclei]. / Primenenie monoklonal'nykh antitel v sravnitel'nykh issledovaniiakh Ca, Mg-zavisimoi éndonukleazy kletochnykh iader.

Eight hybridoma cell lines derived from fusion between myeloma X-63 and mouse splenocytes were found to secrete monoclonal antibodies against Ca/Mg-dependent endonuclease of human spleen cell nuclei. Two of them, termed N and S, were used in comparative research of enzymes from different organs and species of animals. The data obtained show that N and S antibodies recognize different antigenic determinants of the enzyme molecule. Cross-reactions of antibodies with different antigens having similar antigenic determinants, exist in Ca/Mg-endonuclease of such species as man, mouse, rat and cattle. The evolutionary conservatism of this enzyme is suggested. The data show that the existence of tissue-specific (thymus-specific and spleen-specific) isoforms of Ca/Mg-endonuclease of cell nuclei is possible.

[Sensitivity of the splenic cells of different mouse strains to the antiproliferative action of alkylating compounds]. / Chuvstvitel'nost' kletok selezenki myshei raznykh linii k antiproliferativnomu deistviiu alkiliruiushchikh soedinenii.

A method of quantitative evaluation of lymphocytes' sensitivity to the antiproliferative effect of the alkylating drugs has been developed. Chlorbutin, mafosfamide (Asta Z 7654) and "active" metabolites of cyclophosphamide were studied. This research allowed to distinguish more sensitive strains (DBA/2 and C57BL/6) and those with low sensitivity (BALB/c and CC57BR). These differences do not depend on proliferation reaction, neither on the type of alkylating drugs nor haplotypes H-2.

[The HLA system and Coxsackie B viral myocarditis in adults]. / Sistema HLA i virusnyi Koksaki B miokardit u vzroslykh.

The distribution of HLA antigens A, B and C was studied in 152 normal donors, 53 patients with Coxsackie B virus myocarditis, 35 patients with myocarditis of unknown origin, 16 coronary patients and 14 rheumatic patients with high titres of anti-Coxsackie virus antibodies. Coxsackie virus myocarditis was associated with increased occurrence of HLA antigens A3, B40, Cw2 and A28, the increase being significant (with an adjustment to the number of the tested antigens) for A3 in severe and medium myocarditis, and B40 in patients who had developed myocarditis before age 30. Antigen Cw2 was more common in myocarditis patients with high titres of anti-Coxsackie virus B4 antibodies. The distribution of HLA antigens in coronary patients was similar to that of the controls. Rheumatic patients showed increased incidence of antigen Cw2. It is suggested that carriers of histocompatibility antigen A3 may be predisposed genetically to severe or medium Coxsackie B virus myocarditis.

[Sensitivity of the splenic immunocompetent cells of mice with different genotypes to the action of alkylating agents]. / Chuvstvitel'nost' immunokompetentnykh kletok selezenki myshei raznykh genotipov k deistviiu alkiliruiushchikh agentov.

It has been established in experiments in vitro that splenocytes of DBA/2GSto mice are more sensitive to the immunosuppressant action of the alkylating agents (cyclophosphamide, sarcolysine and thiophosphamide) than splenocytes of BALB/cGLacSto mice. Splenocytes of C3H/SnRap mice exhibit and intermediate type of sensitivity. T-lymphocytes of the spleen of BALB/cGLacSto and DBA/2GSto mice are more sensitive in vitro to the action of active metabolites of cyclophosphamide as compared to B-lymphocytes, with both types of the cells of DBA/2GSto mice being affected to a greater extent than the cells of BALB/cGLacSto mice.

[Mechanism of the suppression of the formation of immunologic memory]. / O mekhanizme supressii formirovaniia immunologicheskoi pamiati.

An extract from splenocytes of mice immunized with sheep red blood cells contains suppressor factor (SF) that specifically inhibits the primary immune response. The system of adoptive transfer was studied for the action of the SF on the formation of immunologic memory for sheep and rat blood cells. It was established that the SF carrying a receptor for specific antigen causes nonspecific suppression of the generation of immunologic memory cells. Within the system in question radioresistant T helper cells act as suppression targets. It is suggested that the final effect of the SF lies in the inhibition of the release of transmitters promoting differentiation or proliferation of T memory cells.

[Sensitivity of BALB/c and WR strain mice to the immunodepressive action of cyclophosphamide and thiophosphamide]. / Chuvstvitel'nost' myshei linii BALB/c i WR k immunodepressivnomu deistviiu tsiklofosfamida i tiofosfamida.

Experiments were made on BALB/cJ YSto and WR/Y mice to study the immunosuppressant action of cyclophosphamide (CP) and thiophosphamide (thiotepa) in vivo. WR mice were found to be significantly more sensitive to the immunosuppressant action of thiotepa than BALB/c mice and to have similar sensitivity to the action of CP. BALB/c mice appeared highly resistant to the action of both the drugs. Based on the data obtained and those reported in the literature a possible parallelism is suggested between the mutagenic and immunosuppressant action of CP and thiotepa.