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Biomedical subjects

V Robert

Publications and source records attributed to V Robert.

At least 55 records · Page 3Linked to original sources

Different regulation of cardiac and renal corticosteroid receptors in aldosterone-salt treated rats: effect of hypertension and glucocorticoids.

This study analysed the regulation of cardiac mineraloreceptor (MR) and glucoreceptor (GR) in aldosterone-salt treatment (AST). AST causes hypertension, left ventricle (LV) hypertrophy and decreases plasma corticosterone level. Ribonuclease protection assay and Western blot analysis showed a rise of MR mRNA (1.5- and 1.4-fold at day 15 and 30, respectively) and protein levels (1.8- and 4.1-fold at day 30 and 60, respectively) in the LV, but not in either the right ventricle (RV) or in kidney of treated rats. Addition of MR antagonist spironolactone (20 mg/kg/day) for 30 days failed to prevent these changes but was able to reduce AST-induced cardiac fibrosis. Similar hypertension-induced MR upregulations were observed in the LV of AngII-hypertensive rats and of 12-week-old SHR when compared to 4-week-old prehypertensive SHR. AST also enhanced left ventricular GR mRNA (2.0- and 3.0-fold at day 7 and 15, respectively) and protein contents (2.0- and 1.7-fold at day 30 and 60, respectively). In contrast to MR, GR levels were also upregulated in both RV and kidney. Such an upregulation was equally observed at mRNA and protein levels in LV, RV and kidney after adrenalectomy (15 days) and was prevented in both tissues after glucocorticoid replacement (adrenalectomy + dexamethasone at 100 micro g/kg/day for 15 days). Therefore, MR level may be controlled by hemodynamical factors whereas that of GR depends upon glucocorticoids level.

Adrenalectomy↗

High heterogeneity in the number of Plasmodium falciparum gametocytes in the bloodmeal of mosquitoes fed on the same host.

To investigate the quantitative distribution of Plasmodiumfalciparum gametocytes into the vector bloodmeal, Anopheles arabiensis mosquitoes were fed on 3 volunteers naturally infected with gametocytes. The content of each mosquito midgut was smeared on a microscope slide and Giemsa stained. The distribution of gametocytes ingested by mosquitoes followed a negative binomial distribution, with apparently constant overdispersion (parameter k +/- S.E. = 3.105 +/- 0.392) for the 3 series. This aggregation of gametocytes in some midguts probably facilitates the conjunction of gametes and fertilization. This suggests that P. falciparum gametocytes in the peripheral blood flow of infected man do not follow an independent, homogeneous pattern but show a significant aggregation.

Adult↗

Anti-NANP antibody and treatment efficacy in patients with acute uncomplicated falciparum malaria attacks.

African patients originating from the hypoendemic, urban area of Greater Dakar (Senegal, West Africa) who presented with an acute Plasmodium falciparum infection were studied using an in-vivo chloroquine sensitivity assay for 28 days. Forty-seven patients with acute malaria infections were treated with 25 mg/body weight of chloroquine. Adequate responses to treatment were observed in 24 patients (51%), whereas 23 (49%) were resistant. On the day of admission, these two groups of patients were comparable with respect to age, level of parasitemia and delay before initiation of treatment, but not with respect to gametocyte prevalence which was higher in patients resistant to therapy (48%) than in those who responded to treatment (17%). In order to evaluate whether the therapeutic response was associated with any given specific immune response, antibody activities against different stages of the parasite cycle were evaluated: anti-NANP repeats (i.e. antisporozoite stage antigen), anti-Pfs 45 kDa (i.e. antigametocyte stage antigen), and anti-MSP3 (i.e. antimerozoite stage antigen) antibodies were measured by ELISA at day 0 (i.e. on the day of admission and before initiation of treatment), day 7 and day 28. No significant differences between treatment-sensitive and treatment-resistant infections were observed for antibody prevalences and optical densities, except at day 0, when the prevalence of antibodies against NANP repeats was 2.4 times more frequent in the group of patients with a propitious response to treatment: 62.5% of the patients with an infection sensitive to chloroquine had anti-NANP antibodies, whereas only 26.1% of the patients resistant to chloroquine treatment had such a humoral response. These observations are discussed in relation to (1) the finding that gametocyte prevalence was markedly increased at a time when resistance to antimalarial treatment was observed; (2) the possibility that the efficacy of the therapeutic response could be the result of the combined effects of treatment and the individual immune status of the patients at the time of drug cure; and (3) the presence of detectable anti-NANP activity as potential indicator of the level of premunition acquired in an area of low and seasonal malaria transmission.

