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1.
BMC Immunol ; 22(1): 48, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294032

RESUMO

BACKGROUND: The presence of the human leukocyte antigen HLA-B*57:01 is associated with the development of a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*57:01 prevalence in individuals with HIV-1 in Africa. This study aimed to estimate HLA-B*57:01 prevalence in individuals with HIV-1 in West and Central Africa. METHODS: A cross-sectional study was conducted in four countries in West and central Africa (Burkina-Faso, Côte d'Ivoire, Gabon, and Togo) from January 2016 to February 2020 to determine the status of HLA-B*57:01 in adults with HIV-1. The presence of HLA-B*57:01 was determined by using Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) in blood samples. Prevalence rates were stratified based on country. RESULTS: A total of 4016 (69.8% women) individuals with HIV were enrolled. Their median age was 45, and the interquartile range was 38-52. We included 500 (12.4%) patients in Burkina-Faso, 1453 (36.2%) in Côte d'Ivoire, 951 (23.7%) in Gabon, and 1112 (27.7%) in Togo. The overall HLA-B*57:01 prevalence was 0.1% [95% CI: 0.0-0.2%]. The prevalence of HLA-B*57:01 was similar according to the four countries. Only one case was reported in each country except Togo, with no cases. CONCLUSIONS: HLA-B*57:01 prevalence is low in individuals with HIV in West and central Africa, and there is no difference among countries. This study does not confirm the utility of HLA-B*57:01 allele testing for abacavir use in this region.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/diagnóstico , Genótipo , Infecções por HIV/imunologia , HIV-1/fisiologia , Antígenos HLA-B/genética , Adulto , África Central/epidemiologia , África Ocidental/epidemiologia , Hipersensibilidade a Drogas/etiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Humanos , Pessoa de Meia-Idade , Prevalência
2.
Drug Discov Today ; 23(2): 409-415, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29031622

RESUMO

Protein kinases constitute a large group of enzymes in eukaryotes and have an important role in many cellular processes. Several of these proteins are active kinases, such as haploid germ cell-specific nuclear protein kinase (Haspin), an atypical eukaryotic protein kinase that lacks sequence similarity with other eukaryotic protein kinases. Haspin is a serine/threonine kinase that associates with chromosome and phosphorylates threonine 3 of histone 3 during mitosis. Haspin overexpression or deletion results in defective mitosis. It has been shown that Haspin inhibitors have potent anti-tumoral effects. Given that the only Haspin substrate is threonine 3 of histone 3, inhibition of Haspin might have fewer adverse effects compared with other anticancer agents. Here, we highlight the chemical structures and actions of currently known Haspin inhibitors.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Cromossomos/efeitos dos fármacos , Histonas/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo
3.
Artigo em Francês | AIM (África) | ID: biblio-1264188

RESUMO

La malnutrition chez les enfants a atteint des proportions inquiétantes dans les pays en voie de développement y compris le Bénin. Cette étude s'est inscrite dans le cadre de la lutte contre les carences en nutriments, dans la mesure où promouvoir des farines infantiles de bonne qualité nutritionnelle semble être l'une des meilleures voies d'amélioration du statut nutritionnel du jeune enfant. L'objectif était d'évaluer la qualité nutritionnelle des farines infantiles commercialisées au Bénin. Il s'agissait d'une étude transversale qui a porté sur 10 farines de 2ème âge, dont 8 locales et 2 importées, considérées comme référence. Les teneurs en nutriments ont été évaluées en suivant les méthodes de dosage de référence. Les résultats ont montré une non-conformité de la composition de ces farines aux normes du Codex Alimentarius, sauf en ce qui concerne les teneurs en énergie et en protéine. Sur le plan qualitatif, les protéines apportées par ces aliments de complément sont uniquement végétales, contrairement aux proportions recommandées de 6% d'origine végétale et 6% d'origine animale. Malgré l'ajout de compléments vitaminiques, les farines analysées sont très pauvres en micronutriments. En outre, une densité énergétique inadéquate des bouillies issues de la préparation de certaines farines les rend incapables d'assurer une alimentation suffisante pour la croissance du jeune enfant. Il ressort néanmoins, une standardisation des méthodes de fabrication de ces aliments de complément, expliquant l'absence de variation des paramètres étudiés d'un lot à un autre, à l'exception de la teneur en matières sèches. Des propositions d'amélioration de la densité énergétique des bouillies, ainsi que de la formulation des recettes et de leur préparation ont été suggérées à l'égard des entreprises productrices de farines infantiles de complément au Bénin


