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Biomedical subjects

F Roux

Publications and source records attributed to F Roux.

At least 55 records · Page 3Linked to original sources
PubMed1996

Ethanol potentiates lipopolysaccharide- or interleukin-1 beta-induced nitric oxide generation in RBE4 cells.

Our present study investigated the effects of ethanol treatment on inducible nitric oxide (NO) synthase pathway from lipopolysaccharide- or interleukin-1 beta-treated cultured rat blood-brain barrier cell line (rat brain endothelial 4 cells: RBE4 cells). Cells were lipopolysaccharide- or interleukin-1 beta-treated with or without ethanol (50, 100 or 200 mM) for 16 or 24 h. Inducible NO synthase activity and mRNA expression were measured using Griess reaction and reverse transcription-polymerase chain reaction (RT-PCR) respectively. In the absence of lipopolysaccharide or interleukin-1 beta, ethanol treatments failed to stimulate inducible NO synthase gene expression. Lipopolysaccharide or interleukin-1 beta increased nitrite production and inducible NO synthase mRNA levels, and ethanol potentiated this effect. We concluded that ethanol could aggravate the consequences of NO generation by RBE4 cells after inducible NO synthase induction following inflammation or sepsis. This ethanol action on NO generation could contribute to circulatory failure associated with shock due to sepsis or hemorrhage, and alter blood-brain barrier permeability.

Animals↗
PubMed1996

Synergistic stimulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities by retinoic acid and astroglial factors in immortalized rat brain microvessel endothelial cells.

The immortalized rat brain microvessel endothelial cell line RBE4 was used to investigate the in vitro regulation of two blood-brain barrier specific enzymes, gamma-glutamyl transpeptidase (GTP) and alkaline phosphatase (ALP). The effects of bFGF, astroglial factors, and retinoic acid (a cell differentiation agent) on GTP and ALP activities were separately or simultaneously studied in order to define optimal culture conditions for induction of these two specific enzymes of the blood-brain barrier. In the present study, a phenotypically distinct subpopulation of endothelial cells has been shown to develop from confluent cobblestone monolayers of RBE4 immortalized cerebral endothelial cells. These distinct cells were present within multicellular aggregates and specifically exhibited GTP and ALP activities. Addition of bFGF, astroglial factors, or retinoic acid induced the formation of these three-dimensional structures and in consequence an increase in GTP and ALP activities. For retinoic acid and astroglial factors, this increase could also be explained by the stimulation of either GTP or ALP expression in the phenotypically distinct positive cells associated with aggregates. Simultaneous treatment with retinoic acid and astroglial factors had a synergistic effect on GTP and ALP expression and thus may allow these distinct cells to evolve toward a more differentiated state. Since such results were also obtained with physiological concentrations of retinoic acid, we suggest that addition of this agent might contribute to greater differentiation of cells in in vitro blood-brain barrier models where endothelial cells are cocultured with astrocytes.

Alkaline Phosphatase↗
PubMed1996

Effect of anoxia and reoxygenation on antioxidant enzyme activities in immortalized brain endothelial cells.

The effects of anoxia and reoxygenation on major antioxidant enzyme activities were investigated in vitro in immortalized rat brain endothelial cells (RBE4 cells). A sublethal anoxic period of 12 h was assessed for RBE4 cells using the neutral red uptake test. Anoxia markedly influenced the specific activity of catalase and superoxide dismutase, with no major effect on glutathione peroxidase or glutathione reductase. After 24 h postanoxia, the superoxide dismutase activity modulated by the presence or absence of oxygen returned to control value. Damage and recovery of RBE4 immortalized rat brain endothelial cells in culture after exposure to free radicals and other oxygen-derived species provides a useful in vitro model to study anoxia-reoxygenation trauma at the cellular level.

Animals↗
PubMed1996

Treatment by iodized oil (Lipiodol UF) of a population in Mali suffering from endemic goiter.

In order to reduce the prevalence of goiter in a village of Mali liable to iodine deficiency, an iodized product (Lipiodol Ultra Fluide) was orally administered to their inhabitants. Taking into account a series of demographic variables and goiter types, a protocol was conducted using Lipiodol at three different dosage levels. Six months after the treatment, the hormone levels regained normal values, whereas only the smallest dose reduces the volume of goiters significantly.

Female↗
PubMed1996

Functional expression of P-glycoprotein in an immortalised cell line of rat brain endothelial cells, RBE4.