Adolescent↗

Cardiac aldosterone production and ventricular remodeling.

An intracardiac production of aldosterone has been recently reported in rat. This production is increased both acutely and chronically by angiotensin II, observations suggesting that the heart contains a steroidogenic system that is regulated similarly to the adrenal one. Cardiac production of aldosterone is small compared with that of the adrenal, raising the question of its function in normal conditions. Moreover, the regulation of this synthesis in pathophysiologic states remains unknown. In an analysis of the effects of a one-month myocardial infarction (MI) on the cardiac steroidogenic system, it was observed that aldosterone-synthase mRNA and the aldosterone concentration were increased by 2- and 3.5-fold, respectively, in the noninfarcted part of the rat left ventricle. MI also induced a 1. 9-fold increase in the cardiac angiotensin II level. Losartan prevented these changes, and the MI-induced collagen deposition in noninfarcted area of the left ventricle was reduced by 1.6- and 2. 5-fold by both spironolactone and losartan treatments, respectively. Thus, these observations indicate that MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This activation is mediated by cardiac angiotensin II via the angiotensin II type 1 (AT1) receptor, and the resultant increase of intracardiac aldosterone level may be involved in post-MI ventricular remodeling.

Aldosterone↗

High frequency in esophageal cancers of p53 alterations inactivating the regulation of genes involved in cell cycle and apoptosis.

Somatic mutations of the tumor suppressor gene p53 have been frequently detected in esophagal cancers, but their biological significance remains to be established. The tumor suppressor activity of p53 results in part from its ability to transactivate genes involved in the cell cycle and apoptosis, such as p21, bax and PIG3, and some p53 mutations may have a differential effect on the transactivation of these target genes. We developed yeast strains in which the activation by wild-type p53 of reporter plasmids containing p53 binding sites present within these target genes induces a change in the color of the colonies (red/white). Using these strains, we analyzed 56 esophageal cancers from patients residing in Normandy, France, a high incidence geographic area. Forty-seven tumors (84%), scored as mutant with the p21, bax and PIG3 reporter strains and in most of the cases (76%), the percentage of red colonies suggested that both p53 alleles were inactivated. Sequencing analysis allowed the identification of a p53 mutation in each positive sample, and the spectrum of mutations was in agreement with the etiological role of tobacco and alcohol. These results confirm the high frequency of biallelic p53 mutations in esophageal carcinoma and strongly suggest that their biological consequence is the complete alteration of the transactivation of genes involved in the cell cycle and apoptosis, which indicates that p53 alteration is a key event in esophagus carcinogenesis.

Apoptosis↗

Gametocytemia and infectivity to mosquitoes of patients with uncomplicated Plasmodium falciparum malaria attacks treated with chloroquine or sulfadoxine plus pyrimethamine.

Plasmodium falciparum gametocytemia and its related infectivity for mosquitoes was studied in 115 patients (median age = 18 years, range = 4-45) with simple malaria attacks who lived in the hypoendemic area of Dakar, Senegal. Patients were included in a 28-day in vivo sensitivity test after treatment with chloroquine (CQ, n = 82) or sulfadoxine plus pyrimethamine (SP, n = 33). The prevalence of resistant infections was 58.5% in those treated with CQ and 0% in those treated with SP. The gametocytemia peaked at day 7 after treatment. The maximal gametocyte prevalence was 38.2% in the CQ-sensitive infection group, 89.6% in the CQ-resistant group, and 97.0% in those treated with SP The maximal geometric mean gametocytemia was 2.19/microl in the CQ-sensitive infection group, 29.12/microl in the CQ-resistant group and 85.55/microl in those treated with SP. The period between appearance of the first clinical symptom and treatment was positively related to gametocyte prevalence at days 0 and 2. Experimental infection of wild Anopheles arabiensis using membrane feeders was performed at days 0 and 7, and mosquito infectivity was measured by oocyst detection on the midgut. At day 0, 14.1% of the patients had infected at least 1 mosquito, and at day 7, this value was 38.5%. The mean percentage of infected mosquitoes was 3.2% at day 0 and 12.6% at day 7. At day 7 after treatment with CQ, the relative risk for patients with resistant infections of infecting anophelines was 4.07 higher than in those with sensitive infections. No difference was observed in infectivity for mosquitoes between RI-type resistance and the RII + RIII-type resistance. A sporonticidal effect of SP was observed at day 7 after treatment. These data show that P. falciparum gametocytes and their infectivity for mosquitoes were differentiated according to the drug used, its efficacy, and the duration of symptoms before treatment; they were not dependent on the density of asexual stages. Prompt treatment of malaria cases performed at the beginning of symptoms could limit the spread of resistant parasites.