Assuntos
Benin , Criança , Farinha/efeitos adversos , Farinha/normas , Desnutrição
4.
PLoS One ; 12(8): e0179211, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28796777

RESUMO

Lipid nanocapsules (LNCs) are biomimetic nanocarriers used for the encapsulation of a broad variety of active ingredients. Similar to surface active compounds, LNCs contain both hydrophilic and hydrophobic parts in their structure. Moreover, the components of LNCs, macrogol 15 hydroxystearate (MHS) and lecithin, are known for their surface active properties. Therefore, the aim of this paper was to investigate the capability of the LNCs to decrease surface tension using two techniques: drop tensiometry and the Wilhelmy plate method. LNCs with diameters ranging from 30 to 100 nm were successfully obtained using a phase inversion technique. The LNCs' properties, such as size and zeta potential, depend on the composition. LNCs exhibit a lower limiting surface tension compared to MHS (34.8-35.0 mN/m and 37.7-38.8 mN/m, respectively), as confirmed by both drop tensiometry and the Wilhelmy plate method. LNCs have exhibited a saturated interfacial concentration (SIC) that was 10-fold higher than the critical micellar concentration (CMC) of MHS or the SIC of binary and ternary mixtures of LNC ingredients. The SIC of the LNC formulations depended on the mass mixing ratio of the MHS/triglycerides but not on the presence of lecithin. The CMC/SIC values measured by the Wilhelmy plate method were higher than those obtained using drop tensiometry because of the longer duration of the tensiometry measurement. In conclusion, the surfactant-like properties of the LNCs offer new possibilities for medical and pharmaceutical applications.


Assuntos
Lipídeos/química , Nanocápsulas/química , Lecitinas/química , Micelas , Polietilenoglicóis/química , Glycine max/química , Estearatos/química , Propriedades de Superfície , Tensão Superficial
5.
Nutrition ; 33: 35-41, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27908548

RESUMO

OBJECTIVES: Hypertension is highly prevalent in West African populations, but little data is available on salt and potassium intake in these populations. We assumed in this study that sodium and potassium intake might be high and low, respectively, in the Beninese population in view of the emerging nutritional transition. The aim of this study was to estimate dietary sodium and potassium intakes based on 24-h urine collections. METHODS: We selected 420 individuals (ages 25-64 y), representative of the population, from urban and rural areas in Benin. Urine was collected over 24 h, and sodium, potassium, and creatinine were quantified. Blood pressure was measured on the left arm using a validated electronic oscillometric monitor. RESULTS: Adequate data were available for 354 participants. Mean dietary intake of sodium and potassium were 4.4 ± 2.1 and 1.8 ± 0.9 g/24 h, respectively. High intake of sodium was associated with urban area, age <44 y, administrative occupation, higher income, body mass index (BMI) ≥25 kg/m2, and a large waist circumference. High potassium intake was associated with male sex, administrative occupation, BMI ≥25 kg/m2, and large waist circumference. Sodium intake was associated with high systolic and diastolic blood pressures. In multivariate analysis, only age <44 y and, marginally, BMI ≥25 kg/m2 were associated with high sodium intake, whereas male sex and a BMI ≥25 kg/m2 were associated with high potassium intake. CONCLUSION: Large proportions of the population had sodium intake higher, and potassium intake lower, than dietary recommendations. These results suggest that interventions to reduce salt consumption and promote potassium-rich foods, including fruits and vegetables, are needed in Benin.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Dieta , Hipertensão/etiologia , Potássio na Dieta/administração & dosagem , Potássio/administração & dosagem , Sódio na Dieta/administração & dosagem , Sódio/administração & dosagem , Adulto , Benin , Índice de Massa Corporal , Comportamento Alimentar , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Potássio/urina , Potássio na Dieta/urina , Recomendações Nutricionais , Fatores Sexuais , Sódio/urina , Sódio na Dieta/farmacologia , Sódio na Dieta/urina , População Urbana , Circunferência da Cintura
6.
Malar J ; 15(1): 570, 2016 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-27887647

