Telmisartan Attenuates Colon Inflammation,Oxidative Perturbations and Apoptosis in a Rat Model of Experimental Inflammatory Bowel Disease

Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. Telmisartan (TLM) is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS)-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o.) attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI), colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α), prostaglandin E₂ (PGE₂) and myeloperoxidase (MPO) activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10). TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB) p65 and mRNA of cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to colon injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO) besides boosting glutathione (GSH), total anti-oxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of colonic inflammation, oxidative stress and apoptosis.     

Seasonal fluctuations of the testicular androgenic function in rats

Testicular steroid-delta 5-3 beta-ol-dehydrogenase activity and plasma testosterone level in pubertal Wistar rats in spring and summer are 2-4 times higher than in autumn and winter. On the contrary the weight of the ventral prostate and seminal vesicles is lower in summer as compared with that in other seasons. This divergence is probably caused by fluctuations of the glandular secret content.     

Importance of 3-Hydroxy Fatty Acid Composition of Lipopeptides for Biosurfactant Activity

Biosurfactant production may be an economic approach to improving oil recovery. To obtain candidates most suitable for oil recovery, 207 strains, mostly belonging to the genus Bacillus, were tested for growth and biosurfactant production in medium with 5% NaCl under aerobic and anaerobic conditions. All strains grew aerobically with 5% NaCl, and 147 strains produced a biosurfactant. Thirty-five strains grew anaerobically with 5% NaCl, and two produced a biosurfactant. In order to relate structural differences to activity, eight lipopeptide biosurfactants with different specific activities produced by various Bacillus species were purified by a new protocol. The amino acid compositions of the eight lipopeptides were the same (Glu/Gln:Asp/Asn:Val:Leu, 1:1:1:4), but the fatty acid compositions differed. Multiple regression analysis showed that the specific biosurfactant activity depended on the ratios of both iso to normal even-numbered fatty acids and anteiso to iso odd-numbered fatty acids. A multiple regression model accurately predicted the specific biosurfactant activities of four newly purified biosurfactants (r² = 0.91). The fatty acid composition of the biosurfactant produced by Bacillus subtilis subsp. subtilis strain T89-42 was altered by the addition of branched-chain amino acids to the growth medium. The specific activities of biosurfactants produced in cultures with different amino acid additions were accurately predicted by the multiple regression model derived from the fatty acid compositions (r² = 0.95). Our work shows that many strains of Bacillus mojavensis and Bacillus subtilis produce biosurfactants and that the fatty acid composition is important for biosurfactant activity.     

Characteristic radiation of nitrogen under subnanosecond breakdown in a highly nonuniform electric field near the positive-polarity electrode

Results are presented from experimental studies of elevated-pressure diffuse discharge in a highly nonuniform electric field. It is shown that, in discharges in nitrogen and air, the characteristic radiation (the K-line of nitrogen) is generated at the positive polarity of the electrode with a small curvature radius. X-ray bremsstrahlung from the anode was detected in a discharge in atmospheric-pressure air at a 12-kV amplitude of the incident voltage pulse.     

3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: a novel series of mGluR2 positive allosteric modulators

The synthesis and structure-activity relationship (SAR) of a novel series of 3-(imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers, derived from a high throughput screening (HTS), are described. Subsequent optimization led to identification of potent, metabolically stable and orally available mGluR2 positive allosteric modulators (PAMs).     

Features of lung tissue cell membrane lipid composition under acute emotional stress in rats

The lipid composition of the lung plasmatic membrane in rats which have been under the acute emotional pain stress action is studied. These results are compared with the control group of animals. It is shown that at acute stress the changes of lipid composition of the lung plasmatic membranes are manifested in decrease the phospholipids and increase of cholesterol levels. The correlation of phospholipids/cholesterol in plasmic membranes in the lungs decreases at stress. At the same time the decrease of triglyceroles and diglyceroles contents is observed as well as the increase of fat acids' number. The changes that take place in the lipid contents of the lung plasmatic membranes at acute stress can play an essential role in the mechanism of cell damage development.     

Dynamic study of the cytogenetic effects in blood lymphocytes from humans living in the Chernobyl Atomic Energy Station exclusion zone without permission

The cytogenetic examination of a group of people, self-residing in ChNPP Exclusion Zone with soil contamination density 137Cs 74-477 kBq/m2, 90Sr 33-289 kBq/m2, 238, 239 + 240Pu 1.5-10.0 kBq/m2, was conducted in 1998-1999 and also 2001. It is shown, that after 12-15 years of the accident the level of chromosome damages in Zone self-residents' lymphocytes detected by a routine analysis is higher then at the residents of control Yagotin district, Kiev region and comes to a plateau. Lymphocytes with multiple chromosome damages are detected. The probability of its transuranium elements induction which are present in the Zone is discussed at present.     

Lysine Dendrimers and Their Starburst Polymer Derivatives: Possible Application for DNA Compaction and in vitro Delivery of Genetic Constructs

We attempted to find some compounds for the effective delivery of gene constructs into cells and obtained two trispherical dendrimers on the basis of lysine, (Lys)₈-(,-Lys)₄-(,-Lys)₂-(,-Lys)-Ala-NH₂ (D1) and ((Lys)₈-(,-Lys)₄-(,-Lys)₂-,-Lys)-Ala-[Lys(Plm)]₂-Ala-NH₂ (D2), as well as the starburst polymeric derivatives of D1, (pVIm) ₈ -D1 and (pLys) _n -D1, containing poly(N-vinylimidazole) and polylysine chains single-point bound to the dendrimer amino groups. The conditions of dendrimer–plasmid DNA complex formation were studied. The intracellular localization of these complexes and the expression of gene constructs delivered with their help were analyzed in transfection experiments on the HeLa cell cultures of human epithelial carcinoma and on mouse C2C12 myoblasts. It was found that the chemical structure of dendrimer D1 and its derivatives significantly affected the structure and properties of complex.     

Early postnatal effects of prenatal exposure to glucocorticoids on testosterone metabolism and biogenic monoamines in discrete neuroendocrine regions of the rat brain

We investigated the effects of hydrocortisone acetate and dexamethasone administered to pregnant rats during the last gestational week on sexual differentiation of testosterone metabolism and biogenic monoamine contents and turnover in the discrete brain regions in 10-day-old offspring. In the preoptic area, sex-dependent differences in aromatase activity were attenuated by prenatal glucocorticoids. Prenatal dexamethasone but not hydrocortisone acetate caused the inversion of sexual dimorphism of 5alpha-reductase activity in the preoptic area. In the brain preoptic area of the male pups prenatally exposed to hydrocortisone acetate, a decrease in noradrenaline turnover was found. Dopamine turnover in the preoptic area and 5-hydroxytryptamine metabolism in the preoptic area and medial basal hypothalamus increased in females as a result of hydrocortisone acetate treatment. Our results indicate that excess glucocorticoids in prenatal life modifies the basic neurochemical and neurophysiological mechanisms of sexual brain differentiation and might contribute to behavioral and reproductive disorders in adulthood.