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Biomedical subjects

S Ledoux

Publications and source records attributed to S Ledoux.

At least 19 recordsLinked to original sources
PubMed2005

Expression of adiponectin and its receptors in swine.

Adiponectin is an adipocyte-derived hormone that plays an important role in lipid metabolism and glucose homeostasis. Objectives of this study were 1) to determine the presence and distribution of adiponectin and its receptors 1 and 2 (adipoR1 and adipoR2) in porcine tissues; 2) to characterize pig adiponectin, adipoR1, and adipoR2 mRNA levels in various fat depots from three different breeds of pigs; and 3) to study, in stromal-vascular cell culture, the effects of leptin and tumor necrosis factor-alpha (TNFalpha) on pig adiponectin, adipoR1, and adipoR2 gene expression. To this end, fat Chinese Upton Meishan (UM, n = 10), lean Ham Line (HL, n = 10), and Large White (LW, n = 10) gilts were used. We report the isolation of partial cDNA sequences of pig adipoR1 and adipoR2. Porcine-deduced AA sequences share 97 to 100% homology with human and murine sequences. Pig adipoR1 mRNA is abundant in skeletal muscle, visceral fat, and s.c. fat tissues, whereas adipoR2 mRNA is predominantly expressed in liver, heart, skeletal muscle, and visceral and s.c. fat tissues. Pig adiponectin mRNA levels in s.c. and visceral fat tissues were not associated with plasma insulin and glucose in fasting animals. Subcutaneous (r = -0.44, P < 0.05), visceral (r = -0.43, P < 0.05), and total body fat (r = -0.42, P < 0.05) weights were negatively correlated with adiponectin mRNA levels measured in visceral, but not s.c., fat. Pig adipoR1 and adipoR2 mRNA levels, in visceral fat, were less expressed in fat UM gilts than in the lean HL gilts (P < 0.05). Inverse associations were found between s.c. (r = -0.57, P < 0.01), visceral (r = -0.46, P < 0.05), and total body fat (r = -0.56, P < 0.01) weights and adipoR2 mRNA levels in visceral fat only. We were unable to find such associations for adipoR1 mRNA levels in the overall gilt population. The current study demonstrated that TNFalpha downregulates adiponectin and adipoR2, but not adi-poR1, mRNA levels in stromal-vascular cell culture. Moreover, leptin significantly decreased adiponectin mRNA levels, whereas there was no effect on adiponectin receptors. We conclude that adiponectin and adi-poR2 mRNA levels, but not adipoR1, are modulated in pig visceral fat tissues. Furthermore, our results indicate that TNFalpha interferes with adiponectin function by downregulation of adipoR2 but not of adipoR1 mRNA levels in pigs.

Adiponectin↗
PubMed2003

Hypoxia enhances Ecto-5'-Nucleotidase activity and cell surface expression in endothelial cells: role of membrane lipids.

Extracellular adenosine production by the glycosyl-phosphatidyl-inositol-anchored Ecto-5'-Nucleotidase plays an important role in the defense against hypoxia, particularly in the intravascular space. The present study was designed in order to elucidate the mechanisms underlying hypoxia-induced stimulation of Ecto-5'-Nucleotidase in endothelial cells. For this purpose, aortic endothelial cells (SVARECs) were submitted to hypoxic gas mixture. Hypoxia (0% O2 for 18 hours) induced a 2-fold increase of Ecto-5'-Nucleotidase activity (Vmax 19.78+/-0.53 versus 8.82+/-1.12 nmol/mg protein per min), whereas mRNA abundance and total amount of the protein were unmodified. By contrast, hypoxia enhanced cell surface expression of Ecto-5'-Nucleotidase, as evidenced both by biotinylation and immunostaining. This effect was accompanied by a decrease of Ecto-5'-Nucleotidase endocytosis, without modification of Ecto-5'-Nucleotidase association with detergent-resistant membranes. Finally, whereas cholesterol content was unmodified, hypoxia induced a time-dependent increase of saturated fatty acids in SVARECs, which was reversed by reoxygenation, in parallel to Ecto-5'-Nucleotidase stimulation. Incubation of normoxic cells with palmitic acid enhanced Ecto-5'-Nucleotidase activity and cell surface expression. In conclusion, hypoxia enhances cell surface expression of Ecto-5'-Nucleotidase in endothelial cells. This effect could be supported by a decrease of Ecto-5'-Nucleotidase endocytosis through modification of plasma membrane fatty acid composition.

5'-Nucleotidase↗
PubMed2002

Lovastatin enhances ecto-5'-nucleotidase activity and cell surface expression in endothelial cells: implication of rho-family GTPases.

