Antimutagenic activity of Armoracia rusticana, Zea mays and Ficus carica plant extracts and their mixture

Antimutagenic action of plant extracts of Armoracia rusticana, Ficus carica, Zea mays and their mixture on environmental xenobiotics has been investigated. The plant extracts and their mixture decreased the level of mutations induced by N-metil-N'-nitro-N-nitrozoguanidin (MNNG) in Vicia faba cells, chlorophyll mutations in Arabidopsis thaliana and NaF induced mutability in rat marrow cells. The studied plant extracts and their mixture demonstrate the ability to decrease the genotoxicity of environmental mutagens.     

An association between a NQO1 genetic polymorphism and risk of lung cancer

NAD(P)H:quinone oxidoreductase (NQO1) is a detoxification enzyme that protects against the regeneration of reactive oxygen species chemically induced by oxidative stress, cytotoxicity, mutagenicity, and carcinogenicity. The protection conferred by NQO1 protein reduces certain environmental carcinogens, such as nitroaromatic compounds, heterocyclic amines, and possible cigarette smoke condensate. The gene coding for NQO1 has a genetic polymorphism (C-->T) at nucleotide position 609 (i.e. amino acid codon 187) of the NQO1 cDNA. This polymorphism was shown to reduce NQO1 enzyme activity, thereby diminishing the protection provided by NQO1. Therefore, we hypothesized that individuals with the variant NQO1 genotype are at higher risk for lung cancer. Using a case-control study, we genotyped the NQO1 variants successfully by PCR-RFLP in 826 lung cancer patients and 826 healthy control subjects matched for age, sex, ethnicity, and smoking status. The frequency of the NQO1 T-allele was statistically significantly different among three ethnic groups (p<0.001). In further analysis of Caucasians, the variant NQO1 genotypes (CT and TT) were associated with a marginally increased lung cancer risk (OR=1.19; 95% CI: 0.95-1.50). The elevated lung cancer risk was only evident in younger individuals (age <62 years old) (OR=1.46; 95% CI: 1.04-2.05), women (OR=1.89; 95% CI: 1.33-2.68), and never smokers (OR=1.80; 95% CI: 1.03-3.13). Furthermore, we found a statistically significant trend in the development of lung cancer at an early age in women with increasing copies of the variant allele (p=0.03). These results suggest that the NQO1 variant genotype may modulate lung cancer risk, especially in younger individuals (age<62), women, and never smokers.     

High-performance liquid chromatographic determination of vertilmicin in rat plasma using sensitive fluorometric derivatization

A sensitive and reliable high-performance liquid chromatographic method was developed for the determination of vertilmicin in rat plasma. Derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) followed by C(18) reversed-phase chromatography allowed the fluorimetric detection of vertilmicin. Optimal conditions for the derivatization of vertilmicin are described. The limit of quantification was 0.02 mg/L. The pharmacokinetics of vertilmicin was studied in 24 rats following intramuscular injection (i.m.) of different doses (4, 8, 16, 32 mg/kg of body weight). The pharmacokinetic parameter values were estimated by use of 3P97 program. In this study, we assessed the dose proportionality of vertilmicin after single intramuscular injection doses and obtained new information on the pharmacokinetics of the compound.     

A high-frequency lung injury mechanism in blunt thoracic impact

When a mechanical load is applied very rapidly to the thoracic wall, part of the internal damage is suspected to be due to a "high-frequency" injury mechanism, that is, a phenomenon in which waves are involved. This paper addresses a specific high-frequency mechanism for lung injury in which a stress wave is generated through rapid acceleration of the body wall. Displacement-related injuries, which are rather "low-frequency" phenomena, are not considered. The present work was done in the context of assessing behind armor blunt trauma (injury to thoracic organs occurring when a bullet is stopped by a body armor) through mathematical modeling. One aspect of the thorax response to high-speed blunt impact and an associated injury mechanism are investigated based on an idealized model of thorax and a set of computations presented in previous papers. The injury mechanism considered elucidates a possible mathematical relationship between the acceleration at the surface of the thoracic wall and the occurrence of lung injury.     

Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse

Allergic pathologies are often associated with IgE production, mast cell activation, and eosinophilia. PGD2 is the major eicosanoid, among several inflammatory mediators, released by mast cells. PGD2 binds to two membrane receptors, D prostanoid receptor (DP)1 and DP2, endowed with antagonistic properties. In humans, DP2 is preferentially expressed on type 2 lymphocytes, eosinophils, and basophils and mediates chemotaxis in vitro. Although not yet supported by in vivo studies, DP2 is thought to be important in the promotion of Th2-related inflammation. Herein, we demonstrate that mouse eosinophils express both DP1 and DP2 and that PGD2 exerts in vitro chemotactic effects on eosinophils through DP2 activation. Furthermore, 13,14-dihydro-15-keto-PGD2, a specific DP2 agonist not only increases eosinophil recruitment at inflammatory sites but also the pathology in two in vivo models of allergic inflammation: atopic dermatitis and allergic asthma. By contrast, DP1 activation tends to ameliorate the pathology in asthma. Taken together, these results support the hypothesis that DP2 might play a critical role in allergic diseases and underline the interest of DP2 antagonists in human therapy.     

Incorporation of the V-ATPase inhibitors concanamycin and indole pentadiene in lipid membranes. Spin-label EPR studies

The incorporation of concanamycin A, a potent inhibitor of vacuolar ATPases, into membranes of dimyristoyl phosphatidylcholine has been studied by using EPR of spin-labelled lipid chains. At an inhibitor/lipid ratio of 1:1 mol/mol, concanamycin A broadens the chain-melting transition of the phospholipid bilayer membrane, and effects the lipid chain motion in the fluid phase. The outer hyperfine splitting of a spin label at the C-5 position and the line widths of a spin label at the C-14 position of the lipid chain are increased by concanamycin A. Considerably larger membrane perturbations are caused by equimolar admixture of a designed synthetic 5-(5,6-dichloro-2-indolyl)-2,4-pentadienoyl V-ATPase inhibitor. These results indicate that concanamycin A intercalates readily between the lipid chains in biological membranes, with minimal perturbation of the bilayer structure. Essentially identical results are obtained with concanamycin A added to preformed membranes as a concentrated solution in DMSO, or mixed with lipid in organic solvent prior to membrane formation. Therefore, the common mode of addition in V-ATPase inhibition assays ensures incorporation of concanamycin into the lipid bilayer milieu, which provides an efficient channel of access to the transmembrane domains of the V-ATPase.     

The protein-lipid interface: perspectives from magnetic resonance and crystal structures

Lipid-protein interactions in membranes are dynamic, and consequently are well studied by magnetic resonance spectroscopy. More recently, lipids associated with integral membrane proteins have been resolved in crystals by X-ray diffraction, mostly at cryogenic temperatures. The conformation and chain ordering of lipids in crystals of integral proteins are reviewed here and are compared and contrasted with results from magnetic resonance and with the crystal structures of phospholipid bilayers. Various aspects of spin-label magnetic resonance studies on lipid interactions with single integral proteins are also reviewed: specificity for phosphatidylcholine, competition with local anaesthetics, oligomer formation of single transmembrane helices, and protein-linked lipid chains. Finally, the interactions between integral proteins and peripheral or lipid-linked proteins, as reflected by the lipid-protein interactions in double reconstitutions, are considered.     

弗氏2a志贺氏菌2457T株yciD基因缺失突变株的构建

目的:构建弗氏2a志贺氏菌2457T株yciD基因缺失突变体,以研究yciD基因的功能。方法:根据弗氏2a志贺氏菌2457T株基因组全序列,采用Red重组系统对yciD基因进行缺失,并经PCR和SDS-PAGE证实;对野生株和突变株的生长状态及生化反应进行比较研究。结果:构建了弗氏2a志贺氏菌2457T株的yciD基因缺失突变株2457TΔyciD,该突变株外膜蛋白样品中缺失了一条相对分子质量与从yciD基因推导的蛋白相当(约22000)的蛋白带。该突变株比野生株生长快,利用葡萄糖和甘露醇的能力也比野生株大为增强。结论:获得了弗氏2a志贺氏菌2457T株的yciD基因缺失突变株。