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Biomedical subjects

M Dumas

Publications and source records attributed to M Dumas.

At least 19 recordsLinked to original sources

Twenty-four-hour profiles and sleep-related variations of cortisol, thyrotropin and plasma renin activity in healthy African melanoids.

The 24-h hormone profiles have been well documented in caucasians living in a temperate climate, but they have never been examined in melanoid subjects under equatorial conditions, with a 12-h light-dark cycle in a hot climate. To establish normal data for this population, blood samples were taken at 10-min intervals over 24 h in five healthy young melanoids living in Abidjan (Ivory Coast). Cortisol and thyroid stimulating hormone (TSH) concentrations and plasma renin activity (PRA) were determined by radio-immunoassay and sleep was registered using polysomnography. Data were compared with results obtained in Strasbourg (France) from six healthy aged-matched caucasians. The 24-h profile of cortisol concentration was similar in both groups, with a 2-h phase advance in the melanoids. Nocturnal fluctuations of PRA, strongly linked to the rapid eye movement-non rapid eye movement (REM-NREM) sleep cycles, occurred in both groups, with higher levels in the caucasians in the last 2 h of sleep along with greater amounts of NREM sleep. After an evening increase in TSH, the sleep onset-related decrease seen in the caucasians was not observed in the melanoids. In both groups, increasing concentrations of TSH and cortisol occurred with awakening, decreasing concentrations being observed during slow-wave sleep. As in the caucasians studied in the temperate climates, the melanoid subjects living at the equator showed the same temporal organization of hormone rhythms within the 24-h period and the same relationships between the pulses and specific sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Headache and cysticercosis in Ecuador, South America.

Intractable headaches have been described as the presenting complaint of many patients with T. solium neurocysticercosis. We conducted a house-to-house neuroepidemiological survey of 2,723 residents of an Andean community, known to be endemic for this infection. Migraine headaches were confirmed in 187 cases (68.7 per thousand), and tension headaches were diagnosed in 77 cases (28.3 per thousand). Fifty-seven migraine sufferers accepted computed tomography examination, and in 19 it revealed neurocysticercosis. In 11 out of 52 migraineurs who had their blood drawn, electron immunotransfer blot testing (EITB) was positive for anticysticercal antibodies. In a computer-generated random sample of this community, 109 headache-free individuals were examined by CT, and 87 had EITB. Of the 109 subjects examined by CT, 14 were positive for cysticercosis. Of the 87 individuals tested by EITB, 7 were positive. A statistically significant difference between the symptom-free general population and the migraine patients was obtained for both CT (odds ratio 3.39, P < 0.005) and EITB (odds ratio 3.07, P < 0.05) diagnosis of neurocysticercosis. Neurocysticercosis appears to be a significant risk factor for the presentation of migraine-type headaches in areas endemic for T. solium infection.

Adolescent

Prevalence of neurological disorders in Haute-Vienne department (Limousin region-France).

The Limousin region had at present one of the largest elderly populations in France and in Europe. To determine the frequency of certain neurological disorders in the elderly, a neuroepidemiological survey was conducted in 1986-1987 on a representative sample of the population in Haute-Vienne (the most population-dense department in the Limousin region). This study used a WHO protocol which was first introduced at the beginning of the 1980s. It had been previously tested in France on a pilot population in 1984. The prevalences of the principal neurological disorders encountered per 100,000 inhabitants were as follows: nonmigraine headache 5,059, migraine 4,270, epilepsy 788, completed stroke 1,445, transient ischemic attacks 657, neuropathy 1,642, Parkinson's disease 328, and dementia 197.

Adolescent

Twenty-four-hour plasma cortisol and prolactin in human African trypanosomiasis patients and healthy African controls.

