Synthesis of N-arylsulfonyl DL-phenylserine derivatives exhibiting anti-inflammatory activity in experimental studies

Synthesis and evaluation of anti-inflammatory activity in rats with adjuvant arthritis of aryl sulfonyl derivatives of nonproteinogenic aromatic amino acids is reported. The studied compounds were synthesized by introducing residues of benzene-, p-toluene-, and p-bromobenzene sulfonic acids into threo-DL-phenylserine and erythro-DL-p-nitrophenylserine structures. From the set of 12 compounds tested in animal screening, N-(p-bromobenzenesulfonyl)-erythro-DL-p-nitrophenylserine ethyl ester 12 demonstrated the most pronounced anti-inflammatory activity. This compound inhibited inflammation process in polyarthritis phase by 53% (P < 0.001) though it was slightly toxic (LD50 > 6,000 mg kg(-1) for mice).     

Implementation of non-invasive brain physiological monitoring concepts

The paper presents innovative methods and technology for non-invasive intracranial hemodynamics monitoring based on the measurement of brain parenchyma acoustic properties. The clinical investigation of new technology shows the similarity between the invasively recorded intracranial pressure (ICP) and non-invasively recorded intracranial blood volume (IBV) pulse waves, slow waves and slow trends under intensive care unit (ICU) conditions. Also, the applicability of the non-invasive IBV slow wave monitoring technique for cerebrovascular autoregulation non-invasive long-term monitoring is demonstrated by theoretical and experimental studies.     

Nicotine 5'-oxidation and methyl oxidation by P450 2A enzymes.

In smokers, the primary pathway of nicotine metabolism is P450 2A6-catalyzed 5'-oxidation. The nicotine Delta(5'(1'))-iminium ion product of this reaction is further metabolized to cotinine by aldehyde oxidase. Previous investigators have reported kinetic parameters for cotinine formation using human liver cytosol as a source of aldehyde oxidase. Using [5-(3)H]nicotine and radioflow high-performance liquid chromatography analysis, we determined kinetic parameters for nicotine 5'-oxidation by P450 2A6 and the closely related human extrahepatic P450 2A13 as well as the rodent P450s 2A3, 2A4, and 2A5. The formation of both cotinine and nicotine Delta(5'(1'))-iminium ion was monitored. The K(m) and V(max) values for P450 2A6 were 144 +/- 15 muM and 1.30 +/- 0.05 pmol/min/pmol, respectively. Previously reported K(m) values for cotinine formation by P450 2A6 in the presence of cytosol were much lower, ranging from 11 to 45 muM. P450 2A13 was a somewhat better catalyst of nicotine Delta(5'(1'))-iminium formation, with 2-fold lower K(m) and 2-fold higher V(max) values than P450 2A6. The rat P450 2A3 and the mouse P450 2A5, which are 85 and 84% identical to P450 2A6, were much more efficient catalysts of nicotine 5'-oxidation. P450 2A4 was not an efficient catalyst of nicotine metabolism. Whereas 5'-oxidation was the major pathway of nicotine metabolism for all five P450 2A enzymes, these enzymes also catalyzed methyl oxidation. Nornicotine, the product of this reaction was detected as 5 to 15% of the total nicotine metabolites. Nornicotine is the amine precursor to the esophageal carcinogen N'-nitrosonornicotine. Therefore, methyl oxidation of nicotine by P450 2A6 or P450 2A13 followed by nitrosation of nornicotine are possible endogenous pathways of N'-nitrosonornicotine formation.     

Protein Tyrosine Phosphatase SHP2 Controls Interleukin-8 Expression in Breast Cancer Cells

Journal of Mammary Gland Biology and Neoplasia - Treatment of metastasis remains a clinical challenge and the majority of breast cancer-related deaths are the result of drug-resistant metastases....     

Embryotoxicity of Quantum Dots in Rainbow Trout <Emphasis Type="Italic">Oncorhynchus mykiss</Emphasis> During the Hatching Period

Due to the active development and application of nanotechnology, nanoparticles have emerged as a new class of environmental pollutants. The aim of the study was to investigate quantum dots (QDs) access routes and distribution in embryos and larvae of rainbow trout Oncorhynchus mykiss and to determine the toxicity of QDs to rainbow trout larvae depending on the duration of exposure. CdSe/ZnS–COOH QDs at sublethal concentration was used during the toxicity test (1, 4 and 14 days). The results showed that QDs could get from the solutions into the larvae after hatching. QDs induced a significant increase in mortality, gill ventilation frequency and behavioral responses and a decrease in relative body mass in larvae at the end of the test. Larvae exposed to QDs were found to possess developmental malformations (blood clots). It was found that biological responses of larvae significantly depended on the duration of exposure to QDs.     

Effects of age, period and cohort on stroke mortality among a middle-aged Lithuanian urban population from 1980 to 2004

AIMS: The main purpose of this paper was to assess the effect of age, period, and cohort on stroke mortality rates among a Lithuanian urban population aged 25-64 years (1041 men and 724 women) between 1980 and 2004. METHODS: Routine stroke mortality data were obtained from official Kaunas region mortality register by codes 430-438 and I60-I69 in the 9th and in the 10th revisions of the International Classifications of Diseases (ICD), respectively. Mortality rates per 100,000 persons for men and women were age-adjusted using the age distribution of the European Standard Population. Age-specific mortality rates were analysed by sex, period, and birth cohort in eight 5-year age groups and five 5-year age groups. Goodness of fit of the Poisson regression models were evaluated using Pearson and Freeman-Tukey residuals. The age-period and age-period-cohort models provided a significantly better fit than a model with the factors ;;age' and ;;cohort'. RESULTS: During the study period, mortality rates decreased from 46.8 to 33.0 per 100,000 for men, and from 20.2 to 18.1 per 100,000 for women (average annual decrease of -1.3%, p<0.1 for men, and -1.6%, p<0.03 for women). An age effect was present in both sexes. The definite upward period effect was observed from 1990 to 1994 both among men and women, and was followed by a sharp fall during 2000-4. Cohort and period effects have contained relevant information which partially explained trends in stroke mortality among a 25-64 year-old Lithuanian urban population. CONCLUSIONS: During the period of 1980-2004, the mortality trend declined among women only. The period effect contains relevant information for the explanation of increasing mortality rates during 2000-4 among men and women. The Poisson regression models could be applied for the examination and explanation of the different causes of the population mortality.