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1.
BMC Res Notes ; 17(1): 210, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39080672

RESUMO

BACKGROUND: The burden of chronic kidney disease (CKD) and kidney failure in Ghana is on the ascendency, with the prevalence of CKD estimated at 13.3%. Patients with CKD who progress to kidney failure require life sustaining kidney replacement therapy (KRT) which is almost exclusively available in Ghana as haemodialysis. Kidney transplantation is considered the best KRT option for patients with irreversible kidney failure due to its relative cost efficiency as well as its superiority in terms of survival and quality of life. However, because transplants may trigger an immune response with potential organ rejection, immunosuppressants such as tacrolimus dosing are required. OBJECTIVE: This study sought to determine single nucleotide polymorphisms in CYP3A5, CYP3A4 and MDR1 genes that affect the pharmacokinetics of Tacrolimus in a population of Ghanaian patients with kidney failure. METHOD: This cross-sectional study comprised of 82 kidney failure patients undergoing maintenance haemodialysis at the Renal and Dialysis unit of Korle-Bu Teaching Hospital (KBTH). Clinical and demographic data were collected and genomic DNA isolated. Samples were genotyped for specific SNPs using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Participants, 58/82 (70.73%) harbored the wildtype CYP3A5*1/*1 AA genotype, 20/82 (24.39%) carried the heterozygous CYP3A5*1/*3 AG genotype, and 4/82 (4.88%) had the homozygous mutant CYP3A5*3/*3 GG genotype. Also, 6/82 (7.32%) carried the wildtype AA genotype, 11/82 (13.41%) had the heterozygous AG genotype, and 65/82 (79.27%) harbored the homozygous mutant GG genotype of CYP3A4*1B (-290 A>G). For MDR1_Ex21 (2677 G>T), 81/82 (98.78%) carried the wildtype GG genotype, while 1/82 (1.22%) had the heterozygous GT genotype. For MDR1_Ex26 (3435 C>T), 63/82 (76.83%) had the wildtype CC genotype, while 18/82 (21.95%) carried the heterozygous CT genotype, and 1/82 (1.22%) harbored the mutant TT genotype. CONCLUSION: SNPs in CYP3A4, CYP3A5, and MDR1 genes in a population of Ghanaian kidney failure patients were described. The varying SNPs of the featured genes suggest the need to consider the genetic status of Ghanaians kidney failure patients prior to transplantation and tacrolimus therapy.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Citocromo P-450 CYP3A , Imunossupressores , Polimorfismo de Nucleotídeo Único , Tacrolimo , Centros de Atenção Terciária , Humanos , Polimorfismo de Nucleotídeo Único/genética , Gana/epidemiologia , Feminino , Masculino , Citocromo P-450 CYP3A/genética , Tacrolimo/farmacocinética , Tacrolimo/administração & dosagem , Pessoa de Meia-Idade , Adulto , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Imunossupressores/administração & dosagem , Estudos Transversais , Insuficiência Renal/genética , Idoso , Diálise Renal
2.
BMC Immunol ; 25(1): 14, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336647

RESUMO

BACKGROUND: Haemoglobin (Hb) variants such as sickle cell trait (SCT/HbAS) play a role in protecting against clinical malaria, but little is known about the development of immune responses against malaria parasite (Plasmodium falciparum surface protein 230 (Pfs230) and Plasmodium falciparum erythrocyte binding antigen 175 region-3 (PfEBA175-3R)) and vector (on the An. gambiae Salivary Gland Protein-6 peptide 1 (gSG6-P1)) antigens in individuals with variants Hb genotypes. This study assessed antibody (IgG) responses against malaria parasite, Pfs230 and PfEBA175-3R and vector, gSG6-P1 in febrile individuals with variant Hb genotypes. METHODS: The study was conducted on symptomatic malaria patients attending various healthcare facilities throughout Ghana. Microscopy and ELISA were used to determine the natural IgG antibody levels of gSG6-P1, PfEBA175-3R & Pfs230, and Capillarys 2 Flex Piercing was used for Hb variants determination. RESULTS: Of the 600 symptomatic malaria patients, 50.0% of the participants had malaria parasites by microscopy. The majority 79.0% (398/504) of the participants had Hb AA, followed by HbAS variant at 11.3% (57/504) and HbAC 6.7% (34/504). There were significantly (p < 0.0001) reduced levels of gSG6-P1 IgG in individuals with both HbAC and HbAS genotypes compared to the HbAA genotype. The levels of gSG6-P1 IgG were significantly (p < 0.0001) higher in HbAS compared to HbAC. Similarly, Pfs230 IgG and PfEBA-175-3R IgG distributions observed across the haemoglobin variants were significantly higher in HbAC relative to HbAS. CONCLUSION: The study has shown that haemoglobin variants significantly influence the pattern of anti-gSG6-P1, Pfs230, and PfEBA-175 IgG levels in malaria-endemic population. The HbAS genotype is suggested to confer protection against malaria infection. Reduced exposure to infection ultimately reduces the induction of antibodies targeted against P. falciparum antigens.


