Biomedical subjects

M Dumas

Publications and source records attributed to M Dumas.

At least 37 records · Page 2Linked to original sources

PubMed2001

Hypoxic vasoconstriction of rat main pulmonary artery: role of endogenous nitric oxide, potassium channels, and phosphodiesterase inhibition.

This study investigated the influence of NO, potassium (K+) channel blockade, and the phosphodiesterase inhibitors (PDEIs) theophylline (non-selective PDEI), siguazodan (PDE3I), rolipram (PDE4I), and zaprinast (PDE5I) on rat isolated main pulmonary artery hypoxic (95% N2 and 5% CO2) vasoconstriction. Hypoxic vasoconstriction increased by 27% (p < 0.01) in the presence of the NO synthase inhibitor L-NAME (10(-4) M), and by 15% (p < 0.05) in the presence of the K(ATP) channel blocker glibenclamide (10(-6) M), without potentiation by the combination of these two drugs. Hypoxic vasoconstriction decreased by 28% (p < 0.01) in presence of the Kv,-voltage-dependent channel blocker 4-aminopyridine (10(-3) M), whereas the other K+ channel blockers, charybdotoxin (BKCa, large-conductance Ca2+-sensitive K+ channels) and apamin (SKCa, small-conductance Ca2+-sensitive K+ channels) had no effect. The nonselective PDEI theophylline induced a concentration-dependent relaxation (pD2 = 4.05, Emax = 90% [expressed as a percentage of maximal relaxation induced by papaverine 10(-4) M]). Among the selective PDEIs, siguazodan was significantly (p < 0.01) more efficient than rolipram and zaprinast (Emax values were 84%, 67%, and 58%, respectively) and significantly (p < 0.05) more potent than zaprinast (pD2 values were 6.48, 6.34, and 6.16 for siguazodan, rolipram, and zaprinast). Glibenclamide and L-NAME significantly (p < 0.05) shifted the concentration-response curve (CRC) for zaprinast to the right, and L-NAME shifted the CRC significantly to the right for siguazodan. In the presence of L-NAME, glibenclamide had no effect on the CRC of zaprinast. We conclude that (a) NO exerts a permanent inhibitory effect against hypoxic vasoconstriction that might be mediated in part by an activation of K(ATP) channels; (b) a 4-aminopyridine-sensitive K+ channel is involved in vasoconstriction under hypoxic conditions; (c) PDEs 3 and 5 are the predominant PDE isoforms in rat pulmonary artery relaxation; and (d) NO and K(ATP), but neither BK(Ca), SK(Ca), nor Kv channels, are involved in the relaxant effect of PDEIs.

Animals↗

PubMed2001

[Sleeping sickness: major disorders of circadian rhythm].

At the meningoencephalitis stage, human African trypanosomiasis (HAT), sleeping sickness, causes dysregulation of the circadian rhythm of the sleep/wake cycle, rather than hypersomnia. In bedridden patients, total sleep time does not exceed 9 hours. The change in the 24-hour distribution of sleep and wakefulness is proportional to severity of clinical symptoms and laboratory abnormalities. The internal structure of sleep is also altered. All patients present sleep onset rapid eye movement periods (SOREMP), i.e., several sleep episodes beginning with rapid eye movement (REM) sleep. In mild cases, treatment with melarsoprol reverses circadian dysregulation, and SOREMP either decrease in number or disappear. Other circadian disturbances may be observed in HAT. These may include circadian dysrhythmia of hormonal secretions, but the relationship between hormonal pulses and sleep/wake states is preserved. The circadian rhythm of secretion of prolactin, renin, growth hormone and cortisol disappears in severe cases, but persists in mild ones. The amplitude and mean 24-hour value of plasma melatonin are normal with nocturnal peaks and no diurnal secretion. However, peak melatonin secretion occurs 2 hours earlier than in healthy African controls. In conclusion, HAT-induced dysregulation of circadian rhythm is proportional to disease severity. Presence of SOREMP and precocity of peak melatonin secretion support disturbance of the serotoninergic network rather than direct action on the biological clock.

Circadian Rhythm↗

PubMed2000

Inducible nitric oxide synthase and nitrotyrosine in the central nervous system of mice chronically infected with Trypanosoma brucei brucei.