RESUMO

BACKGROUND: Plasmodium vivax is considered to be absent from western Africa, where the prevalence of Duffy-negative red blood cell phenotype proves to be high. Several studies have, however, detected P. vivax infection cases in this part of Africa, raising the question of what is the actual prevalence of P. vivax in local populations. METHODS: The presence of P. vivax was investigated in a large population of healthy blood donors in Benin using microscopy, serology and molecular detection. The seroprevalence was measured with species-specific ELISA using two recombinant P. vivax proteins, namely rPvMSP1 and rPvCSP1. Specific molecular diagnosis of P. vivax infection was carried out using nested-PCR. The performances and cut-off values of both rPvCSP1 and rPvMSP1 ELISA were first assessed using sera from P. vivax-infected patients and from non-exposed subjects. RESULTS: Among 1234 Beninese blood donors, no parasites were detected when using microscopy, whereas 28.7% (354/1234) of patients exhibited had antibodies against rPvMSP1, 21.6% (266/1234) against rPvCSP1, and 15.2% (187/1234) against both. Eighty-four samples were selected for nested-PCR analyses, of which 13 were positive for P. vivax nested-PCR and all Duffy negative. CONCLUSION: The results of the present study highlight an unexpectedly high exposure of Beninese subjects to P. vivax, resulting in sub-microscopic infections. This suggests a probably underestimated and insidious parasite presence in western Africa. While the vaccination campaigns and therapeutic efforts are all focused on Plasmodium falciparum, it is also essential to consider the epidemiological impact of P. vivax.


Assuntos
Anticorpos Antiprotozoários/sangue , Infecções Assintomáticas/epidemiologia , Malária Vivax/epidemiologia , Malária Vivax/patologia , Benin/epidemiologia , Doadores de Sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , Estudos Soroepidemiológicos
7.
Nutrition ; 32(5): 560-5, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26796150

RESUMO

OBJECTIVE: Iodine deficiency has severe pathological repercussions. The aim of this study was to evaluate iodine intake and status in adults in Benin, West Africa. METHODS: We randomly selected 420 participants ages 25 to 64 y and free of visible goiter from urban and rural settings of South Benin. The participants had a diet based on carbohydrates and fish. Urine was collected over a 24-h period and samples were assayed for iodine analysis using inductively coupled plasma mass spectrometry. RESULTS: We studied 401 urinary iodine samples. The overall median urinary iodine concentration (UIC) in 24-h urine was 62.9 µg/L (interquartile range: 40-96.2 µg/L). UIC was significantly lower in women than men (56.5 versus 78.6 µg/L; P < 0.001) and in rural versus urban areas (54.7 versus 77.8 µg/L; P < 0.001). In multivariate analysis, low UIC (<100 µg/L) was positively associated with women (odds ratio, 2.48; 95% confidence interval, 1.44-4.26; P = 0.001) and body mass index <25 kg/m(2) (odds ratio, 2.06; 95% confidence interval, 1.20-3.54; P = 0.008). CONCLUSION: Iodine intake appeared to be fairly low in the Beninese population, according to World Health Organization criteria, and factors associated with low iodine intake were identified. Public health interventions to increase iodine intake, such as iodization of commercial salt and/or fortification of selected nutrients, should be strengthened at the national level.


Assuntos
Deficiências Nutricionais/etiologia , Dieta/efeitos adversos , Iodo/administração & dosagem , Estado Nutricional , Saúde da População Rural , Saúde da População Urbana , Adulto , Benin/epidemiologia , Índice de Massa Corporal , Deficiências Nutricionais/epidemiologia , Deficiências Nutricionais/etnologia , Deficiências Nutricionais/urina , Países em Desenvolvimento , Dieta/etnologia , Feminino , Humanos , Incidência , Iodo/deficiência , Iodo/urina , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Análise Multivariada , Inquéritos Nutricionais , Estado Nutricional/etnologia , Saúde da População Rural/etnologia , Fatores Sexuais , Espectrofotometria Atômica , Saúde da População Urbana/etnologia
8.
J Clin Hypertens (Greenwich) ; 18(7): 634-40, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26530545

RESUMO

The 24-hour urine collection method is considered the gold standard for the estimation of ingested potassium and sodium. Because of the impracticalities of collecting all urine over a 24-hour period, spot urine is often used for epidemiological investigations. This study aims to assess the agreement between spot urine and 24-hour urine measurements to determine sodium and potassium intake. A total of 402 participants aged 25 to 64 years were randomly selected in South Benin. Spot urine was taken during the second urination of the day. Twenty-four-hour urine was also collected. Samples (2-mL) were taken and then stored at -20°C. The analysis was carried out using potentiometric dosage. The agreement between spot urine and 24-hour urine measurements was established using Bland-Altman plots. A total of 354 results were analyzed. Daily sodium chloride and potassium chloride urinary excretion means were 10.2±4.9 g/24 h and 2.9±1.4 g/24 h, respectively. Estimated daily sodium chloride and potassium chloride means from the spot urine were 10.7±7.0 g/24 h and 3.9±2.1 g/24 h, respectively. Concordance coefficients were 0.61 at d=-0.5 g, (d±2SD=-11 g and 10.1 g) for sodium chloride and 0.61 at d=-1 g, (d±2SD=-3.8 g and 1.8 g) for potassium chloride. Spot urine method is acceptable for estimating 24-hour urinary sodium and potassium excretion to assess sodium and potassium intake in a black population. However, the confidence interval for the mean difference, which is too large, makes the sodium chloride results inadmissible at a clinical level.


