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Biomedical subjects

T Coste

Publications and source records attributed to T Coste.

At least 37 records · Page 2Linked to original sources
PubMed1997

Alteration of Na,K-ATPase isoenzymes in diabetic cardiomyopathy: effect of dietary supplementation with fish oil (n-3 fatty acids) in rats.

Diabetic cardiomyopathy has been associated with a decrease in Na,K-ATPase activity and expression, as well as alterations in membrane lipid composition. The aim of this study was twofold: 1) to document in rats the effect of streptozotocin-induced diabetes on myocardial Na,K-ATPase and fatty acids, and 2) to evaluate the potential effect of a dietary supplementation with fish oil (n-3 fatty acids) on the streptozotocin-induced changes. Assays were performed in purified cardiac plasma membranes to determine Na,K-ATPase activity, expression of the different alpha- and beta-subunits of Na,K-ATPase, and the fatty acid content of total phospholipids. Relative abundance of the mRNAs encoding the alpha 1, alpha 2 and beta 1 isoforms was studied by Northern blot analysis. Results demonstrated that diabetes significantly decreased activities of alpha 1 and alpha 2 isoforms and mRNA levels of alpha 2 and beta 1 isoforms, and, at the protein level, increased alpha 1-isoforms and decreased both alpha 2- and beta 1-isoforms. Changes in fatty acid content of the membrane were consistent with inhibition of desaturase. Fish-oil supplementation produced an increase in membrane incorporation of eicosapentaenoic acid. It also increased the level of beta 1-isoforms and restored the activity of the alpha 2-isoenzyme without significant changes in the level of alpha 1- and alpha 2-isoforms. Northern blot analysis showed no effect of fish oil supplementation. Experimental diabetes and prevention by the fish oil rich (n-3 fatty acids) diet induced specific effects on the activity and expression of alpha and beta Na,K-ATPase subunit isoforms. These studies suggest that fish oil therapy may be effective in preventing some of the adverse consequences of diabetes.

Analysis of Variance↗
PubMed1997

Association of diabetic neuropathy with Na/K ATPase gene polymorphism.

Diabetes mellitus induces a decrease in Na/K ATPase activity in man and animals, and this decrease plays a role in the development of diabetic neuropathy. Na/K ATPase is encoded by various genes, of which the ATP1 A1 gene is expressed predominantly in peripheral nerves and in erythrocytes. To investigate whether a polymorphism in the Na/K ATPase genes could explain the predisposition of some patients with insulin-dependent diabetes mellitus (IDDM) to develop polyneuropathy, a restriction fragment length polymorphism (RFLP) of the ATP1 A1 gene was studied together with erythrocyte Na/K ATPase activity in 81 Caucasian patients with more than 10 years' duration of IDDM. Associations with diabetic neuropathy, retinopathy and nephropathy were sought. Digestion of the first intron of the ATP1 A1 gene by the Bgl II restriction enzyme revealed a dimorphic allelism. Frequency of the restricted allele was 0.18 in this selected series (however, it was 0.10 in representative samples of IDDM patients and of normal subjects in our area). Mean erythrocyte Na/K ATPase activity was lower in diabetic patients than in 42 control subjects (292 +/- 10, vs 402 +/- 13 nmol Pi.mg protein-1.h-1, p < 0.0001) and was not related to HbA1c value or to diabetes duration. It was lower in the group of the 28 patients bearing the restricted allele (241 +/- 10 vs 319 +/- 11 nmol Pi.mg protein-1.h-1, p < 0.0001). Neuropathy was absent in 50 patients, mild in 15 and severe in 16. When classified accordingly the three groups of patients did not differ with respect to sex, age and duration of diabetes. The respective frequency of the restricted allele among the groups was 10, 73 and 81%, (p < 0.0001) and mean erythrocyte Na/K ATPase activity was respectively: 322 +/- 10.7 nmol Pi.mg protein-1.h-1, 268 +/- 15 and 229 +/- 17, (p < 0.001). A borderline association between renal status or retinal status and repartition of polymorphism and a borderline correlation between renal status and Na/K ATPase activity were found, but significance disappeared after checking for the presence or absence of neuropathy. IDDM patients bearing the ATP1 A1 variant detected by Bgl II RFLP are much more frequently affected by neuropathy (relative risk 6.5, with 95% CI 3.3-13). Identification of this risk factor may help to prevent this complication. It is suggested that the restricted allele is in linkage disequilibrium with a genomic mutation allowing diabetes to induce a greater impairment of Na/K ATPase activity which could in turn favour the development of neuropathy.