Human African trypanosomiasis, or sleeping sickness, evolves toward a meningoencephalitic stage, with a breakage in the blood-brain barrier, perivascular infiltrates, and astrocytosis. The involvement of nitric oxide (NO) has been evoked in the pathogenic development of the illness, since NO was found to be increased in the brain of animals infected with Trypanosoma brucei (T. b.) brucei. An excessive NO production can lead to alterations of neuronal signaling and to cell damage through the cytotoxicity of NO and its derivatives, especially peroxynitrites. In African trypanosomiasis, the sites of NO production and its role in the pathogenicity of lesions in the central nervous system (CNS) are unknown. In a chronic model of African trypanosomiasis (mice infected with T. b. brucei surviving with episodic suramin administration), NADPH-diaphorase staining of brain slides revealed that NO synthase (NOS) activity is located not only in endothelial cells, choroid plexus ependymal cells, and neurons as in control mice but also in mononuclear inflammatory cells located in perivascular and parenchyma infiltrates. An immunohistochemical study showed that the mononuclear inflammatory cells expressed an inducible NOS activity. Furthermore, the presence of nitrotyrosine in inflammatory lesions demonstrated an increased NO production and the intermediate formation of peroxynitrites. The detection of extensive formation of nitrotyrosine in the CNS parenchyma was observed in mice having shown neurological disorders, suggesting the role of peroxynitrites in the appearance of neurological troubles. In conclusion, this study confirmed the increased NO synthesis in the CNS of mice infected with T. b. brucei and suggests a deleterious role for NO, through the formation of peroxynitrites, in the pathogenesis of African CNS trypanosomiasis.

Animals↗

PubMed2000

Inhibition by SR 59119A of isoprenaline-, forskolin- and VIP-induced relaxation of human isolated bronchi.

In the human isolated bronchus (HIB) it has been shown that beta(3)-adrenoceptor stimulation fails to induce relaxation of airway smooth muscle. It has however been reported in human ventricular endomyocardial biopsies that beta(3)-adrenoceptor stimulation induced a marked negative inotropic effect which could be linked to Gi protein activation. The aims of this study were: (1) to determine in HIB (internal diameter 1-2 mm) whether the selective beta(3)-adrenoceptor agonist SR 59119A (N[7-methoxy-1,2,3, 4-tetrahydronaphthalen-(2R)methyl]-(2R)-2-hydroxy-2-(3-chloroph eny l)e thanamine hydrochloride) was able to inhibit adenylate-cyclase-mediated airway smooth muscle relaxation induced by isoprenaline, forskolin or vasoactive intestinal peptide (VIP) and (2) to investigate the role of the Gi protein in this interaction. SR 59119A (0.1 microM and 1 microM) induced a shift to the right of concentration response curve for isoprenaline (-0. 15+/-0.06 and -0.54+/-0.21 log unit, P<0.05 and P<0.01 respectively), forskolin (-0.12+/-0.02 and -0.30+/-0.05 log unit, P<0.001), and VIP (-0.42+/-0.12 log unit, P<0.01 with SR59119A 10(-6)M). The inhibitory effect of SR 59119A was (1) abolished by an incubation of HIB with pertussis toxin (1 microg/ml, during 15 h in Krebs-Henseleit solution, at 21 degrees C), which is known to inactivate the Gi protein and (2) increased after an incubation of HIB with the pro-inflammatory cytokine IL-1beta (10 ng/ml, during 15 h in Krebs-Henseleit solution, at 21 degrees C), which is known to up-regulate Gi protein expression. Our results suggest that the selective beta(3)-adrenoceptor agonist SR59119A might inhibit the cAMP-dependent relaxation of human isolated bronchus through Gi protein-mediated inhibition of adenylate cyclase.

Adenosine Monophosphate↗

PubMed2000

Estimation of the amyotrophic lateral sclerosis incidence by capture-recapture method in the Limousin region of France.