Assuntos
Cloreto de Potássio/urina , Cloreto de Sódio/urina , Coleta de Urina/métodos , Adulto , Benin , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de Tempo
9.
Biomed Res Int ; 2015: 835767, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26180813

RESUMO

Buruli ulcer (BU) imposes a serious economic burden on affected households and on health systems that are involved in diagnosing the disease and treating patients. Research is needed to find cost-effective therapies for this costly disease. Plants have always been an important source of new pharmacologically active molecules. Consequently we decided to undertake the study of plants used in traditional treatment of BU in Benin and investigate their antimycobacterial activity as well as their chemical composition. Extracts from forty-four (44) plant species were selected on account of reported traditional uses for the treatment of BU in Benin and were assayed for antimycobacterial activities. Crude hydroethanolic extract from aerial parts of Holarrhena floribunda (G. Don) T. Durand and Schinz was found to have significant antimycobacterial activity against M. ulcerans (MIC = 125 µg/mL). We describe here the identification of four steroidal alkaloids from Mycobacterium ulcerans growth-inhibiting fractions of the alkaloidal extract of the aerial parts of Holarrhena floribunda. Holadysamine was purified in sufficient amount to allow the determination of its MCI (=50 µg/mL). These results give some support to the use of this plant in traditional medicine.


Assuntos
Alcaloides , Antibacterianos , Úlcera de Buruli/tratamento farmacológico , Holarrhena/química , Mycobacterium ulcerans/crescimento & desenvolvimento , Plantas Medicinais/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Humanos , Medicinas Tradicionais Africanas
10.
Int J Pharm ; 493(1-2): 224-32, 2015 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-26183331

RESUMO

Inhaled fluticasone propionate (FP) is often prescribed as a first-line therapy for the effective management of pulmonary diseases such as asthma. As nanocarriers offer many advantages over other drug delivery systems, this study investigated the suitability of lipid nanocapsules (LNCs) as a carrier for fluticasone propionate, examining the drug-related factors that should be considered in the formulation design and the behaviour of LNCs with different compositions and properties suspended within aerosol droplets under the relatively hostile conditions of nebulization. By adjusting the formulation conditions, particularly the nanocarrier composition, FP was efficiently encapsulated within the LNCs with a yield of up to 97%, and a concentration comparable to commercially available preparations was achieved. Moreover, testing the solubility of the drug in oil and water and determining the oil/water partition coefficient proved to be useful when assessing the encapsulation of the FP in the LNC formulation. Nebulization did not cause the FP to leak from the formulation, and no phase separation was observed after nebulization. LNCs with a diameter of 100 nm containing a smaller amount of surfactant and a larger amount of oil provided a better FP-loading capacity and better stability during nebulization than 30 or 60 nm LNCs.


Assuntos
Portadores de Fármacos/química , Fluticasona/química , Nanocápsulas/química , Antialérgicos/química , Broncodilatadores/química , Química Farmacêutica , Estabilidade de Medicamentos , Lecitinas/química , Nebulizadores e Vaporizadores , Polietilenoglicóis/química , Solubilidade , Ácidos Esteáricos/química , Triglicerídeos/química
11.
Malar J ; 13: 240, 2014 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-24946685

