Etiology and systemic immunity disturbances in patients with tuboperitoneal infertility

The etiological structure of the inflammatory diseases of genitals at different levels of the reproductive tract of women with tuboperitoneal sterility was studied. The study revealed the prevalence of cocci in the cervical canal, anaerobes in the endometrium and chlamydiae in the abdominal cavity (peritoneal fluid, the ovarian capsule, fimbriated ends), as well as the presence of mixed infection in 27% of the patients under study. The specific features of immunity in women with tuboperitoneal sterility were established, which determined the main trends of the subsequent pathogenetically oriented immunocorrection.     

Electron transfer in ferredoxin: are tunneling pathways evolutionarily conserved?

A theoretical study of electron transfer (ET) pathways in a recently crystallized Clostridium acidurici ferredoxin is reported. The electronic structure of the protein complex is treated at the semiempirical extended Hückel level, and the tunneling pathways are calculated with the rigorous quantum mechanical method of tunneling currents. The model predicts two pathways between the two [4Fe-4S] cubanes: a strong one running directly from Cys(14) to Cys(43) and a weaker one from Cys(14) via Ile(23) to Cys(18), whereas other amino acids do not play a significant role in the electron tunneling. The cysteine ligands conduct almost all of the current when Ile(23) is mutated to valine in silico, so that there is no appreciable change in the ET rate. The calculated value of the transfer matrix element is consistent with the experimentally determined rate of transfer. Results of the sequence analysis performed on this ferredoxin reveal that Ile(23) is a highly variable amino acid compared with the cubane-ligating cysteine amino acids, even though Ile(23) lies directly between the donor and acceptor complexes. We further argue that the homologous proteins with a [3Fe-4S] cofactor, which does not have one of the four cysteine ligands, use the same tunneling pathways as those in this ferredoxin, on the basis of the high homology as well as the absolute conservation of Cys(14) and Cys(43) which serve as the main tunneling conduit. Our results explain why mutation of amino acids around and between the donor and acceptor cubane clusters, including that of Ile(23), does not appreciably affect the rate of transfer and add support to the proposal that there exist evolutionarily conserved electron tunneling pathways in biological ET reactions.     

The role of different microorganisms in the genesis of tubal-peritoneal infertility and in immunity

The character of microflora, directly causing inflammatory process in tuboperitoneal infertility, was studied. The study revealed the prevalence of microbial associations, Chlamydia infection was detected in half of the women, and in 17% of the patients this infection was for the first time detected in the upper section of their reproductive apparatus, which was indicative of the role of Chlamydia infection in the occlusion of the uterine tubes. Opportunistic microflora persisting in persons with defective antimicrobial protection was found. The study of local protective factors in peritoneal fluid revealed the absence of T-cell activity, which was manifested by a low level of sIL-2R and the absence of a significant rise in the level of IL-2 in peritoneal fluid in comparison with that in healthy women. In addition, a decrease in the total complement activity and in the activity of component C3 of the complement was established.     

The role of sodium-proton exchange in the regulation of the electric and contractile activity of smooth muscles

The Na+/H+-exchange inhibitor aethylisopropylamyloride was found to enhance the membrane resistance, the AP duration, and the duration of the guinea pig ureter's smooth muscle contraction. Tetraethylammonium and incubation in the Ca-free EG-TA-containing solution eliminated the activating effect of this inhibitor. Gramycidin A shortens the AP plateau. The Na+/H+-exchange mechanism seems to act under normal conditions. Alterations occurring in electrical and contractile activities of smooth muscle under the effect of the Na+/H+-exchange seem to result from the changes in the membrane Ca-dependent potassium conductivity.     

