Effects of naftidrofuryl on hypoxia-induced activation and mortality of human endothelial cells.

The present study was designed to elucidate the possible beneficial effects of naftidrofuryl on ischemia-induced endothelium damage. For this purpose, an in vitro model was developed wherein human endothelial cells isolated from umbilical vein were submitted to hypoxia. Long-term hypoxia incubation (6 h) induced cell mortality, and naftidrofuryl strongly protected endothelial cells against this mortality in a dose-dependent manner and at concentrations as low as 10(-9) M.

Hypoxia-induced activation of endothelial cells as a possible cause of venous diseases: hypothesis.

Blood stasis in leg veins is a situation commonly linked to the development of venous diseases such as varicoses. Such a stasis will provoke an ischemia, thus decreasing oxygen availability to tissues. Owing to its localization between blood and tissue, endothelium is the first target of this insult.

Increased PMN adherence on endothelial cells after hypoxia: involvement of PAF, CD18/CD11b, and ICAM-1.

Ischemia is a well-known situation occurring in several diseases. There is a large body of evidence for the accumulation of neutrophils in the microvascular injury and the transformation of ischemic tissue into an inflammatory territory. However, the molecular mechanisms underlying this phenomenon are still poorly understood.

Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia.

In ischemic organs, arachidonic acid (AA) metabolites and mostly prostaglandins (PGs) have been found to be released in high amounts. The mechanism for this AA metabolism activation and its physiological implications are not clear. Because endothelial cells are an important source of PGs and because they seem to be very rapidly affected by ischemia, we developed an in vitro model where human endothelial cells were submitted to hypoxia.

[Diagnostic modalities and treatment of cancer of the pancreas. Evolution in the population in the department of Côte d'Or from 1976 to 1988].

There is no study establishing time trends for the diagnostic and therapeutic approaches to pancreatic cancer based on population data. The data of the Registry of Digestive Tumors of Côte-d'Or (France) were used to this end in 544 cancers diagnosed between 1976 and 1988. The proportion of the histologically confirmed cases increased annually by 13.

Human umbilical vein endothelial cells submitted to hypoxia-reoxygenation in vitro: implication of free radicals, xanthine oxidase, and energy deficiency.

Ischemia-reperfusion is observed in various diseases such as myocardium infarct. Different theories have been proposed to explain the reperfusion injury, among them that the free radical generation plays a crucial role. To study the mechanisms of the reperfusion injury, a hypoxia (H)-reoxygenation (R) model upon human umbilical vein endothelial cells in culture was developed in order to mimic the in vivo situation.

Importance of various antioxidant enzymes for cell stability. Confrontation between theoretical and experimental data.

A theoretical model was developed taking into account the production and destruction of oxygen-derived free radicals. The steady state of the system was derived by using the rate equations of these reactions, and the stability of the system was tested. In the simplified model, only one stable steady state was found.

Effect of hypoxia upon intracellular calcium concentration of human endothelial cells.

Ischemia is a situation occurring in several diseases including myocardial infarction and organ transplantation in which oxygenated blood supply is impaired. Ischemia leads to many cellular and tissue modifications, the most important one being cell death. Several explanations have been proposed to account for these modifications and cell death; among them is calcium overload.

[Epidemiology and prevention of colorectal cancer].

Colorectal carcinoma is very common in western countries. It is in the front line of malignant pathology in France. The estimated number of new cases is almost 26,000 per year.

[The relation between venous stasis and the occurrence of pain].

Venous stasis is a situation encountered commonly in varicose disorders. The potential implications of this decrease in oxygen levels in terms of the status of the cells of the vein were assessed. When endothelial cells are subjected to hypoxia, there is stimulation of the cells which shows itself as increased synthesis of prostaglandins and of PAF (Platelet Activating Factor).

The importance of antioxidant enzymes in cellular aging and degeneration.

Aerobic cells contain various amounts of the three main antioxidant enzymes: superoxide dismutase (SOD), catalase and GSH peroxidase. These three enzymes are necessary for cell survival since inhibition of their activity leads to the arrest of cell mitosis and to cell death. Amongst them, GSH peroxidase was shown to be more efficient than catalase and much more than SOD.

[A comparative study of the protective effect of different phlebotonic agents on endothelial cells in hypoxia].

Numerous reported findings indicate that the etiology of venous diseases is multifactorial. One of the chief factors is certainly stasis of blood in the veins of the lower limbs during long periods spent standing up. This stasis causes tissue hypoxia which first affects the venous wall.