Assuntos
Antígenos de Grupos Sanguíneos , Malária Falciparum , Malária , Humanos , Gana/epidemiologia , Hemoglobinas/metabolismo , Malária Falciparum/epidemiologia , Plasmodium falciparum , Genótipo , Imunoglobulina G , Imunidade
3.
Ghana Med J ; 57(1): 19-27, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37576370

RESUMO

Objectives: This study determined the prevalence of hypertension and its associated factors among patients attending the HIV clinic at the Korle-Bu Teaching Hospital (KBTH). Design: A hospital-based cross-sectional study was conducted at KBTH. The prevalence of hypertension was estimated among study participants, and socio-demographic, lifestyle, anthropometric, metabolic and HIV/ART-related factors associated with hypertension were determined by logistic regression modelling. Setting: Study participants were recruited from the HIV clinic at the KBTH. Participants: A total of 311 Persons Living with HIV were recruited as study participants. Interventions: Simple random sampling technique was used to recruit study participants. A questionnaire adapted from the WHO STEPwise approach to chronic disease risk-factor surveillance was used to collect study participants' data. Results: The prevalence of hypertension was 36.7%, and the factors associated with hypertension were increasing age, positive family history of hypertension, minimal exercising, current BMI ≥25.0 kg/m2, total cholesterol level ≥5.17 mmol/L, exposure to anti-retroviral therapy (ART) and increasing duration of ART exposure. Conclusions: This study shows a high prevalence of hypertension among patients attending the HIV clinic at KBTH, associated with exposure to ART and increasing duration of this exposure. Blood pressure monitoring should move from routine to a more purposeful screening of patients for hypertension. Patients with the identified risk factors should be encouraged to have regular blood pressure measurements at home and not only when they visit the HIV clinic. Funding: Office of Research, Innovation and Development (ORID) of the University of Ghana. The funding agency was not involved in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.


Assuntos
Infecções por HIV , Hipertensão , Humanos , Estudos Transversais , Hospitais de Ensino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Fatores de Risco , Hipertensão/epidemiologia , Gana/epidemiologia , Prevalência
4.
Malar J ; 22(1): 58, 2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36803541