Adult↗
PubMed1997

Multivariate analysis of pathophysiological factors in reflux oesophagitis.

BACKGROUND: Reflux oesophagitis is considered a multifactorial disease, but the respective roles of the main factors involved in its pathophysiology have not been clearly established. AIMS: To attempt to assign these roles by means of a multivariate logistic regression analysis of the main parameters associated with reflux oesophagitis. PATIENTS: Eighty seven patients with gastro-oesophageal reflux disease were studied: 41 without oesophagitis and 46 with reflux oesophagitis grade 1 to 3. METHODS: (1) Monovariate comparison of patients' characteristics and of parameters derived from in hospital 24 hour oesophageal pH monitoring, oesophageal manometry, double isotope gastric emptying studies, and basal and pentagastrin stimulated gastric acid and pepsin output determinations, between patients with and without oesophagitis. (2) Multivariate logistic regression analysis including the parameters significant in the monovariate analysis. RESULTS: Among the 16 significant parameters from monovariate analysis, three significant independent parameters were identified by multivariate logistic regression analysis: number of refluxes lasting more than five minutes, reflecting oesophageal acid clearance (p = 0.002); basal lower oesophageal sphincter pressure (p = 0.008); and peak acid output (p = 0.012). These three parameters were not correlated with each other. The multivariate model was highly discriminant (correct classification of 81.3% of the cases (95% confidence intervals 0.723, 0.903). Risk for oesophagitis increased as a function of the tercile threshold values of the three parameters. Odds ratios of the three parameters for oesophagitis risk were similar, regardless of whether they were calculated when the patients were compared as a function of oesophagitis grade or the presence or absence of oesophagitis. CONCLUSIONS: This multivariate approach adds evidence that impaired oesophageal acid clearance and hypotonic lower oesophageal sphincter are the two major independent pathophysiological factors of oesophagitis, but also showed that the acid secretion level is an independent pathophysiological factor.

Adult↗
PubMed1996

Role of salivary and seric epidermal growth factor in pathogenesis of reflux esophagitis in chronic alcoholics and nondrinkers.

Our objective was to investigate the putative role of epidermal growth factor (EGF) in esophagitis pathogenesis in both nondrinkers and chronic alcoholics. We studied the EGF serum level, the EGF salivary concentration, and the esophageal EGF receptor expression in different groups of patients with esophagitis: nondrinkers with typical symptoms of gastroesophageal reflux (N = 12) and chronic alcoholics (N = 12), and in controls: chronic alcoholics without esophagitis (N = 16) and healthy nondrinkers (N = 12). All patients had an endoscopy with esophageal biopsies, 24-hr esophageal pH-metry, and esophageal manometry. EGF serum levels and EGF salivary concentrations were determined by radioimmunoassay. EGF receptor expression was determined by immunohistochemistry. Both the EGF serum level and the EGF salivary concentration remained constant, 328 +/- 21 pg/ml and 305 +/- 48 pg/ml, respectively, regardless of alcohol intake and the presence or absence of esophagitis. In addition, the presence of esophagitis did not affect the EGF receptor expression. These results suggest that seric and salivary EGF is not involved in the pathogenesis of reflux esophagitis in nondrinkers and in chronic alcoholics.

Adult↗
PubMed1996

Decreased Na/K ATPase ouabain binding sites in red blood cells of patients with insulin-dependent diabetes and healthy north African control subjects: relationship with diabetic neuropathy.

Like other degenerative complications occurring during diabetes, development of neuropathy is determined mainly by the duration of disease and quality of control. However, there may be some predisposing factors. Activity of Na/K ATPase has been implicated in the pathophysiology of diabetic neuropathy. A decrease in the activity of this enzyme has been observed in red blood cells of poorly controlled diabetic patients and healthy North African subjects who are predisposed to diabetic neuropathy. This study was performed to characterize abnormalities of Na/K ATPase activity in these two populations. For this purpose we measured enzyme activity (hydrolysis of ATP) and the number of enzyme units (number of binding sites for ouabain) in the red blood cells of three groups of men, i.e., healthy Caucasian subjects, healthy North African subjects and Caucasian insulin-dependent diabetic patients. The level of Na/K ATPase activity and the number of enzyme units were about 30% lower in the red blood cells of diabetic patients and North African subjects, than in healthy Caucasian controls. In healthy North African subjects predisposed to neuropathy in case of development of diabetes, the decrease in enzymatic activity was correlated with a decrease in the number of enzyme units. This correlation was not observed in diabetic patients. We speculate that the constitutional decrease in Na/K ATPase activity in healthy North African subjects corresponds to a quantitative defect, whereas the acquired decrease in diabetic patients corresponds to a qualitative defect probably related to the structure of the lipid membrane.