RESUMO

BACKGROUND: Malaria Is A Life-Threatening Pathology In Africa. Plasmodium Falciparum And Plasmodium Vivax Attract The Most Focus Because Of Their High Prevalence And Mortality. Knowledge About The Prevalence Of The Cryptic Pathogens Plasmodium Ovale And Plasmodium Malariae Is Limited. Thanks To Recombinant Tools, Their Seroprevalence Was Measured For The First Time, As Well As The Prevalence Of Mixed Infections In A Malaria-Asymptomatic Population In Benin, A Malaria-Endemic Country. METHODS: A Panel Of 1,235 Blood Donations Collected Over Ten Months In Benin Was Used For Validation Of The Recombinant Tools. Recombinant P. Falciparum, P. Malariae, P. Ovale MSP1, And P. Falciparum AMA1 Were Engineered And Validated On A Biobank With Malaria-Infected Patients (N = 144) Using A Species-Speific ELISA Test (Recelisa). Results Were Compared To An ELISA Using A Native P. Falciparum Antigen (NatELISA). RESULTS: Among Microscopically Negative African Blood Donors, 85% (1,050/1,235) Present Antibodies Directed To Native P. Falciparum, 94.4% (1,166/1,235) To rPfMSP1 And rPfAMA1, 56.8% (702/1,235) To rPoMSP1, 67.5% (834/1235) To rPmMSP1 And 45.3% Of The Malaria Seropositive Population Had Antibodies Recognizing The Three Species. CONCLUSION: A High Rate Of Antibodies Against P. Ovale And P. Malariae Was Found In Asymptomatic Blood Donors. The Proportion Of Mixed Infections Involving Three Species Was Also Unexpected. These Data Suggest That Determining Seroprevalence For These Cryptic Species Is An Appropriate Tool To Estimate Their Incidence, At The Eve Of Upcoming Anti-P. Falciparum Vaccination Campaigns.


Assuntos
Anticorpos Antiprotozoários/sangue , Malária/epidemiologia , Plasmodium malariae/imunologia , Plasmodium ovale/imunologia , África Ocidental , Doadores de Sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Plasmodium falciparum/imunologia , Estudos Soroepidemiológicos
12.
Malar J ; 12: 279, 2013 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-23927596

RESUMO

BACKGROUND: Malaria is a leading cause of mortality in southern Benin. The main causative agent, Plasmodium falciparum, poses a threat on critical transfusions in pregnant women and children. This study's objective was to compare the performance of different malaria screening methods in blood donors in southern Benin, a malaria-endemic country. METHODS: Blood from 2,515 voluntary blood donors in Benin was collected over a period of 10 months in ethylenediaminetetraacetic acid (EDTA) tubes, which were then classified according to extraction time: long rainy season, short dry season, short rainy season, and long dry season. Microscopic examination was used to count parasites. Parasite density (PD) was expressed as the number of parasites per µL of blood. Pan Plasmodium pLDH detection was assessed by an ELISA-malaria antigen test. Using crude soluble P. falciparum antigens, an ELISA-malaria antibody test detected anti-Plasmodium antibodies. RESULTS: Among the 2,515 blood donors (2,025 males and 488 females) screened, the rate of asymptomatic Plasmodium carriage was 295/2,515 (11.72%, 95% CI: 10.5-13.1%). Males had a higher infection rate (12.4%) than did females (8.8%). Parasite density was very low: between seven and100 parasites per µL of blood was reported in 80% of donors with parasitaemia. Three Plasmodium species were diagnosed: P. falciparum in 280/295 patients (95.0%), Plasmodium malariae in 14/295 (5.0%), and Plasmodium ovale in 1/295 (0.34%). Malaria prevalence in donors was higher during the rainy seasons (13.7%) compared with the dry seasons (9.9%). The use of a highly sensitive assay enabled pan Plasmodium pLDH detection in 966/2,515 (38.4%, 95% CI: 36.5%-40.3%). Malaria antibody prevalence was 1,859/2,515 (73.9%, 95% CI: 72.16-75.6%). Donors' antigenaemia and antibody levels varied significantly (P <0.05) over the course of the four seasons. The highest antigenaemia rate 323/630 (51.3%), was observed during the short rainy season, while the highest antibody prevalence, 751/886 (84.7%), was recorded during the long dry season. CONCLUSION: Blood donations infected with Plasmodium can transmit malaria to donation recipients. Malaria diagnostic methods are currently available, but the feasibility criteria for mass screening in endemic areas become preponderant. Detection of the pLDH antigen seems to be an adequate screening tool in endemic areas, for this antigen indicates parasite presence. Routine screening of all donated blood would prevent infected blood donations and reduce P. falciparum transmission in critical patients, such as children and pregnant women. This tool would also decrease medical prophylaxis in donation recipients and contribute to lower Plasmodium resistance.