RESUMO

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria in Ghana. Artemisinin (ART) tolerance in Plasmodium falciparum has arisen in Southeast Asia and recently, in parts of East Africa. This is ascribed to the survival of ring-stage parasites post treatment. The present study sought to assess and characterize correlates of potential ART tolerance based on post-treatment parasite clearance, ex vivo and in vitro drug sensitivity, and molecular markers of drug resistance in P. falciparum isolates from children with uncomplicated malaria in Ghana. METHODS: Six months to fourteen years old children presenting with acute uncomplicated malaria (n = 115) were enrolled in two hospitals and a Health Centre in Ghana's Greater Accra region and treated with artemether-lumefantrine (AL) according to body weight. Pre- and post-treatment parasitaemia (day 0 and day 3) was confirmed by microscopy. The ex vivo ring-stage survival assay (RSA) was used to detect percent ring survival while the 72 h SYBR Green I assay was used to measure the 50% inhibition concentration (IC50s) of ART and its derivatives and partner drugs. Genetic markers of drug tolerance /resistance were evaluated using selective whole genome sequencing. RESULTS: Of the total of 115 participants, 85 were successfully followed up on day 3 post-treatment and 2/85 (2.4%) had parasitaemia. The IC50 values of ART, artesunate (AS), artemether (AM), dihydroartemisinin (DHA), amodiaquine (AQ), and lumefantrine (LUM) were not indicative of drug tolerance. However, 7/90 (7.8%) pre-treatment isolates had > 10% ring survival rates against DHA. Of the four isolates (2 RSA positive and 2 RSA negative) with high genomic coverage, P. falciparum (Pf) kelch 13 K188* and Pfcoronin V424I mutations were only present in the two RSA positive isolates with > 10% ring survival rates. CONCLUSIONS: The observed low proportion of participants with day-3 post-treatment parasitaemia is consistent with rapid ART clearance. However, the increased rates of survival observed in the ex vivo RSA against DHA, maybe a pointer of an early start of ART tolerance. Furthermore, the role of two novel mutations in PfK13 and Pfcoronin genes, harboured by the two RSA positive isolates that had high ring survival in the present study, remains to be elucidated.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Humanos , Criança , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Plasmodium falciparum/genética , Combinação Arteméter e Lumefantrina/uso terapêutico , Gana , Combinação de Medicamentos , Artemeter/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Lumefantrina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Tolerância a Medicamentos
5.
Ghana Med J ; 57(3): 257, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38957666
6.
Int J Gynaecol Obstet ; 149(2): 203-210, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32078159

RESUMO

OBJECTIVE: To determine the prevalence and key predictors of perinatal depression among women in Accra. METHOD: A two-step hospital-based cross-sectional study from May to July 2016. Patient Health Questionnaire version 9 was administered to postpartum mothers, and those aged 18 years or older with scores above 5 who delivered at LEKMA, Ridge, and Korle Bu Hospitals were recruited. A modified Edinburgh Postnatal Depression Scale was used to assess depression at 2 weeks postpartum. Associations between perinatal depression and sociodemographic/obstetric variables were assessed by χ2 and multivariate logistic regression. RESULTS: Among 1456 women screened, the prevalence of mental health disorders was 27.5% (400/1456). Of 350 women recruited, perinatal depression at 2 weeks postpartum was 8.6%, 31.6%, and 41.1% at LEKMA, Ridge, and Korle Bu, respectively. Mothers younger than 20 years and older than 35 years at Korle Bu had depression. Vaginal delivery increased the odds of perinatal depression at Ridge and Korle Bu. Blood transfusion was associated with depression at all three hospitals. CONCLUSION: Blood transfusion, but not other variables, was associated with perinatal depression at 2 weeks postpartum in Accra. Understanding the prevalence of perinatal depression and its associated risk factors in Ghana will aid policy decisions, planning, and clinical management.


Assuntos
Parto Obstétrico/efeitos adversos , Depressão Pós-Parto/epidemiologia , Depressão/epidemiologia , Adolescente , Adulto , Transfusão de Sangue/estatística & dados numéricos , Estudos de Casos e Controles , Estudos Transversais , Depressão/diagnóstico , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/etiologia , Feminino , Gana/epidemiologia , Humanos , Modelos Logísticos , Gravidez , Prevalência , Escalas de Graduação Psiquiátrica , Fatores de Risco
7.
J Neurovirol ; 25(4): 464-474, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31028691