Extracellular adenosine production by the GPI-anchored Ecto-5'-Nucleotidase (Ecto-5'-Nu) plays an important role in the cardiovascular system, notably in defense against hypoxia. It has been previously suggested that HMG-CoA reductase inhibitors (HRIs) could potentiate the hypoxic stimulation of Ecto-5'Nu in myocardial ischemia. In order to elucidate the mechanism of Ecto-5'-Nu stimulation by HRIs, Ecto-5'-Nu activity and expression were determined in an aortic endothelial cell line (SVAREC) incubated with lovastatin. Lovastatin enhanced Ecto-5'-Nu activity in a dose-dependent manner. This increase was not supported by de novo synthesis of the enzyme because neither the mRNA content nor the total amount of the protein were modified by lovastatin. By contrast, lovastatin enhanced cell surface expression of Ecto-5'-Nu and decreased endocytosis of Ecto-5'-Nu, as evidenced by immunostaining. This effect appeared unrelated to modifications of cholesterol content or Ecto-5'-Nu association with detergent-resistant membranes. The effect of lovastatin was reversed by mevalonate, the substrate of HMG-CoA reductase, by its isoprenoid derivative, geranyl-geranyl pyrophosphate, and by cytotoxic necrotizing factor, an activator of Rho-GTPases. Stimulation of Ecto-5'-Nu by lovastatin enhanced the inhibition of platelet aggregation induced by endothelial cells. In conclusion, lovastatin enhances Ecto-5'-Nu activity and membrane expression in endothelial cells. This effect seems independent of lowering cholesterol content but could be supported by an inhibition of Ecto-5'-Nu endocytosis through a decrease of Rho-GTPases isoprenylation.

5'-Nucleotidase↗
PubMed2001

Phenomenology, psychosocial correlates, and treatment seeking in major depression and dysthymia of adolescence.

OBJECTIVE: To compare phenomenology, psychosocial correlates, and treatment seeking in DSM-Itt-R major depression and dysthymia among adolescents diagnosed as cases in a community-based study. METHOD: A self-report questionnaire, including psychosocial data, life events, eating behaviors, depressive symptoms, substance use, pathological behaviors, and family and school functioning was administered to a nonselected sample (N = 3,287, 93.2% of targeted population) of adolescents aged 11 to 20 years from several Haute-Marne communities in France in 1988-1989. Subgroups of subjects (n = 205, 84.7% of eligible subjects) were interviewed with a structured diagnostic schedule, and adolescents with major depression (n = 49), dysthymia (n = 21) and controls (n = 135) were compared. RESULTS: Nearly 30% of controls had at least one current symptom of depression. Patterns of affective symptoms were similar in major depression and dysthymia, but significant differences emerged in comorbid conditions (more anxiety disorders, suicidal behaviors, and alcohol intoxications associated with major depression) and stressor at onset (more severe in major depression). Experiences of loss during the prior 12 months were associated with both forms of affective disorder, while poor family relationships were specific correlates of dysthymia. In contrast, peer relationships and pathological behaviors did not differ between depressed subjects and controls. Although psychosocial functioning was significantly impaired in both groups of depressed adolescents, treatment seeking was limited to 34.7% for major depressive subjects and 23.8% for dysthymic subjects. CONCLUSION: The results provide evidence that major depression and dysthymia in adolescence are equally severe but may have distinct patterns in associated factors. Despite free access to health care, the rate of treatment seeking for mood disorders in France is similar to that reported in U.S. studies.

Adolescent↗
PubMed2001

Impairment of coronary microvascular dilation in response to cold pressor--induced sympathetic stimulation in type 2 diabetic patients with abnormal stress thallium imaging.

Coronary microcirculation dysfunction may be associated with myocardial perfusion defects on thallium imaging in diabetic patients without coronary artery stenosis. Microvascular coronary adaptation to increased myocardial oxygen demand in response to sympathetic stimulation evoked by the cold pressor test was examined in 22 type 2 diabetic patients with thallium imaging defects and in 15 control subjects. Both the diabetic patients and control subjects had angiographically normal coronary arteries and no other risk factors. Despite a similar increase in the rate-pressure product in the two groups (22.6 +/- 12.4% in diabetic patients and 31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in the left anterior descending artery (mean flow velocity measured by intracoronary Doppler multiplied by the cross-sectional area measured by digital angiography) was significantly lower in diabetic patients than in control subjects (14.7 +/- 19.8 vs. 75.5 +/- 13.5%, respectively; P = 0.0001). In addition, when there was a positive correlation between the two parameters in control subjects (r = 0.651, P < 0.01), there was no relationship in diabetic patients (r = 0.054). In conclusion, vasodilation of the coronary microcirculation in response to sympathetic stimulation evoked by the cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilation during current life stress episodes such as exercise, mental stress, or cold exposition.