Amyotrophic lateral sclerosis (ALS) is a rapidly fatal degenerative neurological disease categorized among motor neuron diseases. In the literature, the incidence of ALS varies between 0.7 and 2.4 per 100, 000 inhabitants. A study using the capture-recapture method (multiple records system analysis) was undertaken in Limousin (France) ascertaining all patients having onset of definite or probable ALS during the period 1994-1995. Three information sources able to identify these new ALS cases were selected: the first source was a computerized database of the Neurology Department of the University Hospital of Limoges; the second source consisted of the neurologists of the Limousin region and neighboring provinces (county-sized regions); the third source grouped the hospitals of the Limousin region and neighboring provinces (county-sized regions). During this period, 46 new cases of ALS were seen, corresponding to an observed mean annual incidence of 3.2 (+/-0.6) per 100,000 inhabitants. After standardization for age, the annual incidence was 2.5 per 100,000 inhabitants. The number of new cases estimated by the capture-recapture method was 70, corresponding to an estimated mean annual incidence of 4.9 (+/-1.0) for 100,000 inhabitants. Hence, statistical modeling utilizing partially overlapping information sources permitted a more exhaustive compendium of the new cases of ALS and may be a truer reflection of actual disease incidence than has been previously reported.

Amyotrophic Lateral Sclerosis↗

PubMed2000

Functional, biochemical and molecular biological evidence for a possible beta(3)-adrenoceptor in human near-term myometrium.

The possible existence of a beta(3)-adrenoceptor (beta(3)-AR) in human near-term myometrium was investigated by in vitro functional and biochemical studies and analysis of mRNA expression. SR 59119A and SR 59104A and CGP 12177 (two selective agonists and a partial agonist, respectively, of the beta(3)-AR), salbutamol and terbutaline (beta(2)-AR agonists) each produced a concentration-dependent relaxation of the myometrial spontaneous contractions. There were no differences in pD(2) values for the relaxing potencies of terbutaline, salbutamol, CGP 12177 and SR 59119A. The rank order for their relaxing efficacies was SR 59119A>SR 59104A>terbutaline approximately salbutamol approximately CGP 12177 (E(max)=52+/-7%, 42+/-12% and approximately 30% respectively). Propranolol, a beta(1)- and beta(2)-AR antagonist, and ICI 118551, a beta(2)-AR antagonist (both at 0.1 microM), did not affect the SR 59119A-induced relaxation whereas SR 59230A, a selective beta(3)-AR antagonist (1 microM), significantly reduced the maximal relaxing effect of SR 59119A. SR 59119A and salbutamol induced a significant increase in cyclic AMP levels that was antagonized by SR 59230A but not by propranolol for SR 59119A, and by propranolol but not by SR 59230A for salbutamol. The beta(3)-AR mRNA was positively expressed in myometrium preparations in a reverse transcription polymerase chain assay. The results presented provide the first evidence for the existence of the beta(3)-AR subtype in human near-term myometrium and suggest that the effects of SR 59119A might be mediated through an increase in cyclic AMP level.

Adrenergic beta-Agonists↗

PubMed2000

In vitro induction of nitric oxide synthase in astrocytes and microglia by Trypanosoma brucei brucei.

In stage II human african trypanosomiasis (HAT), which is characterized by central nervous system (CNS) involvement, neurones and oligodendrocytes might be targets of dysimmune processes. Nitric oxide (NO) production by peripheral macrophages is documented in HAT. We studied the production of NO by murine astrocytes and microglia cocultured with Trypanosoma brucei (T. b.) brucei AnTat 1.9. Purified astrocytes or microglia from mouse brains were cocultured with T. b. brucei, and in some instances with interferon (IFN)-gamma, which is known to be released during the disease and also to be a growth factor for trypanosomes. Inducible NO synthase (iNOS) expression was studied by indirect immunofluorescence and reverse transcriptase-polymerase chain reaction. NO production was determined by measuring nitrite generation in culture. Detection of iNOS in astrocytes and microglia in the presence of T. b. brucei, was closely associated with nitrite production and was strongly enhanced by the addition of IFN-gamma to the culture medium. The stimulation of iNOS activity required parasite-cell contact and likely occurred at the transcriptional level. This study demonstrates the induction of iNOS in CNS-related macrophage cells in the presence of trypanosomes and its potentiation by IFN-gamma.

Animals↗

PubMed2000

The protective role of Langerhans' cells and sunlight in multiple sclerosis.