Adult↗
PubMed1996

[Treatment with octreotide of stenosing cystic dystrophy on heterotopic pancreas of the duodenal wall].

Cystic dystrophy of the duodenal wall developing in heterotopic pancreas is a rare disease. Weight loss and painless vomiting due to duodenal stenosis where the main clinical manifestations of this entity in a chronic alcoholic patient. Diagnosis was made by using an ultrasonic-endoscope equipped with a miniprobe. Although surgical treatment is usually recommended in this situation, the clinical condition of this patient improved dramatically after subcutaneous injections of somatostatin analog (octreotide). This treatment was maintained during 9 months and no recurrence was observed during the follow-up period.

Adult↗
PubMed1996

[Mesenteric panniculitis simulating Crohn disease].

Mesenteric panniculitis is a rare disease involving the adipose tissue of the mesentery. We report a case of a 27-year-old woman with mesenteric panniculitis, who presented clinical and radiological features mimicking Crohn's disease. In the outcome, she presented a small bowel perforation, unusual in this pathology, and an annexial involvement. This case reminds us of the role of sepsis and repeated abdominal surgery in relation to the pathogenesis of mesenteric panniculitis. We report the first case of mesenteric panniculitis mimicking Crohn's disease.

Adult↗
PubMed1995

Absence of human papillomavirus DNA detected by polymerase chain reaction in French patients with esophageal carcinoma.

BACKGROUND & AIMS: Recent studies have suggested that esophageal human papillomavirus infection could be a risk factor for esophageal squamous cell carcinoma. The aim of this study was to evaluate the prevalence of human papillomavirus DNA sequences in the esophagus of French patients with esophageal squamous cell carcinoma. METHODS: Multiplex polymerase chain reactions with consensus primers directed to the L1 gene or specific primers for human papillomavirus types 6, 11, 16, 18, 31, and 33 directed to E6 gene (40 cycles followed by restriction mapping of the amplified products) were used to determine the presence of human papillomavirus DNA sequences in esophageal squamous cell carcinoma (n = 75), normal adjacent mucosa (n = 49), and metastatic lymphadenopathies (n = 5). As an internal control, a target located in the embryonic myosin heavy-chain gene was used in each reaction. RESULTS: Human papillomavirus DNA sequences could not be detected in any of the tumoral samples, the normal adjacent mucosa, or the metastatic lymphadenopathies. CONCLUSIONS: Human papillomavirus seems not to be implicated in esophageal carcinogenesis, at least in French patients, because the viral genomes are not associated with esophageal squamous cell carcinomas.

Adult↗
PubMed1995

[Prevalence and risk factors of hepatitis C virus infection in a hospitalized population in a gastroenterology unit. Role of endoscopic biopsies].

OBJECTIVES AND METHODS: In order to study the prevalence and risk factors of HCV infection in a population hospitalized in a Gastroenterology Unit, 3,767 patients were tested for serum anti-HCV, and 2,607 filled out a questionnaire about risk factors. RESULTS: With the RIBA 2 test, the overall prevalence was 5.9%. Because of the age distribution, two populations were studied. In patients younger than 45, intravenous drug use was the only independent risk factor linked to serum anti-HCV positivity (Odds ratio: 151, CI 95%: 66.9-340). In patients older than 45, the independent risk factors were chronic liver disease (Odds ratio: 8.5, CI 95%: 4.4-16.8), per-endoscopic biopsies (Odds ratio: 2.7, CI 95%: 1.4-5.4), and blood transfusions (Odds ratio: 1.8, CI 95%: 0.9-3.5). Two variables were dominant for the entire population: IV drug use and chronic liver disease. In patients without these factors, only one risk factor was linked to serum anti-HCV positivity: perendoscopic biopsies (Odds ratio: 5.2, CI 95%: 1.6-16.5). CONCLUSION: These results suggest that HCV may be transmitted by perendoscopic biopsies.