The presence of P-glycoprotein in the cell plasma membrane limits the penetration of many cytotoxic substances into cells that express the gene product. There is considerable evidence also to indicate that P-glycoprotein is expressed as part of the normal blood-brain barrier in the luminal membranes of the cerebral capillary endothelial cells, where it presumably performs a protective function for the brain. This report describes the functional expression of P-glycoprotein in an immortalised cell line, RBE4, derived from rat cerebral capillary endothelial cells. The expression of P-glycoprotein is demonstrated by western immunoblotting and by immunogold and fluorescent staining with monoclonal antibodies. The cellular accumulation of [3H]colchicine and [3H]-vinblastine is investigated and shown to be enhanced by the presence of azidothymidine, chlorpromazine, verapamil, cyclosporin A, and PSC 833 ([3'-keto-Bmt1]-[Val2]-cyclosporin) at 50 or 100 microM concentration. It is concluded that the RBE4 cell line is a valuable tool for investigating the mechanisms of P-glycoprotein activity both in the blood-brain barrier and in multidrug resistance in general.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Hypercalcitoninemia in conditions other than medullary cancers of the thyroid].

Serum calcitonin (CT) assays are the most useful tumoral marker for the diagnosis and follow up of medullary thyroid carcinoma (MTC). Since 1988 the sensitivity and specificity of CT assays have been considerably improved. Normal basal and pentagastrin (Pg) stimulated CT ranges remain to be established and it appears necessary to determine the pathological circumstances which may be responsible for hypercalcitoninemia in addition to MCT. By reviewing literature and data from the "Groupe d'Etude des Tumeurs à Calcitonine": a/we compared basal and Pg stimulated CT values obtained with two commercially available immunometric CT assays and we observed that CT values measured by the CT-EASIA MEDGE-NIX kit were three fold the values obtained by suing the hGH ELSA CIS BIOINDUSTRIE Kit; b/we determined that hypercalcitoninemia may be observed in isolated C Cell Hyperplasia (HCC) surrounding either lymphocytic thyroiditis or follicular thyroid carcinoma loci, in chronic renal failure on maintenance hemodialysis, and in various neuroendocrine tumors. Surprisingly, the hypercalcitoninemia related to HCC has been found in genetically unaffected members (without any identified gene RET mutation) of both a Multiple Endocrine Neoplasia type 2A and isolated familial hereditary MTC.

Calcitonin↗
PubMed1995

Serum erythropoietin and reticulocyte maturity index after renal transplantation: a prospective longitudinal study.

Improvement in erythropoiesis following renal transplantation (RT) was assessed in 74 consecutive patients by serial measurements of serum erythropoietin (EPO), hematocrit, absolute reticulocyte count (ARC) and serum creatinine during the first month after RT. The reticulocyte maturity index (RMI) which provides an objective measure of red-cell maturity was assessed in 31 patients by flow cytometry using thiazole orange. In group I (n = 39) with immediate graft function, EPO levels increased rapidly from day 2 and remained elevated at the plateau between two and three times the upper limit of normal during the first 2 months. In group II (n = 29) with delayed graft function, EPO levels increased gradually from day 10 when renal function improved significantly. No particular significant biphasic pattern of secretion was detected in group I or II. In both groups, hematocrit rose to over 35% approximately 3 months after RT. In a third group (n = 6) with immediate postoperative acute blood loss and severe anemia, a hematocrit fall was followed by a steep increase in EPO levels with a negative correlation between hematocrit and EPO levels during the first 4 days. During acute rejection, EPO diminished significantly by more than 50% either on the day of diagnosis or on the following days in 8 patients. RMI increased by 25% over the pretransplantation values by 7 days on average before the ARC rose. Thus the RMI seems to be an early sensitive predictor of erythropoiesis after RT. EPO response after RT depends on graft function, and the early transient increase in EPO observed in patients with acute blood loss may explain the apparent biphasic response previously reported.

Adolescent↗
PubMed1995

Role of 1,2-sn diacylglycerol in airway smooth muscle stimulated by carbachol.