The Palaearctic centers of taxonomic diversity of fleas (Siphonaptera)

The Palaearctic flea fauna includes 921 species and 479 subspecies from 96 genera of 10 families. Of them, 858 species (94%) from 43 genera are endemic to the Palaearctic; they comprise 40% of the Palaearctic Hystrichopsyllidae, 24% of Ceratophyllidae, and 20% of Leptopsyllidae. Ranges of 581 species (63% of the Palaearctic fauna) are situated within one province or subregion of the Palaearctic. Species with ranges including a part of Asia (592) comprise 87% of the total fauna; 72% of the species (517) are endemic to the Palaearctic. The largest centers of taxonomic diversity of Palaearctic fleas are situated in the East Asian, Central Asian, and Turano-Iranian Subregions: 320 species of fleas (214 of them endemic) from 59 genera (8 endemic) are known from the East Asian Subregion; 270 species (over 120 endemic) from 54 genera (5 endemic) are distributed in the Central Asian Subregion. The Turano-Iranian fauna comprises 213 species (103 endemic) from 47 genera (3 endemic); about 160 species occur in the Turanian Subprovince closest to the Russian borders, one-third of them (52 species, or 33%) are endemic; 69 species more are endemic to the entire Asian part of the Palaearctic. Extra-Asian and extra-Siberian ranges are known in 190 flea species. In the western Palaearctic, 76 species are endemic to the European Province, and 57 species, to the Mediterranean Province; 36 species have Euro-Mediterranean distribution. The fauna of the Saharo-Arabian Subregion comprises 30 species (12 endemic), 6 species have ranges of the Mediterranean-Saharo-Arabian type. Scenarios of the origin of the Siphonaptera at the Triassic-Jurassic boundary are hypothesized. Formation of the Palaearctic flea fauna was mostly supported by the Asian-Indo-Malayan and East Asian-Western American palaeofaunal centers of taxonomic diversity. The long history of faunal exchange between the east Palaearctic and the west Nearctic is manifested by the distribution of the parasites of rodents and insectivores, fleas of the genera Stenoponia, Rhadinopsylla, Nearctopsylla, and Catallagia, belonging to several subfamilies of the Hystrichopsyllidae, as well as members of a number of other flea families. A great number of endemic species in the genera Palaeopsylla and Ctenophthalmus (Hystrichopsyllidae), both in the European and Asian parts of the Palaearctic, can be explained by the junction of the European and Asian continental platforms in the late Cretaceous and their subsequent isolation during the Paleocene. A considerable contribution to the flea fauna in the Russian territory was made by the East Asian-Nearctic center of taxonomic diversity, with a smaller role of the European palaeofauna. Immigration of species of the family Pulicidae from the Afrotropical Region is restricted to the southern territories of Russia.     

Tobacco smoking inhibits expression of proinflammatory cytokines and activation of IL-1R-associated kinase, p38, and NF-kappaB in alveolar macrophages stimulated with TLR2 and TLR4 agonists

Tobacco smoking has been associated with impaired pulmonary functions and increased incidence of infections; however, mechanisms that underlie these phenomena are poorly understood. In this study, we examined whether smokers' alveolar macrophages (AM) exhibit impaired sensing of bacterial components via TLR2 and TLR4 and determined the effect of smoking on expression levels of TLR2, TLR4 and coreceptors, and activation of signaling intermediates. Smokers' AMs exhibited reduced gene expression and secretion of proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6) and chemokines (RANTES and IL-8) upon stimulation with TLR2 and TLR4 agonists, S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-(R)-Cys-(S)-Ser-Lys4-OH trihydrochloride (Pam(3)Cys), and LPS, whereas expression of anti-inflammatory cytokines (IL-10 and IL-1 receptor antagonist) was not affected. TLR3 activation with polyinosinic-polycytidylic acid led to comparable or even higher cytokine responses in smokers' AMs, indicating that smoking-induced suppression does not affect all TLRs. Comparable expression of cytokines and chemokines was detected in PBMC and purified monocytes obtained from smokers and nonsmokers, demonstrating that the suppressive effect of smoking is restricted to the lung. TLR2/4-inducible IL-1R-associated kinase-1 (IRAK-1) and p38 phosphorylation and NF-kappaB activation was suppressed in smokers' AMs, whereas TLR2, TLR4, CD14, MD-2 mRNA levels, and TLR4 protein expression were not altered. These data suggest that changes in expression and/or activities of signaling intermediates at the postreceptor level account for smoking-induced immunosuppression. Thus, exposure of AMs to tobacco smoke induces a hyporesponsive state similar to endotoxin tolerance as manifested by inhibited TLR2/4-induced expression of proinflammatory cytokines, chemokines, and impaired activation of IRAK-1, p38, and NF-kappaB, resulting in suppressed expression of proinflammatory mediators.