Adult↗
PubMed1995

Quantitative analysis of transforming growth factor beta 1 messenger RNA in the liver of patients with chronic hepatitis C: absence of correlation between high levels and severity of disease.

Transforming growth factor beta 1 (TGF beta 1) is a cytokine involved in liver fibrogenesis. Previous semiquantitative studies of patients with chronic viral hepatitis showed that liver TGF beta 1 messenger RNA (mRNA) was increased, compared with normal controls and with patients with chronic hepatitis C virus (HCV) infection who responded favorably to interferon alfa (IFN alpha) treatment. To evaluate its potential prognostic significance, we measured liver TGF beta 1 mRNA, using a new competitive reverse gene amplification assay, in a total of 35 patients with chronic HCV. This technique was reproducible and sensitive; we could measure as few as 5,000 molecules of TGF beta 1 mRNA per microgram of total liver RNA. In patients with chronic HCV, the mean level of TGF beta 1 mRNA was 200-fold higher than in controls. However, no correlation could be found between TGF beta 1 mRNA and either the biological (serum amino-terminal peptide of type III procollagen) and histological (Knodell scores) indices of liver fibrosis or a favorable response to IFN alpha therapy. In 9 patients, second liver specimens were obtained after treatment; in most cases, TGF beta 1 mRNA levels and hepatic histological findings varied in parallel. These data are consistent with the hypothesis that TGF beta 1 plays a role in stimulating liver fibrogenesis during chronic HCV, despite the lack of prognostic value of TGF beta 1 mRNA levels measured before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Metabolism and time-course excretion of murideoxycholic acid, a 6 beta-hydroxylated bile acid, in humans.

The metabolism and time-courses of urinary and fecal excretions of murideoxycholic acid (MDCA; 3 alpha,6 beta-dihydroxy-5 beta-cholanoic acid), a 6 beta-hydroxylated bile acid, was investigated in man. The study was carried out in two groups of subjects. Six cholecystectomized patients fitted with a cystic duct drain ingested 100 mg of a tracer dose of 3H-MDCA. Time-course of radioactivity in plasma was then followed for an 8-h period. Biliary, urinary and fecal excretions of radioactivity were measured for a 5-day period and excreted MDCA metabolites were identified. Five lithiasic patients with intact enterohepatic circulation ingested 500 mg of the same tracer dose of 3H-MDCA. Radioactivity in plasma was followed for a 49-h period and urinary and fecal excretions of radioactivity were measured daily for 7 days. In the first group, the excretion of the radioactivity by the three routes (bile+urine+feces) reached 97.8 +/- 1.5% of the ingested dose but dropped to 75 +/- 8.3% (urine+feces) in patients in the second group. In cholecystectomized patients, the estimation of intestinal MDCA absorption was dependent on cystic duct drain flow rate and gave values ranging from 20% to 87%. The biological half-life of MDCA in lithiasic patients averaged 3.4 +/- 0.7 days. Radioactivity appeared in the plasma in the first hour and reached a maximum 6 and 3 h after the beginning of the experiment in group I and II respectively. In the second group, another peak of radioactivity in plasma was observed just after breakfast.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Reduction of postprandial lipemia after acute exposure to high altitude hypoxia.

The effects of acute exposure to high altitude hypoxia upon plasma levels of lipids and lipoproteins were studied in 6 healthy subjects observed under strict dietary control. Fasting and postprandial values, first measured at low altitude (< 300 m), were compared to values measured 7 days after transfer by helicopter to the Observatoire Vallot (4350 m) near Mont-Blanc. Plasma levels of catecholamines and thyroid hormones were measured in parallel. Under normoxic conditions, a rise in plasma levels of cholesterol, triglycerides and phospholipids was found 4 hr after the test-meal, whereas circulating norepinephrine fell. Under hypoxic conditions, postprandial effects on lipid parameters disappeared, lipemic responses to the test-meal were dramatically reduced and plasma levels of norepinephrine increased. These effects were accompanied by a fall in triglyceride-rich lipoproteins, generally associated with a slight elevation of HDL-cholesterol, especially the less dense HDL2 fraction. When all results obtained in normoxic and hypoxic conditions were analyzed together, a series of highly significant correlations were found between the magnitude of postprandial lipidemia and various lipid parameters, in particular HDL2-cholesterol which was negatively correlated. These observations strongly suggest that high altitude hypoxia, independent of interfering variables such as exercise training or cold exposure, induced a net stimulation of the lipolysis of plasma triglycerides.

Adult↗