Assuntos
Antígenos de Protozoários/sangue , Doadores de Sangue , Sangue/parasitologia , Técnicas de Laboratório Clínico/métodos , L-Lactato Desidrogenase/sangue , Programas de Rastreamento/métodos , Plasmodium/enzimologia , Adolescente , Adulto , Idoso , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Benin , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , L-Lactato Desidrogenase/imunologia , Malária/diagnóstico , Masculino , Microscopia/métodos , Pessoa de Meia-Idade , Plasmodium/isolamento & purificação , Adulto Jovem
13.
Eur J Drug Metab Pharmacokinet ; 37(2): 125-32, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21811894

RESUMO

This study aimed at investigating the contribution of CYP2C9 and VKORC1 genetic polymorphisms to inter-individual variability of acenocoumarol pharmacokinetics and pharmacodynamics in Black Africans from Benin. Fifty-one healthy volunteers were genotyped for VKORC1 1173C>T polymorphism. All of the subjects had previously been genotyped for CYP2C9*5, CYP2C9*6, CYP2C9*8, CYP2C9*9 and CYP2C9*11 alleles. Thirty-six subjects were phenotyped with a single 8 mg oral dose of acenocoumarol by measuring plasma concentrations of (R)- and (S)-acenocoumarol 8 and 24 h after the administration using chiral liquid-chromatography tandem mass-spectrometry. International normalized ratio (INR) values were determined prior to and 24 h after the drug intake. The allele frequency of VKORC1 variant (1173C>T) was 1.96% (95% CI 0.0-4.65%). The INR values did not show statistically significant difference between the CYP2C9 genotypes, but were correlated with body mass index and age at 24 h post-dosing (P < 0.05). At 8 h post dose, the (S)-acenocoumarol concentrations in the CYP2C9*5/*8 and CYP2C9*9/*11 genotypes were about 1.9 and 5.1 fold higher compared with the CYP2C9*1/*1 genotype and 2.2- and 6.0-fold higher compared with the CYP2C9*1/*9 group, respectively. The results indicated that pharmacodynamic response to acenocoumarol is highly variable between the subjects. This variability seems to be associated with CYP2C9*5/*8 and *9/*11 variant and demographic factors (age and weight) in Beninese subjects. Significant association between plasma (S)-acenocoumarol concentration and CYP2C9 genotypes suggested the use of (S)-acenocoumarol for the phenotyping purpose. Larger number of subjects is needed to study the effect of VKORC1 1173C>T variant due to its low frequency in Beninese population.


Assuntos
Acenocumarol/farmacocinética , Anticoagulantes/farmacocinética , Hidrocarboneto de Aril Hidroxilases/genética , Oxigenases de Função Mista/genética , Acenocumarol/farmacologia , Adulto , Fatores Etários , Anticoagulantes/farmacologia , Benin , População Negra , Índice de Massa Corporal , Cromatografia Líquida/métodos , Citocromo P-450 CYP2C9 , Feminino , Genótipo , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Espectrometria de Massas em Tandem/métodos , Vitamina K Epóxido Redutases
14.
Planta Med ; 77(6): 641-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21240839

RESUMO

Buruli ulcer (BU), caused by Mycobacterium ulcerans, has recently been recognized by the World Health Organization (WHO) as an important emerging disease. It is largely a problem of the poor in remote rural areas and has emerged as an important cause of human suffering. While antimycobacterial therapy is often effective for the earliest nodular or ulcerative lesions, for advanced ulcerated lesions, surgery is sometimes necessary. Antimycobacterial drugs may also prevent relapses or disseminated infections. Efficient alternatives different from surgery are presently explored because this treatment deals with huge restrictive factors such as the necessity of prolonged hospitalization, its high cost, and the scars after surgery. Traditional treatment remains the first option for poor populations of remote areas who may have problems of accessibility to synthetic products because of their high cost. The search for efficient natural products active on M. ulcerans should then be encouraged because they are part of the natural heritage of these populations; they are affordable financially and can be used at the earliest stage. This review provides a number of tests that will help to evaluate the antimycobacterial activity of natural products against M. ulcerans, which are adapted to its slow growing rate, and lists active extracts published up to now in Medline.


Assuntos
Antibacterianos/farmacologia , Produtos Biológicos/farmacologia , Úlcera de Buruli/tratamento farmacológico , Testes de Sensibilidade Microbiana/métodos , Mycobacterium ulcerans/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bioensaio/métodos , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Úlcera de Buruli/microbiologia , Contagem de Colônia Microbiana , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Mycobacterium ulcerans/isolamento & purificação , Mycobacterium ulcerans/patogenicidade , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Radiometria/instrumentação , Radiometria/métodos
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