RESUMO

Peripheral neuropathy (PN) is the most frequent neurological complication in people living with HIV/AIDS. Neurological damage was identified to not only be caused by the viral infection itself but also through neurotoxic antiretroviral therapy (ART). PN is associated with a variety of risk factors; however, detailed knowledge is scarce for sub-Saharan African populations, bearing among the highest HIV/AIDS infection burden.In a cross-sectional study, we assessed the prevalence of PN in 525 adult outpatients suffering from HIV/AIDS and admitted to the largest tertiary hospital in Ghana. Through a detailed questionnaire and clinical examination including neurologic assessment and laboratory blood sample testing, this study investigated associations of PN with demographic and health determinants and identified risk factors associated with sensory neuropathy.The prevalence of PN in the Ghanaian cohort was 17.7% and increased odd ratios (OR) when patients were taller (> 1.57 m; OR = 3.84; 95% CI 1.38-10.66) or reached the age > 34 years (p = 0.124). Respondents with longer education duration had significantly less PN (≥ 9 years of education; OR = 0.49; 95% CI 0.26-0.92). The study also identified significant association of PN to both waist and hip girth and neutrophil counts. Curiously, higher adjusted odd ratios (aOR) of PN of patients under ART treatment were observed when CD4 lymphocytes were elevated (aOR = 0.81; 95% CI 0.36-1.83 and aOR = 2.17; 95% CI 0.93-5.05, for 300 and 600 counts, respectively). For patients on ART, an increase of 10 CD4 cell count units increased their chance of developing PN by 1% (aOR = 1.01; 95% CI 1.00 to 1.03).Despite current drug application regulations, prevalence of PN is still unacceptably high in sub-Saharan African populations. Reduction in chronic morbidity through a health system with routine monitoring, early diagnosis and prompt intervention, and effective case management can improve people living with HIV/AIDS' quality of life.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Estudos Transversais , Feminino , Gana/epidemiologia , HIV/efeitos dos fármacos , HIV/enzimologia , HIV/crescimento & desenvolvimento , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Masculino , Razão de Chances , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/virologia , Prevalência , Qualidade de Vida/psicologia , Fatores de Risco , Inquéritos e Questionários , Centros de Atenção Terciária
8.
Diseases ; 6(4)2018 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-30274269

RESUMO

Endothelial nitric oxide synthase (eNOS) variants have been found to be associated with several vascular disorders as well as the pathogenesis of sickle cell disease (SCD) complications such as vaso-occlusive crises (VOC). Studies on eNOS gene variants among SCD patients are rare in Ghana and several other African countries. The current study aimed to determine a possible association between variants of the eNOS gene (variable number of tandem repeats in intron 4 and T786C) in SCD complications among Ghanaian patients. This was a cross-sectional study involving 89 HbSS patients with complications and 46 HbSS patients without complications. Genomic DNA was extracted from leukocytes in the buffy coat and separated from collected whole blood samples of the study participants. PCR amplification, followed by restriction fragment length polymorphism (RFLP) was used to genotype T786C (rs2070744) variants. Variable number of tandem repeats (VNTR) in intron 4 was genotyped by PCR and direct electrophoresis. There was a significant difference in the genotype frequency of the T786C variant between HbSS patients with complications and those without complications (p = 0.0165). However, there was no significant difference in the VNTR intron 4 variant of the eNOS gene between patients with complications and those without complications (p > 0.05). The study shows an association between the eNOS gene variant (T786C) and complications in SCD.

9.
Int J Gynaecol Obstet ; 141(1): 26-31, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29318600

RESUMO

OBJECTIVE: To examine factors influencing contraceptive use among women living with HIV/AIDS. METHODS: The present cross-sectional study included a randomly selected sample of sexually active females aged 15-60 years who were living with HIV/AIDS and receiving care at the HIV Clinic, Korle Bu Teaching Hospital, Accra, Ghana, between September 1 and November 31, 2016. Data were collected via a structured interviewer-administered questionnaire. RESULTS: Among 202 women who completed the survey, 50 (24.7%) were using contraceptives. Of the women using contraception, 39 (78%) were married and 6 (12%) were cohabiting. Twenty-eight (56%) reported that their primary sexual partners were HIV-positive, 14 (28%) had HIV-negative partners, and 8 (16%) did not know their partner's HIV status. Condoms were used by 42 (84%) women and the majority (41 [82%]) wanted to have more children; almost all (47 [94%]) had received counseling on contraceptive use. Overall, 133 (65.8%) and 45 (22.3%) women reported that they would prefer to share their family planning concerns with a doctor and nurse, respectively, at the HIV clinic. CONCLUSION: Women living with HIV/AIDS desired more children but preferred to share their family planning concerns with their clinician at the HIV clinic. Integrating HIV care and reproductive health services could help these women achieve childbearing goals safely.