We have previously demonstrated that human African trypanosomiasis (sleeping sickness) at the stage of meningoencephalitis results in a major disruption of the circadian rhythmicity of sleep and wakefulness that is proportional to the severity of the disease. This paper examines the corresponding 24-hourly secretion in cortisol and prolactin and compares it with the hourly distribution of sleep composition in infected patients and healthy African subjects. The secretion of cortisol in humans follows a circadian rhythm relatively independent of the sleep-wake cycle, whereas that of prolactin exhibits fluctuations over the 24-hr day that are strongly related to the sleep-wake cycle. After the clinical classification of the patients according to the severity of the disease, hourly blood samples were taken over 24 hr via an indwelling catheter. Plasma cortisol and prolactin were analyzed by radioimmunoassay, and the variations in the hourly concentrations were analyzed for the presence of a potential 24-hr rhythm (circadian). All of the healthy African subjects showed significant circadian rhythms in both cortisol and prolactin secretion, similar to data on humans from temperate regions, and a sleep-related anamnestic afternoon peak of prolactin. Major disruptions in the circadian rhythms of plasma cortisol and prolactin were found in the three patients with the most severe illness, in contrast to the four who were less severely ill and the healthy controls. Thus, it appears that as the disease progresses in severity, major disruptions begin to occur in body circadian rhythms, not only in the sleep-wake cycle as reported elsewhere, but also in cortisol and prolactin secretion, suggesting that sleeping sickness affects the circadian timing system.

Adolescent

[Comparative activity of asiaticoside and madecassoside on type I and III collagen synthesis by cultured human fibroblasts].

Type I and III collagens are the major components of skin dermis. Skin aging is related mainly to a decrease in type I collagen levels. Collagen I also plays an important role in wound healing. An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of secretion of type I and III collagen in human fibroblast cultures with or without asiaticoside and madecassoside. Normal adult dermal fibroblast cultures were established using the explant method from a skin (lifting) sample obtained from a 50 year-old woman. Fibroblasts were grown to confluence in supplemented E 199 medium and after 24 hours of growth, products were added in serum free medium containing 0.15 mM sodium ascorbate. The media were then collected and type I and III collagen secretion levels determined. Kinetics of type I and III collagen secretion led to determine the effects to asiaticoside and madecassoside after 48 hours for collagen I secretion and 72 hours for collagen III. Two triterpenes with an ursenoic skeleton, asiaticoside and madecassoside, were shown to stimulate collagen secretion. Type I secreted collagen (for 10(4) fibroblasts per 48 hours) was increased for 25-30% with asiaticoside and madecassoside. Interestingly, only Madecassoside was able to increase significantly collagen III secretion.

Anti-Infective Agents

Flow cytometric analysis of human epidermal cell ageing using two fluorescent mitochondrial probes.

Cardiolipin, mitochondrial transmembrane potential, cell refringence and cell diameter were examined in epidermal cells obtained from 42 women between 9- to 75-year-old. The study was carried out in situ by flow cytometry on cells having incorporated either Nonyl Acridine Orange or Rhodamine 123, 2 mitochondria-specific dyes. Cardiolipin levels, determined by the binding of the cardiolipin-specific probe Nonyl Acridine Orange, decreased significantly with age, especially in young individuals. This suggests 2 stages in the age-dependent transformation of mitochondria (organelle number and/or size): one during childhood development and to adulthood (9 to 27 years) in which cardiolipin levels decrease dramatically (slope: -3.742; p = 0.0243) and the other corresponding to senescence (35 to 75 years) in which this decrease is less pronounced (slope: -0.618; p = 0.0467). These changes have no effect on mitochondrial potential, measured by Rhodamine 123 incorporation, which remained constant with age. This function, controlling calcium partitioning within the cell, might allow keratinocytes to differentiate and maintain the skin barrier function of the epidermis. Like cardiolipin, intrinsic parameters such as cell size and refringence also significantly decreased in epidermal cells from elderly subjects. The methodology can be used to determine physiological ageing in various cell types and to analyse human ageing and related parameters.

Acridine Orange

Human epidermal cells progressively lose their cardiolipins during ageing without change in mitochondrial transmembrane potential.