The low prevalence of multiple sclerosis in equatorial areas may be the consequence of a physiological immunosuppression induced by ultraviolet radiation on the epidermal Langerhans' cells, which are the antigen-presenting cells. Multiple sclerosis appears to be the consequence of an immune response to an environmental antigen during childhood in the absence of two protective factors: a genetic factor conferred by the HLA haplotypes of Langerhans' cells, and an environmental factor conferred by ultraviolet radiation in sunlight. In the presence of these two factors, T lymphocytes are physiologically immunosuppressed. Their association may play a key role in protection against multiple sclerosis. The varying combinations of these two factors may provide an explanation for the differences in incidence and prevalence of the disease noted within a single region or from one region to another throughout the globe. The hypothetical pathogenic mechanism developed in this article opens up new fields of research, particularly those concerning its therapeutic applications.

Humans↗

PubMed2000

Pharmacokinetics, metabolism and excretion of megazol in a Trypanosoma brucei gambiense primate model of human African trypanosomiasis. Preliminary study.

The pharmacokinetics of megazol (2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol, CAS 19622-55-0) was investigated after a 100 mg/kg oral administration to six primates infected with Trypanosoma brucei gambiense. The plasma levels of megazol were between 0.2 microgram/ml and 46 micrograms/ml 24 h after dosing in all animals. In animals with prolonged infection, megazol absorption was accelerated (Tmax was 4 h compared with 8 h, for day 53 and day 39 post inoculation) but the amount absorbed was not modified. The megazol concentrations in the cerebrospinal fluid represented between 5.5% and 10.6% of the plasma levels at the same times. Unchanged megazol was eliminated predominantly via the kidneys: 46-96% of the ingested dose was recovered in the urine, compared with 0-5% in the faeces. Furthermore, this urinary elimination of megazol was altered in animals with prolonged infections. In the urine, 4 unknown metabolites were observed, unchanged megazol was characterized by LC-MS/MS. This study indicates that megazol crosses the blood-brain barrier after oral administration. Prolonged infections affect the absorption of megazol and its urinary elimination.

Animals↗

PubMed2000

Estimation of the prevalence of epilepsy in the Benin region of Zinvié using the capture-recapture method.

BACKGROUND: The prevalence of epilepsy was estimated in two villages of 3134 inhabitants, in Benin, in April and May 1997 using the capture-recapture method. METHODS: Information was obtained from (i) a door-to-door cross-sectional study, (ii) a non-medical source consisting of key informants (traditional practitioners, teachers, village leaders, and religious representatives) and (iii) a medical source through evaluation of medical records in health centres. In all the three situations, the diagnosis of epilepsy was confirmed by a neurologist. RESULTS: The door-to-door survey found 50 epileptics, i.e. a prevalence of 15.9 per 1000. The non-medical source found 26 patients. The medical source found only four patients. In total, 66 epileptics were found by combining the three sources, giving a prevalence of 21.1 per 1000. After application of the capture-recapture method, the estimated number of cases from the door-to-door survey and non-medical source was 105, and 110 cases when the medical source was considered as well. The respective prevalences were 33.5 per 1000, and 35.1 per 1000. CONCLUSIONS: The door-to-door survey has been usefully improved by using key informants. The epilepsy prevalence estimate found by capture-recapture is clearly higher than that found by traditional cross-sectional methods, and could better depict the frequency of epilepsy in Africa.

Adolescent↗

PubMed2000

Antiepileptic therapies in the Mifi Province in Cameroon.

PURPOSE: To evaluate the availability and accessibility of antiepileptic drugs (AEDs) in two health districts in Cameroon. METHODS: The study included 33 patients with epilepsy, 26 physicians, 13 private pharmacists, eight hospital pharmacists, three distributors, and eight traditional healers. Structured questionnaires were used to assess the knowledge of the disease, treatment accessibility, the methods of prescriptions, and the availability and the frequency of delivery of drugs. RESULTS: Only one of 33 patients did not take modern treatment; 91% of the patients were followed up by a traditional healer, and 78%, by an hospital physician. Phenobarbitone (PB) was the most frequently prescribed drug by 69% of the doctors; 54% of the physicians considered the traditional therapies to be incompatible with modern drug treatment. By pharmacists, PB was delivered regularly. Other drugs went out of stock frequently. The number of packages in stock varied significantly directly with the frequency of delivery. The mean price per package and the mean number of packages in stock were higher in the public hospital pharmacies than in the private pharmacies. A majority of healers explained epilepsy as the presence of excess foam in the abdomen. The remedies proposed were to stop foam secretion. CONCLUSIONS: Availability of AEDs was quite high, but with no strict correspondence between the rate of prescriptions and the supply of the drugs.

