Molecular Energotropic and Cellular Mechanism of the Radioprotective Action of Sulfur-Containing Biphenolic Dibasic Acids under Conditions of Lethal γ-Irradiation.

Dibasic acids (DBA) with benzene rings having substituents and connected by a sulfurcontaining bridge exhibited radioprotective effectiveness when administered in non-toxic concentrations to laboratory mice 1 h before γ-irradiation in a lethal dose of 8 Gy. The correlation of protonophore activity on bilayer lipid membranes with radioprotective (in mice) and uncoupling activity (in mitochondria) indicates a molecular protonophore uncoupling radioprotective mechanism of DBA action on mitochondria, which manifests in temporary partial inhibition of energy production. The effectiveness of DBA depends on the position and the degree of dissociation of OH-groups and increased in the presence of a sulfur-containing bridge and substituents in the series Br->Cl->NO2->COOCH3->COOH-. The higher radioprotective effect was observed for more effective uncouplers of the processes of oxidative phosphorylation and respiration of mitochondria, DBA1 preparations with OH-groups in the 2nd position of the benzene rings (80-100%), than for DBA2 with OH- in the 4th position (40-60%). The radioprotective effect of DBA was related to their antioxidant activity during and after irradiation to a lesser extent than with their uncoupling efficiency. At the cellular level, the radioprotective mechanism of DBA is related to temporary hypoxia and inhibition of metabolism leading to inhibition of generation of ROS, radicals, and LPO products.

Understanding the population structure of North American patients with cystic fibrosis.

It is generally presumed that the cystic fibrosis (CF) population is relatively homogeneous, and predominantly of European origin. The complex ethnic make-up observed in the CF patients collected by the North American CF Modifier Gene Consortium has brought this assumption into question, and suggested the potential for population substructure in the three CF study samples collected from North America. It is well appreciated that population substructure can result in spurious genetic associations. To understand the ethnic composition of the North American CF population, and to assess the need for population structure adjustment in genetic association studies with North American CF patients, genome-wide single-nucleotide polymorphisms on 3076 unrelated North American CF patients were used to perform population structure analyses. We compared self-reported ethnicity to genotype-inferred ancestry, and also examined whether geographic distribution and cystic fibrosis transmembrane regulator (CFTR) mutation type could explain the population structure observed. Although largely Caucasian, our analyses identified a considerable number of CF patients with admixed African-Caucasian, Mexican-Caucasian and Indian-Caucasian ancestries. Population substructure was present and comparable across the three studies of the consortium. Neither geographic distribution nor CFTR mutation type explained the population structure. Given the ethnic diversity of the North American CF population, it is essential to carefully detect, estimate and adjust for population substructure to guard against potential spurious findings in CF genetic association studies. Other Mendelian diseases that are presumed to predominantly affect single ethnic groups may also benefit from careful analysis of population structure.

Reticulin-M, an antianaphylactic peptide secreted by reticulo-endothelial system.

I. Moldovan (1923) demonstrated in the blood ultrafiltrate from anaphylactically prepared guinea pigs, which believed to anaphylactic shock, or which were previously injected with coloidal substances as India ink to stimulate the RES, an antianaphylactic principle named Reticulin-M(R). Authors extracted R from organs rich in RES with acetone, established their, peptidic nature and tested it on anaphylactic prepared guinea pig uterine horns in vitro. The peptides were fractioned by high voltage paper electrophoresis. The fractions were cut up in four groups, eluted and tested. The second basic group was identified as active and concentrated by acetone, recipitation. In conclusion several techniques were used to obtain, to test, to isolate and to concentrate R, a natural antianaphylactic peptidic factor, which may be a cytokine.