Mitochondria dysfunction is considered to be a major cause of the modifications that occur during cell ageing. For this reason, cardiolipin, a suitable marker of the chondriome, as well as the mitochondrial transmembrane potential were examined in keratinocytes obtained from 9- to 75-year-old women. The study was carried out by flow cytometry using two fluorescent mitochondria probes: nonyl acridine orange, which binds specifically to cardiolipin, and rhodamine 123, which is incorporated mainly in response to transmembrane potential. Cardiolipin levels in cells from elderly donors (75 years old) would be 57% lower (r = 0.540; P = 0.0002) than those in children (9 years old), while the inner transmembrane potential remained unchanged (r = 0.0394; P = 0.8017). The stability of the membrane potential may be explained by either or both of the following hypotheses: (i) the same pool of organelles able to maintain membrane potential is conserved even when cardiolipin levels decrease (ii) mitochondria membrane potential does indeed decrease with age but is compensated by glycolysis energy production. Finally, it may be stated that the fluorescent probes nonyl acridine orange and rhodamine 123 might be of interest in testing the phenotype of senescent cells and would be useful in screening the role of certain specific genes in cell ageing.

Adolescent

Effects of two K+ channel openers, aprikalim and pinacidil, on hypoxic pulmonary vasoconstriction.

This study investigated the effects of two K+ channel openers, aprikalim and pinacidil, on hypoxic pulmonary vasoconstriction induced in isolated rat lung perfused at constant flow. In order to evaluate the mechanism of the hypoxic vasoconstriction we also studied the effects of an inhibitor of the endothelium-derived relaxing factor (EDRF), NG-nitro-L-arginine methyl ester (100 microM), an inhibitor of the guanylate cyclase, methylene blue (30 microM), two K+ channel blockers, glibenclamide (1 microM) and tetraethylammonium (20 mM). In normoxia, NG-nitro-L-arginine methyl ester, methylene blue, glibenclamide or tetraethylammonium did not enhance significantly the baseline perfusion pressure, suggesting that neither EDRF nor K+ channels are involved in the modulation of the low basal pulmonary vascular tone. In hypoxia, aprikalim and pinacidil (0.03-3 microM) induced a concentration-dependent decrease of pulmonary pressure, exhibiting their spasmolytic effects in acute hypoxia. The hypoxic pressure response was significantly increased by NG-nitro-L-arginine methyl ester, methylene blue and tetraethylammonium, but not by glibenclamide suggesting that EDRF and K+ channels other than ATP-sensitive K+ channels are involved in the modulation of the hypoxic pressure response. The spasmolytic effects of aprikalim and pinacidil (1 microM) were not modified by NG-nitro-L-arginine methyl ester, but were partially reduced by tetraethylammonium and completely abolished by glibenclamide, suggesting that these effects are mainly but not exclusively mediated through ATP-sensitive K+ channel opening.

Animals

In vitro biosynthesis of type I and III collagens by human dermal fibroblasts from donors of increasing age.

A quantitative study of type I and type III collagen production was carried out on primary cultures of human dermal fibroblasts. Cultures were initiated from facial and mammary skin of 29 women aged between 19 and 68 years. Secreted and cell-associated collagen levels were determined by an enzyme linked immunosorbent assay (ELISA). We found that the secretion of type I and type III collagen decreased linearly with age (r = 0.432; P = 0.0193 and r = 0.502; P = 0.0147, respectively). There was a 29% loss in secretion ability for type I and type III collagen over the 49-year period studied. Furthermore, no significant linear age-related decrease was observed for type I and type III collagen associated with the cellular fraction. The influence of body site was also analysed. We observed a significant linear age-related decrease in type I collagen secretion by mammary skin cells (P = 0.0183 and r = 0.618) as well as facial skin cells (P = 0.0037 and r = 0.699). Furthermore, only mammary skin fibroblasts showed a significant linear age-related decrease in secreted type III collagen (P = 0.106 and r = 0.513). No age-related variations in cell-associated collagen were found.