Acetaminophen↗

[Lung transplantation: indications, techniques and results].

Lung transplantation is proposed for young patients with a severe disease that can be expected to be fatal within less than two or three years. The main indications are chronic respiratory failure induced by chronic obstructive lung disease, cystic fibrosis or pulmonary fibrosis, and severe primary or secondary (Eisenmenger syndrome) pulmonary hypertension. The type of transplantation, determined after an exhaustive work-up ruling out all contraindications, is generally a single lung transplantation if there is no bronchial infection or two-lung transplantation or heart-lung transplantation in case of bronchiectasis or pulmonary artery hypertension. Survival at 1, 3 and 5 years is 72, 57 and 43% respectively. Transplantation improves exercise capacity, quality of life and lung function. It normalizes hematosis in case of chronic respiratory failure and pulmonary hemodynamics in case of pulmonary hypertension. The risk of complications, dominated by infections and rejections, requires careful clinical, functional and endoscopic follow-up. Bacterial infections are frequent during the first weeks. The frequency of opportunistic infections can be reduced by anti-infectious prophylaxis strategies. The rejection can occur as an acute episode, frequent during the first 100 days, or is sometimes asymptomatic. Chronic rejection or obliterating bronchiolitis is the main mid-term complication after lung transplantation and is responsible for the low long-term survival rate with recurrent secondary infections due to frequent bronchial colonization with Pseudomonas aeruginosa. Improved prognosis of lung transplantation requires the development of new immunosuppressive agents with lower risk of infection and chronic rejection observed with current treatments.

Adult↗

Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis.

BACKGROUND: This study analyzed the regulation and the role of the cardiac steroidogenic system in myocardial infarction (MI). METHODS AND RESULTS: Seven days after MI, rats were randomized to untreated infarcted group or spironolactone- (20 and 80 mg x kg-1 x d-1), losartan- (8 mg x kg-1 x d-1), spironolactone plus losartan-, and L-NAME- (5 mg x kg-1 x d-1) treated infarcted groups for 25 days. Sham-operated rats served as controls. In the noninfarcted myocardium of the left ventricle (LV), MI raised aldosterone synthase mRNA (the terminal enzyme of aldosterone synthesis) by 2. 0-fold and the aldosterone level by 3.7-fold. Conversely, MI decreased 11beta-hydroxylase mRNA (the terminal enzyme of corticosterone synthesis) by 2.4-fold and the corticosterone level by 1.9-fold. MI also induced a 1.9-fold increase in cardiac angiotensin II level. Such cardiac regulations were completely prevented by treatment of the infarcted heart with losartan. The MI-induced collagen deposition in noninfarcted LV myocardium was prevented by 1.6-fold by both low and high doses of spironolactone and by 2.5-fold by losartan. In addition, norepinephrine level was unchanged in infarcted heart but was attenuated by both losartan and spironolactone treatments. CONCLUSIONS: MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This increase is mediated primarily by cardiac angiotensin II via AT1-subtype receptor and may be involved in post-MI ventricular fibrosis and in control of tissue norepinephrine concentration.

Aldosterone↗

Metabolic capacity for L-citrulline synthesis from ammonia in rat isolated colonocytes.

Ammonia is present at high concentration in the colon lumen and is considered a colon cancer suspect. Furthermore, ammonia usually eliminated by the liver in the ornithine cycle is considered highly toxic to cerebral function when present in excess in the blood plasma. Therefore, the metabolic pathways involved in ammonia metabolism in colonocytes were studied in the present study. Rat colonocytes were found equipped with low carbamoylphosphate synthase I activity, high ornithine carbamoyltransferase and arginase activities and low argininosuccinate synthase activity. High (10 and 50 mmol/l) NH4Cl concentrations but not low concentrations (1 and 5 mmol/l) were found able to increase respectively 3- and 10-fold the conversion of radioactive L-arginine to L-citrulline. In contrast, very low capacity for L-citrulline conversion to L-arginine is found in colonocytes. It is concluded that an incomplete ornithine cycle is operative in colonocytes which results in ammonia stimulated L-citrulline production. The contribution of this metabolic pathway in relation to ammonia detoxication by colonocytes is discussed.