Assuntos
Comportamento Contraceptivo/estatística & dados numéricos , Infecções por HIV/epidemiologia , Adolescente , Adulto , Preservativos/estatística & dados numéricos , Aconselhamento/estatística & dados numéricos , Estudos Transversais , Feminino , Gana/epidemiologia , Hospitais de Ensino , Humanos , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
10.
BMC Res Notes ; 9(1): 507, 2016 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-27938396

RESUMO

BACKGROUND: Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR. Influence of patient specific factors and gene variations within VKORC1, CYP2C9 and CYP4F2 were determined in patients on either high or low warfarin maintenance dose. RESULTS: One hundred and forty-one patients took part in the study with 79 (56%) participants being Female. The median age of the study participants was 48 years [IQR: 34-58]. The median duration for patients to be on warfarin therapy was 24 months [IQR: 10-72]. Majority of the study participants (80.9%, n = 114) did not have any side effects to warfarin. CYP2C9*2 and CYP2C9*3 variant alleles were not detected. VKORC1 variant allele was observed at 6% and CYP4F2 variant allele was observed at 41%. Duration of patients on warfarin therapy was marginally associated with high warfarin dose (adjusted OR = 1.01 [95% CI 1.00-1.02], p = 0.033) while the odds of heterozygous individuals (G/A) for VKORC1 gene to have high warfarin dose compared to persons with homozygous (G/G) (adjusted OR = 0.06 [95% CI 0.01-0.63], p = 0.019). Age, gender, diagnosis, presence of side effects and other medications were not associated with warfarin dose (p = 0.05). CONCLUSION: This study provides data on VKORC1 and CYP4F2 variants among an indigenous African population. Duration of patients on warfarin therapy was marginally associated with high warfarin dose. CYP2C9*2 and *3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians.


Assuntos
Anticoagulantes/uso terapêutico , Polimorfismo Genético , Varfarina/uso terapêutico , Adolescente , Adulto , Idoso , Alelos , Citocromo P-450 CYP2C9/genética , Família 4 do Citocromo P450/genética , Etnicidade , Feminino , Frequência do Gene , Genótipo , Gana , Heterozigoto , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Razão de Chances , Farmacogenética , Fatores de Risco , Classe Social , Vitamina K Epóxido Redutases/genética , Adulto Jovem
11.
Drug Saf ; 37(6): 433-48, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24788801

RESUMO

BACKGROUND: Antimalarial treatment strategies have changed much in the last 15 years, resulting in an increased variety of medicines available. Active pharmacovigilance methods are important for continued safety surveillance of these medicines, particularly in environments in which there is variability in treatments prescribed and limited confirmatory diagnostic capacity as well as limited ability of spontaneous reporting pharmacovigilance systems to generate much needed safety information quickly and efficiently. OBJECTIVE: Our objective was to use the cohort-event monitoring (CEM) technique to gather drug utilization and adverse event data for patients prescribed antimalarial medicines in an outpatient setting. METHODS: The characteristics of a large urban African cohort of outpatients (n = 2,831) receiving antimalarial medications are described. The cohort was actively surveyed over the subsequent week to record adverse events, using follow-up phone calls, paper reports, and/or voluntary return clinic visits. Adverse events reported in the cohort were analysed overall and by clinically relevant age and medication groupings. RESULTS: At least one event was reported in 29.4 % of patients. Adverse events were more likely to be reported in subjects older than 12 years of age, and by patients prescribed an artesunate-amodiaquine combination. A range of adverse events were reported, the most frequent higher level terms being asthenic conditions (10.1 % of total cohort), neurological signs and symptoms (4.5 %), headaches (3.1 %), appetite disorders (2.1 %), and disturbances in consciousness (1.6 %). There were three reports of possible extrapyramidal events (two cases of tremor "hand and back shaking all over" and one case of tongue protrusion), which may appear to be related to combinations including amodiaquine and an artemisinin. CONCLUSION: The CEM methodology is a useful tool for monitoring the safety of widely available and utilized medicines, particularly in an urban environment where spontaneous reporting yields poor results and where the availability of various regimens and high levels of medicine usage can give valuable 'real-life' safety data. The types and frequencies of events reported reflected the types of events expected in patients prescribed antimalarials and nearly all events reported are listed in the summary of product characteristics of the medicines involved.