Adult↗

PubMed2000

Central brain postembryonic development in Drosophila: implication of genes expressed at the interhemispheric junction.

Postembryonic brain development of Drosophila has become recently a subject of intense investigations. In particular, the linotte (lio) mutants display strong structural defects in the mushroom bodies and the central complex. The Lio kinase is expressed in a glial structure at the interhemispheric junction of late larval and young pupal brain. With the aim of identifying new genes involved in the formation of adult central brain structures, 821 enhancer-trap Gal4 lines were generated and screened for late larval expression. We identified 167 lines showing expression at or near the interhemispheric junction of third-instar larval brain, an area from which the central complex differentiates. Adult brains from 104 of these 167 lines were analyzed through paraffin sections. This secondary screen allowed the recovery of five central brain mutants. Of 89 control lines showing various patterns of expression excluding the interhemispheric junction, only one anatomical mutant was isolated. These six mutations, which have been thoroughly characterized, affect the midline area of the adult brain with phenotypes of split central complex structures and/or fused mushroom body lobes. This work opens the way for further analysis of the molecular and cellular events involved in central brain reorganization during metamorphosis.

Animals↗

PubMed2000

[Case study of 199 patients with multiple sclerosis: the use of EDMUS program].

European Database Multiple Sclerosis (EDMUS) is a standardized tool which allows the collection of clinical, biological, radiological and therapeutic data on multiple sclerosis (MS). A descriptive analysis of 199 patients was done using EDMUS (version 2.2). Most data agreed with previous published results, except a low 0.4 sex ratio. At the beginning of MS, 42 p. 100 of MS patients developed pyramidal and sensory involvements and 14 p. 100 retrobulbar optic neuritis. Optic neuritis was the most frequent initial symptom of relapsing-remitting MS (25.9 p. 100) but not in the chronic progressive form (5.5 p, 100; p < 0.01). Surprisingly, relapsing-remitting form occurred more frequently whereas the secondary progressive form was diagnosed less. The concordances between the three disability scales, EGS (EDMUS Grading Scale), EDSS (Expanded Disability Status Score) and AI (Hauser Ambulation Index) were correct. In clinical practice, EDMUS is user-friendly and rapid. The lack of radiological data and the necessary quantification of only one disability scale, EGS may be too restrictive. The analysis of most of clinical data is possible by using integrated selection within the software, but sometimes needs more complex procedures.

Databases as Topic↗

PubMed2000

[Cysticercosis and epilepsy in the city of Tone, north of Togo].

An epidemiology study was conducted in Tone, a city in the very north of Togo from November 1 to 25, 1995. The prevalence of epilepsy was studied in 9,155 subjects and seroprevalence of cysticercosis in 1,343. This was a representative sample of this region with 194,000 inhabitants. The prevalence of epilepsy was 18.6 per 1 000 inhabitants. A causal relationship was found betwen cysticercosis and epilepsy. The prevalenced of cysticercosis was 38 per 1 000 persons in the general population and 135.29 per 1 000 epileptic patients. The difference was highly statistically significant (X( 2)=74.17, p<10(-6)).

Adult↗

PubMed2000

[Prevalence of HTLV-1 virus infection in Togo (Kozah prefecture and the University Hospital Center of Lomé].

The aim of this study was to determine the prevalence of Human T cell Leukaemia Virus Type 1 (HTLV1) in a representative population sample, in neurological and non-neurological patients hospitalised in the Lomé teaching hospital in order to study the clinical manifestations of this retrovirus. There was no statistical difference among the three groups concerning the prevalence of HTLV1 respectively (1.2%: 21/1717, 1.8%: 15/828 and 1.6%: 4/244). Spastic paraparesis was the only disease significantly linked to HTLV1 (15.5%: 9/58).