Activation of muscarinic receptors in airway smooth muscle leads to breakdown of membrane polyphosphoinositides. In agreement with others, we show here that muscarinic stimulation elicits inositol-1,4,5-triphosphate formation. In addition, we show that carbachol also elicits total diacylglycerol and 1,2-sn diacylglycerol accumulation in a specific and dose-dependent manner (EC50 values: 2.1 x 10(-8) M for 1,2-sn diacylglycerol). The time-course of inositol-1,4,5-triphosphate accumulation is compatible with that of the clonic phase of muscle contraction. Since this derivative can mobilize intracellular Ca2+ stores, it may play a second-messenger role in the initial phase of contraction. The time-course of diacylglycerol accumulation is compatible with the muscarinic-induced tonic phase of smooth-muscle contraction. Carbachol induces similar dose-dependent reductions in isoproterenol-induced muscle relaxation (EC50 values for relaxation concentration-response curves to isoproterenol: 3 x 10(-6) M and 2.1 x 10(-5) M, with carbachol at 10(-7) M and 10(-4) M, respectively), and increases in adenylate cyclase activity (EC50 values for the concentration-response to isoproterenol: 1.2 x 10(-6) M and 1.5 x 10(-5) M, with carbachol at 10(-7) M and 10(-4) M, respectively). Since it is known that carbachol-induced uncoupling of beta 2-adrenergic receptors is proportional to the breakdown of polyphosphoinositides, and that 1,2-sn diacylglycerol is a potent activator of protein kinase C, 1,2-sn diacylglycerol could be mediating the uncoupling of beta 2-adrenergic receptors, via activation of alpha-protein kinase C and subsequent phosphorylation of receptor, and/or cyclase, and/or G proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1995

Abnormal calcitonin basal levels and pentagastrin response in patients with chronic renal failure on maintenance hemodialysis.

Hypercalcitoninemia has been reported in renal failure. Using a specific monomeric calcitonin (CT) immunoassay, we measured CT levels in 154 hemodialyzed patients. The relationship between CT and serum intact parathyroid hormone (PTH), gastrin, alkaline phosphatases, phosphate and calcium was studied. The pentagastrin test was performed in 26 patients exhibiting basal hypercalcitoninemia. Basal CT levels over 5.7 pmol/l (20 ng/l) were found in 25.3% of the patients and values higher than 26 pmol/l (90 ng/l) in 7.8%. Although CT is cleared by hemodialysis, post-dialysis CT levels either were unchanged or increased as compared with pre-dialysis values. This suggests that hypercalcitoninemia is not related to a decreased renal clearance, and that hemodialysis induces a specific regulatory pathway. None of the parameters studied were found to explain high CT levels. Of the patients with hypercalcitoninemia, 11.5% exhibited abnormal CT response to pentagastrin but no relationship between CT and phosphate, calcium and PTH levels was evidenced. Our findings confirm high CT monomer levels in renal failure. As there was no correlation with parameters classically involved in CT regulation, its physiological significance remains unclear. Abnormal CT response to pentagastrin raises the problem of its specificity as a tumoral marker with regard to medullary thyroid carcinoma.

Adolescent↗
PubMed1995

[Single-lung transplant in chronic obstructive disease].

The feasibility and the good immediate acceptability of unilateral lung transplants in the patients with obstructive respiratory problems have recently been demonstrated and since the initial reports, some hundreds of lung transplants have been performed in various parts of the world for this indication. Nevertheless, few results of respiratory function are currently available in the medium term. We report these in a series of 20 patients with severe obstruction who were given single lung transplants. The actual probability of survival for 1 and 2 years was 75 and 70% respectively with 4 peri-operative deaths and 2 later deaths. In the 16 survivors of more than 6 months, in relation to the pre-operative values, a significant improvement was observed 3 months after the graft in the FEV1 which rose from 17 +/- 6 to 53 +/- 13% of the predicted values. The PaO2 rose from 52 +/- 10 to 81 +/- 3 mmHg. The distance covered on the six minute walking test went from 99 +/- 84 m before the graft to 587 +/- 147 m 6 months after the operation. In addition to the improved distance, the lung function was stable in a group of patients as the months went by, although there was a fall in the respiratory function in others with the appearance of the syndrome of bronchiolitis obliterans or in 2 patients with bronchial complications. The four patients with severe deterioration in the graft function were re-transplanted with a good clinical result in three of them, the fourth dying in the immediate post-operative period. We conclude that single lung transplant represents an effective treatment both in the short and medium term in patients with chronic airflow obstruction.

Adult↗
PubMed1995

[Prognostic value of pre-therapeutic levels of carcino-embryonic antigen in primary bronchial carcinoma].

To evaluate the pronostic value of an elevated seric carcinoembryonic antigen (CEA > 10 ng/ml) at diagnosis, in patients with lung cancer, a pair study was done: couples of patients with same staging and histologic type were established, one patient with high CEA level compared to one patient with normal CEA level (< 5.5 ng/ml). Other markers were measured: neuron specific enolase (NSE), squamous cell carcinoma (SCC) or Cyfra 21-1. Survival was the end point of comparison. For 89 couples created, patients with low CEA level had a better survival rate at one year ( p = 0.02), this prognosis advantage was confirmed by a comparison of survival curves with Mantel-Cox and Breslow test (p = 0.01), but not by the signs test. These differences were also observed for the 71 couples of squamous cell carcinomas and adenocarcinomas, and the apparied signs test was still not significant. The poor prognosis persisted for patients with high CEA level, when one another marker's level (NSE or SCC or Cyfra 21-1) was increased, in comparison with patients with any marker increased. On 29 couples of all histological subtypes or on the 25 couples of non small cell lung cancer, the signs test and the comparison of survival curves were significant, but not the 1 year survival rate. This study shows that a CEA level greater than 10 ng/ml at diagnosis is a poor pronostic factor in patients with lung carcinoma, independent of the stage of disease and of the histologic type.