Assuntos
Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Malária/tratamento farmacológico , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Criança , Pré-Escolar , Monitoramento de Medicamentos/métodos , Uso de Medicamentos/estatística & dados numéricos , Feminino , Gana , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos Prospectivos , Adulto Jovem
12.
BMC Complement Altern Med ; 12: 65, 2012 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-22607580

RESUMO

BACKGROUND: Cassia sieberiana is a savannah tree with a wide phytotherapeutic application including the use of its roots in the management of various stomach disorders including gastric ulcer, stomach pains and indigestion. The aim of the study is to evaluate the antioxidant, gastric cytoprotective prostaglandins, secretory phospholipase A2, phytochemical and acute toxicity properties of Cassia sieberiana roots bark extract in a bid to justify its phytotherapeutic applications in gastric ulcer. METHODS: Antioxidant and radical scavenging activities of the roots bark extract of Cassia sieberiana were assayed. Serum secretory phospholipase A2 (sPLA2) concentration and activity and the formation of gastric mucosal prostaglandins E2 (PGE2) and I2 (PGI2) were also assessed. Comparisons between means were performed using analysis of variance (ANOVA) followed by Students Standard Newman-Keuls post hoc analysis to determine statistical significance. P < 0.05 was considered significant. RESULTS: The extract was found to possess significant ferric reducing antioxidant power and can scavenge hydroxyl radicals. The extract also possesses DPPH scavenging activity, can chelate ferrous ion and a dose-dependent protective effect against lipid peroxidation and free radical generation. Prostaglandin studies showed that the roots bark extract dose dependently increased gastric mucosal PGE2 and PGI2 levels and also decreased serum sPLA2 activity. Phytochemical analyses suggest that the roots extract contains polyhydroxyl/phenolic substances. Acute toxicity test showed no sign of toxicity up to a dose level of 2000 mg/kg body weight p.o. CONCLUSIONS: C. sieberiana roots extract possesses significant antioxidant and gastric cytoprotective prostaglandin properties as well as serum secretory phospholipase A2 inhibitory activity which could be due to its content of polyhydroxy and/or phenolic substances. This may justify its use as an anti-ulcerogenic agent in traditional medicine in West Africa.


Assuntos
Antioxidantes/administração & dosagem , Cassia/química , Citoproteção/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Raízes de Plantas/química , Prostaglandinas/metabolismo , Úlcera Gástrica/tratamento farmacológico , Animais , Antioxidantes/química , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Cobaias , Humanos , Masculino , Fosfolipases A2 Secretórias/sangue , Casca de Planta/química , Extratos Vegetais/química , Ratos , Ratos Endogâmicos F344 , Úlcera Gástrica/metabolismo
13.
Pharmacogenomics ; 12(6): 897-905, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21692619

RESUMO

The WHO embraces evidence-based medicine to formulate an essential medicines list (EML) considering disease prevalence, drug efficacy, drug safety and cost-effectiveness. The EML is used by developing countries to build a national formulary. As pharmacogenetics in developed countries evolves, the Pharmacogenetics for Every Nation Initiative (PGENI) convened with representatives from China, Mexico, Ghana and South Africa in August 2009 to evaluate the use of human pharmacogenetics to enhance global drug use policy. The diseases causing mortality, the lack of integration of pharmacovigilance at the national formulary level, the pharmacogenetics research agenda and pharmacogenetics clinician education did not differ greatly among the countries. While there are many unanswered questions, systematically incorporating pharmacogenetics at the national formulary level promises to improve global drug use.