Ammonia↗

Survival and emergence of immature Anopheles arabiensis mosquitoes in market-gardener wells in Dakar, Senegal.

Anopheles arabiensis is the unique species of the An. gambiae complex observed in the wells dug by market-gardeners in the Dakar area. In order to relate the numbers of immature stages and emerging adults mosquitoes, population measurements were performed in eight wells in which An. arabiensis was the only mosquito species. Mean density of immature stages was measured using two sampling methods, the dipping with a tray by giving 50 dips in each well, and the quadrat with a frame on 2 or 3 m2 in each well. The absolute number of emergent adults was obtained by collecting mosquitoes under net-trap covering entirely each wells. The dipping method was quicker and more operational than quadrat method. Density estimations of larvae at stage I to IV did not significantly differed using dipping or quadrat methods. On the contrary, pupal density was underestimated when measured by dipping. Mosquito nets placed over wells increased significantly emergence rate of adults, thus measurement of emerging mosquitoes was possible only the first day following the net putting up. The total number of immature stages in each well was significantly correlated with the number of emergent mosquitoes. The mean number of mosquitoes emerging daily from one well corresponded to 5% of the total number of immature stages. Stage distribution for larvae I to IV and pupae, estimated by quadrat, was respectively 29%, 28%, 22%, 16% et 5% (total = 100%). Taking account the mean duration of various immature stages and the number of emerging mosquitoes by day, the equation of the survivorship curve from larval hatch (excluded) to emergence included was: y = 427.2-136.8 Log x. Therefore the mean mortality at immature stages was 80% i.e. an emerging rate of 20%. The results of this study, associated with those of previous ones, permit to evaluate the average productivity of malaria vectors in market-gardener wells in the Dakar area.

Agriculture↗

Angiotensin AT1 receptor subtype as a cardiac target of aldosterone: role in aldosterone-salt-induced fibrosis.

This study tests the hypothesis that aldosterone induces cardiac fibrosis through an increase of cardiac angiotensin II (Ang II) AT1 receptor levels, thereby potentiating the fibrotic effect of Ang II by determining the effects of spironolactone and losartan on cardiac fibrosis, AT1 density, and gene expression in aldosterone-salt-treated rats. Fibrosis was quantified by slot blots of collagen I and III mRNA levels and videomorphometry of Sirius red-stained collagen. AT1 receptor density was determined by (125I-Sar1-Ile8)-Ang II competition binding, and AT1 mRNA levels were analyzed by quantitative reverse transcriptase polymerase chain reaction. One month of aldosterone-salt treatment induced a decrease in plasma Ang II and an increase in blood pressure, left ventricular hypertrophy, and ventricular fibrosis. Spironolactone (20 mg/kg per day) and losartan spironolactone (10 mg/kg per day) had no effect on the first 3 parameters. Losartan was as effective as spironolactone in preventing ventricular collagen mRNA increase and fibrosis. Ventricular density of AT1 receptors increased 2-fold and was accompanied by a 3-fold increase in the corresponding mRNA in aldosterone-salt compared with sham-operated rats. Both spironolactone and losartan prevented the elevation of ventricular AT1 density and that of right ventricular AT1 mRNA levels. These results demonstrate that the mechanism by which aldosterone-salt induces cardiac fibrosis involves Ang II acting through AT1 receptors. They also suggest that the cardiac AT1 receptor is a target for aldosterone.

Aldosterone↗

[Role of cardiac aldosterone in post-infarction ventricular remodeling in rats].