Blood Flow Velocity↗
PubMed2001

[Is aggressiveness really inhibited in asthmatic adolescents? An epidemiological approach].

Clinical data support the hypothesis that aggressivity is inhibited amongst asthmatics. The relationship of violence, as a marker of aggressiveness, to asthma was examined in a population-based sample of 12.466 students of secondary schools in France (Enquête sur la Santé de l'adolescent 1993/1994) using an epidemiological questionnaire on health status, life events, potential risk factors and disease management. Twelve percent of the students reported having had at least one episode of asthma, 4% had asthma attacks, and 1% had severe asthma at the time of the survey. Asthma had been confirmed by a physician in 81% of the cases. Acts of violence [fits of violence (21%), screaming when angry (30%), hitting when angry (45%), 'racketeering' (1%)] or sustained violence [physical aggressions (15%) and rape (4%)] were significantly related to asthma in past year when applying a logistic model including age, sex, ethnic group, socioeconomical status, geographical zone, and type of school as potential confounders (adjusted odds-ratios ranging from 1.26 to 1.87 and from 1.44 to 3.48 respectively). Similarly, violence was related to severe asthma. Results persisted after exclusion of individuals for whom asthma had not been confirmed by a physician. These findings strongly challenge the current hypothesis according to which aggressiveness is inhibited in asthmatic adolescents.

Adolescent↗
PubMed2001

[Inhibition of iron-catalyzed oxidative reactions restores mathcing between coronary blood flow and myocardial metabolic demand in type 2 diabetes].

In diabetes, endothelium-dependent dilation of large and small coronary arteries is impaired, which results in a mismatch between myocardial metabolic demand and coronary blood flow. It has been proved that deferoxamine, an iron chelator that inhibits Fenton and Haber-Weiss reactions, restores a normal response to cold pressor test and flow increase in angiographically normal epicardial coronary arteries of diabetic patients. This result suggests that nitric oxide could be inactivated by reactive oxygen species. The aim of this study was to assess the effects of deferoxamine on coronary microcirculation vasomotion when myocardial oxygen demand is increased by sympathetic stimulation elicited by cold pressor test in type 2 diabetic patients. In 17 patients with angiographically normal coronary arteries and without any other coronary risk factors, coronary blood flow has been measured using quantitative angiography and intracoronary Doppler at baseline and during a cold pressor test, before and after intravenous administration of 500 mg deferoxamine. Increase in rate-pressure product, an estimate of myocardial metabolic demand, was similar before and after deferoxamine (+21.1 +/- 8.7% vs +20.5 +/- 8.9%, respectively), but coronary blood flow increase was significantly higher after deferoxamine (+6.3 +/- 12.9% vs +31.8 +/- 16.7%, respectively, p < 0.001), and coronary resistance was increased before deferoxamine and decreased after (+14.8 +/- 21.9% vs -7.9 +/- 10.9%, respectively, p < 0.001). Moreover, before deferoxamine, the negative correlation between coronary blood flow and rate-pressure product changes before deferoxamine (R = 0.518, P < 0.05) was turned in a positive relationship after deferoxamine (r = 0.546, p < 0.05). In conclusion, in type 2 diabetic patients, endothelium-dependent dilation of the coronary microcirculation is restored when iron-catalysed oxidative reactions are inhibited by deferoxamine, which restores the normal matching between myocardial oxygen demand and coronary blood flow.

Adult↗
PubMed2001

[Insulin and weight gain: myth or reality?].

Most patients with type 2 diabetes gain weight when treated with insulin. Weight gain is observed when insulin is introduced after oral agents have failed, but also when insulin is introduced shortly after the diagnosis of diabetes. The mechanisms of this weight gain are incompletely understood, but reduction of energy lost by glucosuria and reduction of energy needed for glucose production are main determinants. The same reasons apply to the weight gain observed at the beginning of treatment with sulfonylureas, even though patients usually gain less weight with sulfonyulreas than with insulin. In the UKPDS, at 10 years of the study, patients treated with insulin gained 2 kg more, i.e. 2.5% of the average weight of patients included in the trial, than patients treated with sulfonylureas. The reasons of the excess of weight gain with insulin as compared with sulfonylureas remain unclear. Patients with type 2 diabetes treated with insulin gain weight only during the first 2-3 years after insulin introduction. The weight stabilizes thereafter. Type 2 diabetes usually remains unknown for years before diagnosis and patients may lose weight during this long period of time preceding diagnosis. It is hypothesized that the weight gain observed after the introduction of insulin may simply correspond to the reexpression of the physiologically controlled body weight.

