Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines and chemotherapeutic agents

Molecular Biology - Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic...     

The effect of Mycoplasma arthritidis superantigen on immunogenesis in transplacental infection

The immune responsiveness of the progeny of BALB/c mice, responsive to M. arthritidis superantigen (MAS), and C57BL/6 mice, nonresponsive to MAS, infected with M. arthritidis during the second half of pregnancy was studied. The investigation revealed that in responsive animals the proliferative response of spleen cells to MAS was suppressed with the level of response to concanavalin A remaining unchanged. The spleen cells of the test mice reacted to syngenic intact cells as to xenogenic ones and suppressed reaction to MAS and the production of interleukin 1 in the culture of spleen cells taken from the intact syngenic animals. The data obtained in this study suggest that after the infection of pregnant BALB/c mice with M. arthritidis immune tolerance to MAS developed in their progeny, which was accompanied by the induction of suppressor cells inhibiting the production of interleukin 1.     

Dependence of anxiolytic effects of the dipeptide TSPO ligand GD-23 on neurosteroid biosynthesis

The elevated plus maze test showed that GD-23 (N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide), an original dipeptide ligand of TSPO, exerted anxiolytic effect when injected intraperitoneally at a dose of 0.5 mg/kg. This effect was completely blocked by the selective neurosteroid synthesis inhibitors, enzymes trilostane and finasteride. The same inhibitors do not prevent the anxiolytic effects of the benzodiazepine tranquillizer diazepam. The results of the study indicate the selective neurosteroidogenic mechanism of the anxiolytic action of GD-23.     

Epizootics of "avian" influenza as the manifestation of pandemic

In this review of literature modern notions on the role of birds in the evolution of the pathogenicity signs and immune system of the main and intermediate hosts of influenza viruses, as well as on the mechanisms of overcoming interspecific barriers, are analyzed. The chronology of the spread of "avian" influenza among humans, starting from 1997, the properties of the natural reservoir of this infection, and in particular influenza viruses A, the ways of their variability and evolution are presented. The conclusion has been made that the mixing, joint evolution, recombination and reassortment of viral genomes may be caused by global events in individual geographical regions.     

Effect of additional disease (Comorbidity) on association of allergic rhinitis with KCNE4 gene rs12621643 variant

Analysis of association of allergic rhinitis with the KCNE4 gene rs12621643 variant was conducted in Russian residents of West Siberia (taking into account comorbidity with bronchial asthma). It was found that, among individuals without bronchial asthma, the frequencies of the KCNE4*G allele and KCNE4*G/G genotype are significantly higher in patients with rhinitis compared to individuals without it. At the same time, no association of rs12621643 with rhinitis was detected in the group of individuals with bronchial asthma. The data obtained indicate the association of the KCNE4 gene variability with allergic rhinitis, although the effect of this gene relative to the development of the disease can be leveled against a background of the manifestation of another atopic disease.     

The use of T-activin for the prevention of congenital influenzal infection in mice and the correction of the immune deficiency

Viremia accompanying influenza infection and the possibility of transplacental passage of the virus into the fetus make it expedient to develop measures for the prophylaxis of intrauterine infection of the fetus in case of influenza during pregnancy. The work presents the optimum scheme of administration of T-activin for prophylactic purposes to pregnant mice with acute influenza infection. Besides, the use of T-activin for immunocorrection in case of established congenital influenza infection in mice is proposed.     

A study of the biologically active conformation of the cholecystokinin-4 dipeptide analogue GB-115

The biologically active conformation of N-(6-phenylhexanoyl)glycyl-tryptophan amide (GB-115), a highly active cholecystokinin-4 retro dipeptide analogue with the anxiolytic activity, has been studied using the conformational analysis by ¹H NMR spectroscopy in solution and the method of sterically restricted analogues. A study of the relationship between the preferable conformation in solution and the anxiolytic activity in the series of GB-115 derivatives showed that the biologically active conformation of this compound is the β-turn. Based on the data on the nuclear Overhauser effect ¹H NMR spectroscopy, this structure was identified as the β-turn of type II. Subsequent synthesis and study of the pharmacological activity of novel sterically restricted analogues of dipeptide GB-115: (2S)-2-{(3R)-3-[(6-phenylhexanoyl)amino]-2-oxopyrrolidine-1-yl}-3-(1H-indole-3-yl)propionic acid ethyl ester, N-(6-phenylhexanoyl)glycyl-N ^α-methyltryptophan ethyl ester, (2S)-2-[(10,11-dihydro-5H-dibenzo[b, f]azepin-5-ylcarbonyl)amino]-3-(1H-indole-3-yl)propionic acid methyl ester, and (2S)-2-[({3-[(ethoxycarbonyl)amino]-10,11-dihydro-5H-dibenzo[b, f]azepin-5-yl}carbonyl)amino]-3-(1H-indole-3-yl)propionic acid methyl ester confirmed that the β-turn of type II is the active conformation of GB-115.     

Cytoskeleton alterations of erythrocytes from patients with Fanconi's anemia

Fanconi's anemia (FA) is a very rare genetically heterogeneous disease which has been hypothesized to be defective in the detoxification of reactive oxygen species. In this work we report the results obtained by morphometric and biochemical analyses on the red blood cells (RBCs) from FA patients. With respect to RBCs from healthy donors the following changes have been detected: (i) a variety of ultrastructural alterations, mainly surface blebbing typical of acanthocytes and stomatocytes; (ii) a significant quantitative increase of these altered forms; (iii) modifications of spectrin cytoskeleton network; (iv) an altered redox balance, e.g. a decreased catalase activity and significant variations in the GSSG/GSH ratio. We hypothesize that remodeling of the redox state occurring in FA patients results in cytoskeleton-associated alterations of red blood cell integrity and function.     

Coenzyme Q10-containing composition (Immugen) protects against occupational and environmental stress in workers of the gas and oil industry

The manual workers of the gas-and-oil extraction industry are exposed to hostile environmental and occupational conditions, resulting in elevated mortality and disability, due to chronic neurological and cardiovascular diseases. We evaluated the degree of oxidative stress, often associated with these pathological features, in the blood of manual and office employees of Russian Siberian extraction plants, and their psycho-physiological conditions. Results showed increased levels of spontaneous (p < 0.05) and PMA-activated (p < 0.01) luminol-dependent chemiluminescence (LDCL) in the white blood cells (WBC), and decreased peroxynitrite levels (p < 0.05) in the group of manual workers, and less markedly in the clerks and technicians working on spot, vs. a control group of city clerks. Superoxide release by WBC, and plasma/WBC membrane ubiquinol levels did not display major differences in the three groups. A relevant percentage of manual/office workers of extraction platforms presented impaired cardiovascular and neurological functions. The short term administration of a nutraceutical formulation based on coenzyme10, vitamin E, selenium, methionine and phospholipids led to significant improvement of cardiovascular parameters and psycho-emotional status, consistent with the normalization of LDCL and peroxynitrite production by WBC, with a good compliance to treatment confirmed by the increased blood levels of ubiquinol.