Adolescent↗

PubMed2000

[Interest of a computerized ALS database in the diagnosis and follow-up of patients with ALS].

The aim of the study is to present a computerized database of the Neurology department of Limoges University Hospital and the main results obtained from data of 340 patients suffering from amyotrophic lateral sclerosis (ALS), diagnosed between 1984 and 1997. It is a user friendly and can be accessed by all neurologists at any level of computer knowledge. This database is modular (6 modules) and flexible according to need. The software used, Access 7, is an open relation database, which allows export of data to statistical or other compatible software. One of the reasons, which led to the elaboration of this database was to develop a means of collecting data in an analyzable manner for therapeutic trials. During these trials, a great number of data can be collected during each clinic visit for the evaluation of the degree of impairment, disability, and handicap. We present part of the data from the patients followed, some of whom were treated with riluzole, the current reference molecule for ALS.

Aged↗

PubMed2000

A proposal to declare neurocysticercosis an international reportable disease.

Neurocysticercosis is an infection of the nervous system caused by Taenia solium. It is the most important human parasitic neurological disease and a common cause of epilepsy in Africa, Asia, and Latin America, representing enormous costs for anticonvulsants, medical resources and lost production. Neurocysticercosis is a human-to-human infection, acquired by the faecal-enteric route from carriers of intestinal T. solium, most often in areas with deficient sanitation. Intestinal tapeworms cause few symptoms, but adult taeniae carried by humans release large numbers of infective eggs and are extremely contagious. Ingestion of poorly cooked pig meat infested with T. solium larvae results in intestinal taeniosis but not neurocysticercosis. With a view to hastening the control of taeniosis and neurocysticercosis we propose that neurocysticercosis be declared an international reportable disease. New cases of neurocysticercosis should be reported by physicians or hospital administrators to their health ministries. An epidemiological intervention could then be launched to interrupt the chain of transmission by: (1) searching for, treating and reporting the sources of contagion, i.e. human carriers of tapeworms; (2) identifying and treating other exposed contacts; (3) providing health education on parasite transmission and improvement of hygiene and sanitary conditions; and (4) enforcing meat inspection policies and limiting the animal reservoir by treatment of pigs. We believe that the first step required to solve the problem of neurocysticercosis is to implement appropriate surveillance mechanisms under the responsibility of ministries of health. Compulsory notification also has the major advantage of providing accurate quantification of the incidence and prevalence of neurocysticercosis at regional level, thus permitting the rational use of resources in eradication campaigns.

Adolescent↗

PubMed2000

[Sleeping sickness, a reemerging sickness].

Human African Trypanosomiasis (THA) has reappeared in most intertropical countries of Black Africa and an estimated 400,000 new cases are reported every year. Genetic tests which now make possible the differentiation of morphologically similar trypanosome subspecies showed that a large variety of game and domestic animals act as reservoir hosts of Trypanosoma brucei gambiense, thus making it even more difficult to fight the disease. The detection of cases and their treatment are absolutely necessary in preventing the spread of the disease. This can only be carried out with mobile medical teams which seek out patients. This detection currently calls on techniques which isolate trypanosomes and serological techniques. The collection of data with regards to different geographical positions, makes it possible to determine exactly which regions are affected, possibly affected or sound. Although the diagnosis of the hemo-lymphatic stage can be determined without any great problem nowadays, the point at which the trypanosome invades CNS tissues and the ways in which it occurs are as yet unknown, even though the role of nitric oxyde and cytokines is better understood. Antibodies, anti-neurofilaments and anti-galactocerebrosides when found in the cerebro-spinal fluid are characteristic of the nervous stage of the disease. This condition is really sleeping sickness, not only hypersomnia. The more seriously the patient is affected the shorter the sleep-wake cycles are during the nycthemeron. These early disorders can be quickly reversed thanks to therapy, which to day uses melarsoprol, an arsenical drug, which cannot be of great promise as it is very toxic. Current research into nitro-imidazole derivatives (particularly megazol) seems a promising therapy as they were effective in vitro and in vivo, in rodents and primates.

Africa↗