Diabetes Mellitus, Type 2↗
PubMed2000

Early psychopathological signs in bulimia nervosa. A retrospective comparison of the period of puberty in bulimic and control girls.

While bulimia nervosa (BN) typically begins in girls during late adolescence, puberty and associated developmental changes have been linked to negative body image and onset of a variety of psychological problems. This study aimed to identify early psychopathological signs, which could have marked the period of puberty in subjects whom later developed BN. In a case control study, we compared 49 girls with BN according to DSM-IV, aged between 18 and 20 years, to 49 girls of the same age, who were free of any past or current psychiatric diagnosis. Psychiatrists or clinical psychologists, using a semi-structured clinical interview including retrospective assessment of the emotional and behavioural changes that had occurred in puberty evaluated both groups. Before the onset of a clinical eating disorder, the subjects with BN presented significantly more often than controls weight related concerns, attitudes of withdrawal and social isolation, and negative changes in their body image and self-image, as well as in their relationships with siblings and peers. The results suggest that early psychological distress precedes the onset of an eating disorder in many cases, and that prevention efforts should be directed towards peripubertal psychopathology.

Adolescent↗
PubMed2000

Prevalence and severity of asthma in adolescents in France. Cross-sectional and retrospective analyses of a large population-based sample.

SETTING: Asthma is the most common chronic respiratory disease among adolescents; however, very little is known about asthma in this age group. OBJECTIVE: To explore asthma in adolescence using cross-sectional and retrospective representative data. DESIGN: A population-based sample of adolescents was selected from 578 classes in 186 schools of eight metropolitan educational districts in France and invited to complete a self-administered questionnaire (National Adolescent Health Survey [NAHS]). RESULTS: Of 14,278 adolescents selected, 12,466 (87%) participated in the survey. Prevalence of 'ever asthma' was higher among boys, among those in the south and west, among those from French overseas departments, in active smokers, and in those with other allergies, including food allergy. It was lower in adolescents whose mother was a housewife. Puberty was not associated with 'ever asthma'; however, asthmatic boys without signs of puberty usually had more attacks than those with. Severe asthma was associated with early onset and female sex. Asthma medications and consultations did not depend on socio-economic status. Asthmatic adolescents were found to need more health care in terms of medication use, consultations and hospitalisations other than for asthma than other adolescents; this relationship was strongest among severe asthmatics.

Adolescent↗
PubMed2000

[Dysfunction of the coronary microcirculation in type 2 diabetic patients].

A failure of coronary blood flow to increase during cold pressor test has been shown in patients with coronary atherosclerosis and impaired metabolic coronary vasodilatation in response to atrial pacing has been demonstrated in diabetic patients without significant epicardial artery stenoses. This study was designed to evaluate coronary microvascular adaptation to increased myocardial oxygen demand in response to sympathetic stimulation in diabetic patients with angiographically normal coronary arteries. Microvascular coronary adaptation to increased myocardial oxygen demand due to sympathetic stimulation evoked by the cold pressor test has been examined in 22 type 2 diabetic patients and in 15 control subjects with angiographically normal coronary arteries and no other risk factors. Coronary blood flow was calculated by measuring mean flow velocity in left anterior descending coronary artery by intracoronary Doppler and cross sectional area of the artery by digital angiography. Results show that despite a similar increase in rate-pressure product in the 2 groups (+22.6 +/- 12.4% in diabetic patients and +31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in left anterior descending artery was significantly lower in diabetic patients than in control subjects (+14.7 +/- 19.8% vs +75.5 +/- 13.5%, respectively, p = 0.0001). In addition, when there was a positive correlation between the 2 parameters in control subjects (R = 0.651, p < 0.01), there was no relationship in diabetic patients (R = 0.054). In conclusion, this study demonstrates that vasodilatation of coronary microcirculation in response to sympathetic stimulation evoked by cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilatation during current life stress episodes such as exercise, mental stress or cold exposure.

Adaptation, Physiological↗
PubMed1999

Consultation of mental health professionals by French adolescents with probable psychiatric problems.