Antigens, Neoplasm↗
PubMed1994

Regulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities in immortalized rat brain microvessel endothelial cells.

Rat brain microvessel endothelial cells were immortalized by transfection with a plasmid containing the E1A adenovirus gene. One clone, called RBE4, was further characterized. These cells display a nontransformed phenotype and express typical endothelial markers, Factor VIII-related antigen and Bandeiraea simplicifolia binding sites. When RBE4 cells were grown in the presence of bFGF and on collagen-coated dishes, confluent cultures developed sprouts that extend above the monolayer and organized into three-dimensional structures. The activity of the blood-brain barrier-associated enzyme, gamma-glutamyl transpeptidase (gamma GTP), was expressed in these structures, not in the surrounding monolayer. Similar results were obtained with the microvessel-related enzyme alkaline phosphatase (ALP). Addition of agents that elevate intracellular cAMP reduced the formation of three-dimensional structures, but every cell inside the aggregates still expressed gamma GTP and ALP activities. Such structures, associated with high levels of gamma GTP and ALP activities, were also induced by astroglial factors, including (1) plasma membranes from newborn rat primary astrocytes or rat glioma C6 cells, (2) C6 conditioned media, or (3) diffusible factors produced by primary astrocytes grown in the presence of, but not in contact with RBE4 cells. RBE4 cells thus remain sensitive to angiogenic and astroglial factors for the expression of the blood-brain barrier-related gamma GTP activity, as well as for ALP activity, and could constitute the basis of a valuable in vitro model of the blood-brain barrier.

Alkaline Phosphatase↗
PubMed1994

Plasma endothelin in haemodialysis patients treated with recombinant human erythropoietin.

Predialysis plasma endothelin (ET) values were followed during the first 8 weeks of rHuEpo treatment in 12 patients on routine haemodialysis. Mean plasma ET was significantly increased in uraemic patients before rHuEpo (27.9 +/- 11.4 pmol/l), as compared to 40 healthy controls (16.5 +/- 5.7 pmol/l) (P < 0.0001). Under rHuEpo treatment, predialysis values remained unchanged although diastolic blood pressure increased after 2 and 6 weeks. We found no correlation between ET and haemoglobin or blood pressure before or under rHuEpo treatment. These results confirmed the high levels of plasma ET in haemodialysis patients, but no increase was observed during rHuEpo treatment.

Adult↗
PubMed1993

Nitric oxide and endothelin secretion by brain microvessel endothelial cells: regulation by cyclic nucleotides.

Endothelin (ET)-1 was originally characterized as a potent vasoconstrictor peptide secreted by vascular endothelial cells. It possesses a wide range of biological activities within the cardiovascular system and in other organs, including the brain. Also secreted by endothelial cells, nitric oxide (NO), has recently been identified as a relaxing factor, as well as a pleiotropic mediator, second messenger, immune defence molecule, and neurotransmitter. Most of the data concerning the secretion of these two agents in vitro has been collected from studies on macrovascular endothelial cells. Given the remarkable heterogeneity of endothelia in terms of morphology and function, we have analyzed the ability of brain microvessel endothelial cells in vitro to release ET-1 and NO, which, at the level of the blood-brain barrier, have perivascular astrocytes as potential targets. The present study was performed with immortalized rat brain microvessel endothelial cells, which display in culture a non transformed phenotype. Our data demonstrate that: (1) these cells release NO when induced by IFN gamma and TNF alpha, (2) they constitutively secrete ET-1, and (3) cAMP potentiates the cytokine-induced NO release and exerts a biphasic regulation on ET-1 secretion: micromolar concentrations of 8-Br-cAMP inhibit and higher doses stimulate ET-1 secretion. This stimulation is blocked by EGTA and the calmodulin antagonist W7, but not by protein kinase C inhibitors, suggesting the involvement of the calmodulin branch of the calcium messenger system. These results suggest that cerebral microvessel endothelial cells may participate in vivo to the regulation of glial activity in the brain through the release of NO and ET-1.

Amino Acid Oxidoreductases↗