[A comparative study of the protective effect of various phlebotonic agents on hypoxic endothelial cells].

Many findings indicate that the etiology of venous disease is multifactorial. One of the chief factors is certainly the stasis of blood in the lower limbs during long periods of standing. This stasis causes tissue hypoxia which first affects the venous wall.

Cytotoxicity of linoleic acid peroxide, malondialdehyde and 4-hydroxynonenal towards human fibroblasts.

Lipid peroxidation occurs during oxidative stress and leads to the formation of various active compounds. However, controversy remains about its importance in the events leading to cell death. One approach to estimate their role in cell death would be to test the toxicity of oxidative products generated during the stress.

Association of antioxidant systems in the protection of human fibroblasts against oxygen derived free radicals.

The protection of human diploid fibroblasts against high oxygen tension was investigated using various combinations of the three major antioxidant enzymes: superoxide dismutase, catalase and glutathione peroxidase. alpha-Tocopherol, a well-known hydrophobic antioxidant, was also tested in combination with the different enzymes. Microinjection of solutions containing different combinations of the three enzymes was compared with the injection of each single enzyme.

Comparative study of oxygen toxicity in human fibroblasts and endothelial cells.

The resistance of human pulmonary fibroblasts (WI-38) and human umbilical vein endothelial cells to oxygen toxicity (1 atm O2) was compared. Endothelial cells were more sensitive than fibroblasts. They contained also less antioxidant enzymes except for SOD: respectively 132%, 96%, 70%, 59%, and 21% of the SOD, GSH peroxidase, GSH reductase, catalase, and G6PD content of fibroblasts.

[Behavior of human endothelial cells in hyperoxia and hypoxia: effect of Ginkor Fort].

Recent discoveries have shown that venous diseases have a multifactorial etiology. One of the factors which is definitely involved in this pathologic process is the change in the concentration of oxygen. An increase in the concentration of oxygen, hyperoxia, or reoxygenation following hypoxia, damages the tissues by stepping up the production of free radicals.

Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals.

Glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase are the most important enzymes of the cell antioxidant defense system. However, these molecules are themselves susceptible to oxidation. The aim of this work was to estimate to what extent this system could be inactivated by its own substrates.

Respiratory activity of isolated rat liver mitochondria following in vitro exposure to oxygen species: a threshold study.

Respiratory activity of isolated rat liver mitochondria was assayed following in vitro exposure to oxygen radicals. Our results show that mitochondrial respiration is more sensitive to O2.(-) than to H2O2.

Importance of a threshold for error accumulation in cell degenerative processes. I. Modulation of the threshold in a model of free radical-induced cell degeneration.

Antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) have been injected into human fibroblasts exposed to 2 atm O2 in order to test if the threshold of oxidative damage versus antioxidant defenses could be modulated and if the damage remains reversible beyond the threshold. Cell damage was estimated by thymidine incorporation and cell survival curves. The proportion of dividing cells, measured by thymidine incorporation, rapidly decreased after O2 incubation: no cells could divide after 15 h of hyperoxia.

Quantitative study of natural antioxidant systems for cellular nitrofurantoin toxicity.

The toxicity of nitrofurantoin was studied on human WI-38 fibroblasts: this chemical was lethal when added at concentrations higher than 5.10(-5) M in the culture medium. The protection afforded by antioxidants was then tested: alpha-tocopherol gave at 10(-4) M a light protection in contrast to ascorbic acid which even became toxic at high concentrations.

Microinjection of antibodies against superoxide dismutase and glutathione peroxidase.

Antibodies were prepared against glutathione peroxidase, superoxide dismutase, and catalase. Inhibition of the enzyme activity was obtained with anti-Gpx and anti-SOD antibodies but not with anti-CAT antibodies. The antibodies were then injected into human fibroblasts and bovine chondrocytes in culture either under normal conditions or under 1 atm of oxygen.

Use of the inhibition of enzymatic antioxidant systems in order to evaluate their physiological importance.

Chemical inhibitors of the different antioxidant enzymes were systematically testet either on purified enzymes of after incubation with human fibroblasts in culture. Inhibition values were obtained for catalase with aminotriazole, for superoxide dismutase with diethyldithiocarbamate, for glutathione peroxidase with mercaptosuccinate, for glutathione reductase with bischloroethylnitrosourea and for glutathione synthesis with buthionine sulfoximine. Viability of cells incubated with these inhibitors was then tested under normal conditions and under high oxygen pressure; the data were correlated with the above-mentioned inhibitory values.