A national sample of school-attending adolescents aged 12-20 years (n = 8435) filled out an anonymous self-administered questionnaire. We considered a group of 868 adolescents with probable psychiatric problems (PPP) in order to identify personal, psychological and environmental factors as well as help-seeking behaviour associated with consultation of mental health professionals (MHP). Among the adolescents with PPP, 13.7% consulted MHP at least once during the year. Logistic regression analysis showed that consultation with MHP was more frequent for adolescents with multiple problems (OR = 2.3), functional physical disorders (OR = 1.9), family problems (OR = 2), separated parents (OR = 4.4) or multiple contacts with other doctors (GP, school doctor and other specialists, OR = 2.2, 3.6 and 2.6, respectively), and among those who confided in teachers or youth group advisors (OR = 2.2). Those who confided in peers consulted MHP less often (OR = 0.5). However, consultation with MHP was not associated with other sociodemographic or educational characteristics, with type of problem (internalized or externalized), or with confiding in one's parents.

Adolescent↗
PubMed1998

Expression of ced-3 and ced-9 homologs in Alzheimer's disease cerebral cortex.

In order to characterize cell death mechanisms involved in Alzheimer disease (AD), we quantitated the expression of ced-3 and ced-9 homologs in AD frontal cortex. Positive (ICE, ICErel-II, ICErel-III, Ich-1L, CPP32, mch2, mch3, bcl-xS, bax and bak) and negative (bcl-2, bcl-xL, MCL1 and Ich-1S) regulators of apoptosis were successively examined using a semi-quantitative technique of reverse transcription-polymerase chain reaction (RT-PCR). Total RNA was extracted from postmortem frontal cortex of AD patients (n = 7) and controls (n = 7) matched for age and autolysis time. Baseline levels of message were detected for 3 ced-3 (CPP32, Ich-1 and ICE) and 4 ced-9 homologs (bcl-x, MCL1, bcl-2 and bax) in the frontal cortex. There was an overexpression of the ICEalpha cDNA in AD patients as compared with age-matched controls (P = 0.03). Our results indicate that several ced-3 and ced-9 homologs are expressed in the adult human brain, and suggest that neuronal cell death in AD might involve an aberrant expression of ICEalpha.

Adult↗
PubMed1998

Coronary artery responses to physiological stimuli are improved by deferoxamine but not by L-arginine in non-insulin-dependent diabetic patients with angiographically normal coronary arteries and no other risk factors.

BACKGROUND: Acetylcholine produces coronary artery (CA) constriction in diabetic patients, suggesting an impairment of endothelium-dependent dilation. In diabetes, multiple metabolic abnormalities may inactivate nitric oxide through oxygen free radical production. METHODS AND RESULTS: To examine the mechanism of this abnormal response, two physiological tests (ie, a cold pressor test [CPT] and coronary flow increase induced by an injection of 10 mg papaverine [PAP] in the distal left anterior descending CA) were performed before and after either intravenous L-arginine (625 mg/min x 10 minutes) or intravenous deferoxamine (50 mg/min x 10 minutes) in 22 normotensive nonsmoking diabetic patients with angiographically normal CAs and normal cholesterol. Coronary surface areas were measured with quantitative angiography. Before the administration of L-arginine or deferoxamine, CPT induced CA constriction in both groups (-14 +/- 10% and -15 +/- 11%, respectively; each P<.001), and PAP injection in distal LAD did not modify significantly proximal LAD dimensions. In the 10 diabetic patients receiving L-arginine, responses to CPT and PAP were not modified. Conversely, in the 12 patients receiving deferoxamine, CA dilated in response to the two tests (+10 +/- 9% after CPT and +22 +/- 7% after PAP, each P<.001). Intracoronary isosorbide dinitrate, an endothelium-independent dilator, produced similar dilation in the two groups (+47 +/- 19% and +41 +/- 15%, respectively; each P<.001). CONCLUSIONS: This study shows that (1) responses of angiographically normal CAs to CPT and to flow increase are impaired in diabetic patients; (2) abnormal responses are not improved by L-arginine, suggesting that a deficit in substrate for nitric oxide synthesis is not involved; and (3) deferoxamine restores a vasodilator response to the two tests, suggesting that inactivation of NO by oxygen species might be partly responsible for the impairment of CA dilation in diabetic patients.

Adult↗
PubMed1998

Gender differences in symptoms of adolescents reporting sexual assault.

Sexual assault on children and adolescents has become a common topic of study, but there has been little research into the specific characteristics of the population of male victims. A national survey representative of school-age adolescents in France enabled us to study 465 adolescents reporting sexual assault (121 boys, 344 girls; mean age 15.4, SD 2.5 years). Girls were shown to be more frequently affected by certain medicopsychological symptoms: nightmares, multiple somatic complaints and some items concerning mood disorders. On the other hand, behavioural symptoms were much more frequently expressed in boys, in particular: repeated suicide attempts, running away, fits of violence and substance use. Boys presenting these symptoms should be questioned as a matter of routine concerning a history of sexual assault.

Adolescent↗