Adult

Influence of asiatic acid, madecassic acid, and asiaticoside on human collagen I synthesis.

Asiatic acid, madecassic acid, and asiaticoside, terpenoids with an ursane skeleton, were tested separately and in combination on skin human fibroblast collagen I synthesis in vitro. In the absence of ascorbic acid, the mixture as well as each individual component stimulated collagen I synthesis to a similar extent. In the presence of ascorbic acid, the level of collagen I secretion was higher for each individual component and for the mixture. A comparison of asiaticoside and asiatic acid shows that the sugar moiety of the molecule does not seem to be necessary for this biological activity.

Adult

A controlled trial of the tolerance of amphotericin B infused in dextrose or in Intralipid in patients with haematological malignancies.

Patients with haematological malignancies requiring an antifungal therapy were randomly assigned to receive amphotericin B diluted in either 5% dextrose or in fat emulsion (Intralipid). Twenty-one patients were included in each group. Mean duration of amphotericin B therapy was 8.4 days in the dextrose group and 12.8 days in the Intralipid group. Amphotericin B infusion induced chills in 16 of 21 patients in the dextrose group and in 5 of 21 in the Intralipid group (P = 0.0008). Serum creatinine increased > 75% from baseline in ten patients in the dextrose group compared with only two in the Intralipid group (P = 0.007). A > or = 50% decrease of creatinine clearance was observed in 14 of 21 patients in the dextrose group compared with seven of 21 patients in the Intralipid group (P = 0.025). No difference was found between the two groups with regard to potassium and sodium requirement. Among patients who did not receive magnesium before antifungal therapy, magnesium supplementation was required more frequently in the dextrose group (8/12 vs 2/11; P = 0.02). Concomitant amikacin dosage reduction was more frequent in the dextrose group due to nephrotoxicity (7/19 vs 2/20; P = 0.045). A similar difference in vancomycin dosage reduction was observed between the two groups (12/20 vs 5/19; P = 0.03).

Adult

[The detection of anti-galactocerebroside autoantibodies in human African trypanosomiasis].

The pathogenesis of the central nervous system (CNS) damage in human african trypanosomiasis (HAT) is unknown. In view of an immunological mechanism, as in another trypanosomiasis, Chagas' disease, the causative agent of which is Trypanosoma cruzi, we have searched autoantibodies directed against glycosphingolipids of CNS. Detection and characterization of autoantibodies were performed by ELISA and detection after thin-layer chromatography of glycolipids with sera of an experimental model of HAT in sheep and sera of patients suffering of HAT from Côte d'Ivoire and Congo. The predominant reactivity of these sera, was characterized with galactocerebrosides, the major glycolipids of the myelin. Autoantibodies were detected in 42.8% and 25% of patients' sera, respectively from Côte d'Ivoire and Congo. The proportion of these antibodies increased dramatically to 72% in sera of patients with neurological symptoms. Anti-galactocerebroside antibodies were also found in CSF of 24.4% of Congolense patients. The pathogenic significance of these anti-galactocerebroside antibodies remains to be determined. They may constitute a predicative marker for the neurological improvement in HAT.

Animals

[An efficacy trial on Trypanosoma brucei brucei of molecules permeating the blood-brain barrier and of megazol].

Human African trypanosomiasis (HAT) is a major public health problem in 36 sub-Saharan African countries and around 50 million people are classed as "at risk". About 25,000 new cases of the disease are reported annually by the World Health Organisation (WHO). This disease is fatal if untreated. As for now, chemotherapy is unsatisfactory and relies on a few drugs which show two major problems. The first is pharmacokinetics involving the passage through the blood-brain barrier. The second concerns toxicity and adverse side-effects of drugs used to treat this disease. New trypanocides should be safe, effective without toxicity. This study reports the action of 45 drugs, known to pass through the blood-brain barrier and belonging to different therapeutic classes, and also the megazol, a nitrothiadiazole derivative, on Trypanosoma brucei brucei AnTat 1-9 in vitro in acellular semi-defined medium. Results showed that some drugs did not modify the parasitic growth, and others were either trypanostatic or trypanocide. These last drugs were tested in vivo on T. b. brucei An-Tat 1-9 infected Swiss mice. Only megazol was shown to be effective and trypanocide. This compound might trigger the production of oxygen derivatives and free radicals-which have toxic effects on the trypanosome metabolism.

