Does Manganese Protect Cultured Human Skin Fibroblasts Against Oxidative Injury by Uva, Dithranol and Hydrogen Peroxide?

Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidative injury on cultured human skin fibroblasts. Dithranol, hydrogen peroxide and UV-A radiation (375 nm) were employed as oxidative stressors. The supply of manganese chloride produced an increase in cellular content of this element up to 24 fold without concomitant elevation of MnSOD activity. Nevertheless, manganese protects cells against two of the three ROS generating systems assessed, namely hydrogen peroxyde and UV-A. This protective effect depends on the concentration of manganese in the medium, 0.1 mM and 0.2 mM protect against UVA cytotoxicity, only 0.2 mM protects against H₂O₂ cytotoxicity.     

Risk factors for early death in non-insulin dependent diabetes and men with known glucose tolerance status.

OBJECTIVE--To identify risk factors for all cause mortality according to glucose tolerance status. DESIGN--Cohort study with an average 15.6 years'' follow up. SETTING--Paris, France. SUBJECTS--7166 working men aged 44-55 in 1968-72 in the Paris prospective study cohort, with non-insulin dependent diabetes or known result of two hour 75 g oral glucose tolerance test. MAIN OUTCOME MEASURES--Risk factors for death from all causes. RESULTS--128 men were known to be diabetic, 180 had diabetes diagnosed, and 697 had impaired glucose tolerance diagnosed. Compared with normoglycaemic men the relative risks of death in these groups were 2.0 (95% confidence interval 1.4 to 3.0), 2.7 (2.0 to 3.6), and 1.6 (1.3 to 2.0) respectively. Obesity, smoking, high blood pressure, and high non-esterified fatty acid concentration were risk factors for death in all subjects and were unaffected by glucose tolerance. The risks for fasting and two hour insulin concentrations and mean corpuscular volume were two times higher in known diabetic men than in men not known to be diabetic. Central obesity was significant only in men not known to be diabetic (1.6 (1.4 to 1.9)). In known diabetic men a two hour glucose concentration higher than 11.1 mmol/l carried a relative risk of death of 3.8 (1.4 to 9.4). CONCLUSIONS--Diabetic men have similar risk factors for early mortality to other men but are at higher risk from hyperinsulinaemia, hyperglycaemia, and high mean corpuscular volume.     

PHYLOGENETIC ANALYSIS AND GENOME SIZE OF OSTREOCOCCUS TAURI (CHLOROPHYTA, PRASINOPHYCEAE)

Ostreococcus tauri Courties et Chrétiennot-Dinet is the smallest described autotrophic eukaryote dominating the phytoplanktonic assemblage of the marine Mediterranean Thau lagoon (France). Its taxonomic position was partly elucidated from ultrastructure and high-pressure liquid chromatography (HLPC) pigment analysis. The sequence analysis of the 18S rDNA gene of O. tauri measured here is available in EMBL Nucleotide Sequence Database (accession number: Y15814) and allowed to clarify its phylogenetic position. O. tauri belongs to the Prasinophyceae and appears very close to Mantoniella, a typical scaly Prasinophyceae, morphologically very different from the naked and coccoid Ostreococcus. An electrophoretic analysis of O. tauri shows that the nucleus contains 10.20 mbp. This small genome, fragmented into 14 chromosomes ranging in size from 300 to 1500 kbp, confirms the minimalist characteristics of Ostreococcus tauri.     

Functional Effects of Adiponectin on Endothelial Progenitor Cells

Adiponectin is an adipokine whose plasma levels are inversely correlated to metabolic syndrome components. Adiponectin protects against atherosclerosis and decreases risks in myocardial infarction. Endothelial progenitor cells (EPCs) are a heterogeneous population of circulating cells involved in vascular repair and neovascularization. EPCs number is reduced in patients with cardiovascular disease. We hypothesize that the positive effects of adiponectin against atherosclerosis are explained in part by its interactions with EPCs. Cells were obtained from healthy volunteers' blood by mononuclear cell isolation and plating on collagen‐coated dishes. Three sub‐populations of EPCs were identified and characterized using flow cytometry. EPCs' expression of adiponectin receptors, AdipoR1, and AdipoR2 was evaluated by quantitative PCR. The effects of recombinant adiponectin on EPCs' susceptibility to apoptosis were assessed. Finally, expression of neutrophil elastase by EPCs and activity of this enzyme on adiponectin processing were assessed. Quantitative PCR analysis of EPCs mRNAs showed that AdipoR1 mRNA is expressed at higher levels than AdipoR2. Expression of AdipoR1 protein was confirmed by western blot. Adiponectin significantly increased survival of two sub‐populations of EPCs in conditions of serum deprivation. Such effect could not be demonstrated in the third EPCs sub‐population. We also demonstrated that EPCs, particularly one sub‐population, express neutrophil elastase. Neutrophil elastase activity was confirmed in EPCs' conditioned media. Adiponectin protects some EPCs sub‐populations against apoptosis and therefore could modulate EPCs ability to induce repair of vascular damage. Neutrophil elastase activity of EPCs could locally modulate adiponectin activity by its involvement in the generation of the globular form of adiponectin.     

Prostaglandins involvement in the formation of luteinized unrupted follicles in the cyclic female rat

The purpose of this investigation was to study the role played by prostaglandins in advanced ovulation and in the formation of luteinized unrupted follicles (LUF) in cyclic female rats. Dose related effects on ovulation were observed in rats given LH on diestrus 2 at 16.30. A significant positive correlation was observed between the number of postovulatory corpura lutea (POCL) and the increasing doses of LH. By contrast the number of LUF was negatively correlated with LH. Indomethacin treatment by 6h30 after administration of an ovulatory LH dose significantly increased the occurence of LUF at the expense of POCL. Conversely PGF_2α when admiststered by 6h30 after a subovulatory LH stimulation enhanced in a dose dependent manner the number of POCL with respect to the LH treated controls. Under a similar treatment with a subovulatory dose of LH, PGE₂ remained without ovulatory effects. The mechanisms of the formation of LUF are discussed on the basis of these results.     

Physico-chemical investigation of the mode of binding of the alkaloids 5,6-dihydroflavopereirine and sempervirine with DNA

The mode of binding of 5,6-dihydroflavopereirine and sempervirine to DNA has been investigated by absorption spectrophotometry, circular and electric linear dichroism, fluorescence and fluorescence polarization, viscosity increase of sonicated linear DNA and circular DNA unwinding. Although the spectroscopic properties of both compounds bound to DNA resembled those reported in our previous study of DNA complexes with two other alkaloids, and observed with planar intercalating compounds, only sempervirine was able to unwind circular DNA. The latter drug however showed signs characteristic of aggregation at the surface of the polyion. The differences between the behaviours of the four alkaloids so far investigated by us are interpreted on the basis of different extent of penetration of the chromophore ring into the DNA helix.