Synthesis of aldosterone (Aldo) and corticosterone (B) has been recently reported in rat heart. However, regulation of this synthesis in pathophysiological states remains unknown. Thus, this study aimed to analyze effects of a one-month myocardial infarction (MI) on cardiac steroidogenic system. Levels of terminal enzymes of B (11 beta-hydroxylase: 11 beta H) and aldo (Aldo-synthase: AS) synthesis were assayed by quantitative RT-PCR. Cardiac Aldo and B levels were assessed by celite colum chromatography and radioimmunoassay. MI raised AS mRNA levels by 2.0-fold (p < 0.05) but downregulated that of 11 beta H by 2.4 fold (p < 0.05) in the noninfarcted part of the left ventricle (LV). Cardiac steroids production followed a similar pattern of regulation. Aldo level was increased in MI (319 +/- 85 vs 87 +/- 11 pg/mg of protein in control, p < 0.05) whereas that of B fell (2,412 +/- 318 vs 4,624 +/- 857 pg/mg of protein in control, p < 0.05). MI also induced an 1.9-fold increase in cardiac Ang II level. Such cardiac regulations were prevented by Ang II-AT1 receptor antagonist losartan (8 mg/kg/day) treatment. The Aldo receptor antagonist spironolactone (20 mg/kg/day) had no effect. Plasma Aldo and B, and adrenal 11 beta H and AS mRNA levels were unchanged whatever the treatment. The MI-induced collagen deposition in noninfarcted area of the LV was reduced by both spironolactone and losartan treatments by 1.6- and 2.5-fold, respectively. These data indicate that MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This activation is mediated by cardiac Ang II via AT1 receptor and the resultant increase of intracardiac aldosterone level may be involved in post-MI ventricular remodeling.

Aldosterone↗

[Hepatopulmonary syndrome: physiopathology of impaired gas exchange].

The hepatopulmonary syndrome (HPS) consists of a triad of liver dysfunction, increased alveolar-arterial oxygen gradient and intrapulmonary vascular dilations. The mechanisms of impaired arterial oxygenation are still debated but the multiple inert gases elimination technique and more recently contrast echocardiography, greatly facilitated the investigation of such mechanisms. Subsequently the cause of hypoxemia can be attributed to several mechanisms such as ventilation-perfusion mismatch, right-to-left intrapulmonary shunts and alveolar-to-capillary diffusion defect, variously implicated in the severity of the disease. SHP may result from intrapulmonary vascular dilations and angiogenesis but the pathogenesis of such abnormalities is not completely explained. The hypothesis of an imbalance in vasoactive mediators and angiogenic factors has been put forward. Increasing data support the theory that the increase in synthesis and release of nitric oxide (NO) is the key factor modulating vascular tone. If this hypothesis is true, the use of compettive inhibitors of NO synthesis should restore pulmonary vascular tone, reversing the hemodynamic changes and gas exchange impairment of HPS.

Animals↗

[Association of sarcoidosis and hemorrhagic rectocolitis in an insulin-dependent diabetic].

Ulcerative colitis and sarcoidosis are seldom associated. A 33-year-old diabetic man developed simultaneously a rectitis and a non-productive cough leading to the diagnosis of ulcerative colitis and sarcoidosis. These diagnoses are discussed because of the possible gastrointestinal lesions from sarcoidosis or the respiratory disorders due to ulcerative colitis. Some pathophysiological evidence can be found in this case in favor of a non-fortuitous association.

Adult↗

Diversity of malaria in rice growing areas of the Afrotropical region.

It is well known that 'in many instances the rice agrosystem perfectly fits the ecological requirements of pathogens or vectors' and in fact 'malaria, schistosomiasis and Japanese encephalitis are important vector-borne diseases associated with rice production in developing countries' (IRRI, 1987). In spite of these fears, rice cultivation has been on the increase in the African region in response to demographic and economic pressures. However, although rice fields provide suitable breeding places for Anopheles mosquitoes and rice cultivation leads to an increase in the biting rates, the species which are adapted to these sites are not the same in all parts of Africa. Several examples illustrate this phenomenon: An. funestus in the rice fields of Madagascar, An. pharoensis in saline water rice fields in the delta of the Senegal river, An. arabiensis in northern Cameroon and Burundi, An. gambiae Mopti form in the Kou Valley (Burkina Faso) and An. gambiae Savanna form in the rice fields of Kafine near Bouaké (Côte d'Ivoire). The vectorial capacities of these species are not the same and malaria inoculation rates are not necessarily increased in the riceland agroecosystem. The consequences for malaria of introducing rice cultivation depend on the situation before its introduction: it could be worsened in unstable malaria areas but not in stable malaria areas. Therefore, sound epidemiological and entomological knowledge are needed before causing any environmental modifications for agricultural purposes and there should be regular monitoring to avoid any outbreak.

Burkina Faso↗