Assuntos
Tratamento Farmacológico/normas , Política de Saúde , Farmacogenética/normas , Análise Custo-Benefício/normas , Países em Desenvolvimento , Medicina Baseada em Evidências , Humanos , Grupos Populacionais , Organização Mundial da Saúde
14.
BMC Med Genet ; 11: 111, 2010 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-20630055

RESUMO

BACKGROUND: Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies. METHODS: Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients. RESULTS: We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). CYP3A4*1B, CYP3A5*3 and CYP3A5*6 alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. CYP3A5*1/CYP3A5*1 and CYP3A5*1/CYP3A5*3 genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin. CONCLUSION: A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antiparasitários/metabolismo , Citocromo P-450 CYP3A/genética , Ivermectina/metabolismo , Polimorfismo Genético , Subfamília B de Transportador de Cassetes de Ligação de ATP , DNA/sangue , DNA/genética , DNA/isolamento & purificação , Resistência a Múltiplos Medicamentos/genética , Frequência do Gene , Genótipo , Gana , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
15.
BMC Med Genet ; 10: 124, 2009 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-19954515

RESUMO

BACKGROUND: Genetic influences on drug efficacy and tolerability are now widely known. Pharmacogenetics has thus become an expanding field with great potential for improving drug efficacy and reducing toxicity. Many pharmacologically-relevant polymorphisms do show variability among different populations. Knowledge of allelic frequency distribution within specified populations can be useful in explaining therapeutic failures, identifying potential risk groups for adverse drug reactions (ADRs) and optimising doses for therapeutic efficacy. We sought to determine the prevalence of clinically relevant Cytochrome P450 (CYP) 2C8, CYP2C9, and CYP2C19 variants in Ghanaians. We compared the data with other ethnic groups and further investigated intra country differences within the Ghanaian population to determine its value to pharmacogenetics studies. METHODS: RFLP assays were used to genotype CYP2C8 (*2, *3, *4) variant alleles in 204 unrelated Ghanaians. CYP2C9*2 and CYP2C19 (*2 and *3) variants were determined by single-tube tetra-primer assays while CYP2C9 (*3, *4, *5 and *11) variants were assessed by direct sequencing. RESULTS: Allelic frequencies were obtained for CYP2C8*2 (17%), CYP2C8*3 (0%), CYP2C8*4 (0%), CYP2C9*2 (0%), CYP2C9*3 (0%), CYP2C9*4 (0%), CYP2C9*5 (0%), CYP2C9*11 (2%), CYP2C19*2 (6%) and CYP2C19*3 (0%). CONCLUSION: Allele frequency distributions for CYP2C8, CYP2C9 and CYP2C19 among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations. Variant allele frequencies for CYP2C9 and CYP2C19 are reported for the first time among indigenous Ghanaian population.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , População Negra/genética , Polimorfismo Genético , Alelos , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP2C9 , Feminino , Frequência do Gene , Genótipo , Gana , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Fragmento de Restrição
16.
Jpn J Infect Dis ; 56(4): 165-7, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14583641

RESUMO

Several infectious diseases have been found to be associated with transfusion of blood and blood components. Reports from studies conducted in many African countries indicate a high incidence of blood-borne pathogens such as syphilis infections among healthy blood donors. The prevalence of syphilis antibodies in blood donors in Ghana is not known. This study was therefore conducted in order to determine the prevalence of antibodies to syphilis among blood donors seen between the months of January and March 2003 at the National Blood Transfusion Service, Accra area (Blood Bank) at the Korle-Bu Teaching Hospital, Accra, Ghana. The presence of antibodies specific for syphilis was tested using Venereal Disease Research Laboratory and particle agglutination test kit. A sero-prevalence rate of 7.5% was found. Our sample of blood donors was largely comprised of male subjects (500 out of 536 donors, and only 1 out of the 36 screened female donors was positive), making sex comparisons statistically undesirable. In both sexes, the age distribution of subjects positive for syphilis antibodies was from 19 - 54 (median age, 32) years. In conclusion, our results indicate that syphilis is prevalent among healthy blood donors in Ghana, and that there is a need to introduce the screening of donated blood for syphilis in Ghana.


Assuntos
Anticorpos Antibacterianos/sangue , Doadores de Sangue , Sífilis/epidemiologia , Adulto , Feminino , Gana/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos
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