Simulation of individual risk based on the results of exercise tests and analysis of risk factors

The materials of a cross-sectional and prospective Russian-US population study (the Russian Lipid Research Clinics Prevalence Study) have been used to develop models intended for estimating the probability of death from coronary heart disease, all cardiovascular disease, and all causes over 10 and 20 years. The prediction was performed by constructing artificial neural networks. Testing on an independent sample has shown an accuracy of 66–73%.     

Allosteric transitions in cytochrome P450eryF explored with pressure-perturbation spectroscopy, lifetime FRET, and a novel fluorescent substrate, Fluorol-7GA

To establish a direct method for monitoring substrate binding in cytochrome P450eryF applicable at elevated hydrostatic pressures, we introduce a laser dye Fluorol-7GA (F7GA) as a novel fluorescent ligand. The high intensity of fluorescence and the reasonable resolution of the excitation band from the absorbance bands of P450 allowed us to establish highly sensitive binding assays compatible with pressure perturbation. The interactions of F7GA with P450eryF cause an ample spin shift revealing cooperative binding ( S50 = 8.2 +/- 1.3 microM; n = 2.3 +/- 0.1). Fluorescence resonance energy transfer (FRET) experiments suggest the presence of at least two substrate binding sites with apparent K D values in the ranges of 0.1-0.3 and 6-9 microM. Similar to that observed earlier with CYP3A4, increasing hydrostatic pressure does not cause either a complete dissociation of the substrate complexes or a displacement of the spin equilibrium toward the low-spin state. Rather, increased pressure enhances the cooperativity of the F7GA-induced spin shift, so that the Hill coefficient approaches 3 at 2 kbar. Lifetime FRET experiments revealed an important increase in the affinity of the enzyme for F7GA at elevated pressures, suggesting that the binding of the ligand induces a conformational transition associated with an important increase in the level of protein hydration. This transition largely attenuates the solvent accessibility of the heme pocket and causes an unusual stability of the high-spin, substrate-bound enzyme at elevated pressures.     

Replication Protein RepN Encoded by the RC Plasmid of Thermophilic Bacterium Thermoanaerobacterium saccharolyticum: Mutation Analysis and Deletion Mapping of Domains Responsible for Its Lethal Effect

Amino acid sequence analysis of the product encoded by repN of Thermoanaerobacterium saccharolyticum (Clostridium thermosaccharolyticum) pNB2, which is capable of rolling-circle (RC) replication, revealed all known motifs conserved among replication (Rep) proteins that initiate RC replication of plasmids related to pC194/pUB110. Using the T7 expression system in Escherichia coli, RepN was identified as a 35K protein. Its lethal effect on bacterial cells was unusually high for a protein of the kind. Mutation analysis of the potential active centers (Y85F and Y211F) showed that the lethal effect of RepN is not associated with its putative topoisomerase (relaxase) activity. On evidence of deletion mapping, the lethal effect was attributed to the N- and C-terminal domains, each accounting for about 30% of the total protein. The RepN fragments essential for the lethal effect were found to share a motif without appreciable homology to known conserved motifs. The high lethal effect of RepN was assumed to result from duplication of the motif and to play an adaptive role, providing for stable maintenance of the AT-rich plasmid in thermophilic bacterial cells.     

Efficacy of levofloxacin (Tavanic) in the treatment of children with chronic pulmonary diseases]

The efficacy of the fluoroquinolone levofloxacin in the treatment of 35 children with bronchopulmonary disease exacerbation was practically the same as that of amoxycillin/clavulanate, cefotaxime or ceftriaxone. The clinical and bacteriological results were favourable. The eradication of the pathogens responsible for the bronchopulmonary inflammations in 86% of the patients was stated. There is no doubt that fluoroquinolones should not be widely used in pediatrics. They should be considered as reserve drugs for the treatment of severe cases when the routine agents fail. Their use is justified when the situation is risky and the data on the pathogen susceptibility to the drugs are available. Still, levofloxacin is the most safe fluoroquinolone with low hepatotoxicity and lower effect on the central nervous system. The episodes of its negative cardiovascular action are less frequent. Moreover, the most frequent side effects of fluoroquinolones such as nausea, diarrhea or vomiting are less frequent with the use of levofloxacin. No signs of arthropathy in the patients treated with levofloxacin were observed in our trial.     

N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts

A study was designed to document and quantify the changes in lens clarity over 6 and 24 months in 2 groups of 49 volunteers (76 eyes) with an average age of 65.3 +/- 7.0 enrolled at the time of diagnosis of senile cataracts of minimal to advanced opacification.The patients received N-acetylcarnosine, 1% sol (NAC) (26 patients, 41 eyes = Group II), placebo composition (13 patients, 21 eyes) topically (two drops, twice daily) to the conjunctival sac, or were untreated (10 patients, 14 eyes); the placebo and untreated groups were combined into the control (reference) Group I. Patients were evaluated upon entry, at 2-month (Trial 1) and 6-month (Trial 2)-intervals for best corrected visual acuity (b/c VA), by ophthalmoscopy and the original techniques of glare test (for Trial 1), stereocinematographic slit-image and retro-illumination photography with subsequent scanning of the lens. The computerized interactive digital analysis of obtained images displayed the light scattering/absorbing centers of the lens into 2-D and 3-D scales.The intra-reader reproducibility of measuring techniques for cataractous changes was good, with the overall average of correlation coefficients for the image analytical data 0.830 and the glare test readings 0.998. Compared with the baseline examination, over 6 months 41.5% of the eyes treated with NAC presented a significant improvement of the gross transmissivity degree of lenses computed from the images, 90.0% of the eyes showed a gradual improvement in b/c VA to 7-100% and 88.9% of the eyes ranged a 27-100% improvement in glare sensitivity. Topographic studies demonstrated less density and corresponding areas of opacification in posterior subcapsular and cortical morphological regions of the lens consistent with VA up to 0.3. The total study period over 24 months revealed that the beneficial effect of NAC is sustainable. No cases resulted in a worsening of VA and image analytical readings of lenses in the NAC-treated group of patients. In most of the patients drug tolerance was good. Group I of patients demonstrated the variability in the densitometric readings of the lens cloudings, negative advance in glare sensitivity over 6 months and gradual deterioration of VA and gross transmissivity of lenses over 24 months compared with the baseline and 6-month follow-up examinations. Statistical analysis revealed the significant differences over 6 and 24 months in cumulative positive changes of overall characteristics of cataracts in the NAC-treated Group II from the control Group I.The N-acetylated form of natural dipeptide L-carnosine appears to be suitable and physiologically acceptable for nonsurgical treatment for senile cataracts.     

Advances and prospects of a combined therapy of acute radiation injury in experiments

We present the results of a long-standing experimental development of ways and means for acute radiation sickness treatment that have been authorized for application in medicine and are mostly aimed at large-scale accidental injuries. The paper describes means for early treatment (prodigiosan, desoxynate, typhoid vaccine, proteus vaccine), a myeolopoiesis stimulant (estradiol dipropionate), a detoxication procedure (hemosorption), substitution therapy with bone marrow cells and peripheral blood mononuclears, anti-infectious schemes comprising antibiotics and polyvitamins.     

Annual variation in hematological indices in a fluctuating population of bank vole (<Emphasis Type="Italic">Clethrionomys glareolus</Emphasis>)

The quantitative and structural hematological indices were studied in bank vole in different reproductive states (overwintered individuals, mature underyearlings, and immature underyearlings) in different years corresponding to different phases of the population cycle. The annual changes in certain hematological indices have been revealed for each reproductive state irrespective of the population cycle phase.