Africa South of the Sahara

Disruptions in the secretion of cortisol, prolactin, and certain cytokines in human African trypanosomiasis patients.

It has been shown previously that sleeping sickness at the stage of meningoencephalitis manifests itself as a significant disturbance in the circadian rhythm of sleep-wakefulness. The objective of the current study was to examine the extent of circadian disruption in infected patients by measuring 24 hours patterns of plasma cortisol, an example of a classical circadian rhythm relatively independent of sleep, and prolactin, a primarily sleep-related rhythm. Plasma levels of certain cytokines were also measured to examine the immunopathogenesis of human African trypanosomiasis. An attempt was made to relate any circadian disruptions to the severity of the disease. The three most advanced patients demonstrated circadian disruptions in cortisol, prolactin and sleep-wake rhythms. The prime cytokine factor that correlated with the progression of the disease in humans was interferon-gamma, levels being 7- to 12-fold higher in the patients without any circadian rhythms. Our findings support the hypothesis that human African trypanosomiasis induces selective changes in the suprachiasmatic nucleus, important as a pacemaker for biological rhythms, resulting in disruptions of circadian rhythmicity in advanced stages of the disease.

Adolescent

[The nyctohemeral rhythm of melatonin is preserved in human African trypanosomiasis].

We studied plasma melatonin profiles by radioimmunoassay in nine patients suffering from human african trypanosomiasis and six healthy controls matched according to the age and the photoperiodic conditions. The circadian periodicity of the sleep-wake cycle was disturbed proportionally to the degree of severity of the disease. On the contrary, the patients' plasma melatonin profile was similar to the controls' one. These results suggest that, beside the master clock generating the main circadian rhythms (sleep-wake, melatonin and core temperature rhythms), an additional regulating system of the melatonin rhythm could be involved.

Adolescent

[Maintenance of the relation between the pulsed secretion of hormones and the internal sleep structure in human African trypanosomiasis].

In order to determine whether sleep disturbances would affect the hormonal patterns and the normal relationships between hormone pulses and sleep stages, the 24-hour profiles of cortisol, prolactin and plasma renin activity (PRA) were analysed in 6 sleeping sickness patients studied at Brazzaville and in 5 healthy African controls studied in Abidjan. Polysomnographic recordings were done continuously and blood was taken every 10 minutes throughout the 24-hour period. Plasma was analyzed for cortisol, prolactin and PRA. The circadian rhythm of cortisol, considered as an example of an endogenous rhythm was attenuated in all the patients but one, but as in normal subjects, slow wave sleep (SWS) remained associated with the declining phases of the secretory episodes. Prolactin and PRA profiles, which are strongly influenced by the sleep-wake cycle did not show the increase normally associated with long sleep periods and reflected the spreading of sleep and wakefulness throughout the 24-hour period. However, rapid-eye movement (REM) sleep began in sleeping sickness patients, as in normal subjects, during the descending phases of prolactin pulses. In both groups, PRA reflected the sleep stage distribution with non rapid-eye movement (NREM) sleep occurring during the ascending phases and REM sleep during the descending phases of the oscillations. However, in sleeping sickness patients, the marked sleep fragmentation often did not allow sufficient time for PRA to increase significantly, as observed with regular NREM-REM sleep cycles. These results demonstrate that, together with the disruption of the sleep-wake cycle, there are profound differences in the temporal organization of the 24 hour hormone profiles in human African trypanosomiasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies