Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Rep ; 11(1): 13945, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230563

RESUMO

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.


Assuntos
Disbiose/microbiologia , Disbiose/virologia , Gastroenterite/microbiologia , Gastroenterite/virologia , Microbioma Gastrointestinal , Adolescente , Adulto , Bactérias/classificação , Biodiversidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Diarreia/microbiologia , Diarreia/virologia , Fezes/microbiologia , Feminino , Gana , Humanos , Masculino , Filogenia , Rotavirus/fisiologia
2.
Front Cell Infect Microbiol ; 11: 646467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084754

RESUMO

HIV-1 infected individuals under antiretroviral therapy can control viremia but often develop non-AIDS diseases such as cardiovascular and metabolic disorders. Gut microbiome dysbiosis has been indicated to be associated with progression of these diseases. Analyses of gut/fecal microbiome in individual regions are important for our understanding of pathogenesis in HIV-1 infections. However, data on gut/fecal microbiome has not yet been accumulated in West Africa. In the present study, we examined fecal microbiome compositions in HIV-1 infected adults in Ghana, where approximately two-thirds of infected adults are females. In a cross-sectional case-control study, age- and gender-matched HIV-1 infected adults (HIV+; n = 55) and seronegative controls (HIV-; n = 55) were enrolled. Alpha diversity of fecal microbiome in HIV+ was significantly reduced compared to HIV- and associated with CD4 counts. HIV+ showed reduction in varieties of bacteria including Faecalibacterium, the most abundant in seronegative controls, but enrichment of Proteobacteria. Ghanaian HIV+ exhibited enrichment of Dorea and Blautia; bacteria groups whose depletion has been reported in HIV-1 infected individuals in several other cohorts. Furthermore, HIV+ in our cohort exhibited a depletion of Prevotella, a genus whose enrichment has recently been shown in men having sex with men (MSM) regardless of HIV-1 status. The present study revealed the characteristics of dysbiotic fecal microbiome in HIV-1 infected adults in Ghana, a representative of West African populations.


Assuntos
Infecções por HIV , HIV-1 , Microbiota , Adulto , Estudos de Casos e Controles , Estudos Transversais , Disbiose , Feminino , Gana , Humanos , Masculino
3.
Jpn J Infect Dis ; 74(1): 42-47, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32611986

RESUMO

Recent studies have indicated an association between gut microbiome composition and various disorders, including infectious diseases. The composition of the microbiome differs among ethnicities and countries, possibly resulting in diversified interactions between host immunity and the gut microbiome. Characterization of baseline microbiome composition in healthy people is an essential step for better understanding of the biological interactions associated with individual populations. However, data on the gut/fecal microbiome have not been accumulated for individuals in West Africa. In the present study, we examined the fecal microbiome composition in healthy adults in Ghana. Toward this, 16S rRNA gene libraries were prepared using bacterial fractions derived from 55 Ghanaian adults, which were then subjected to next-generation sequencing. The fecal microbiome of the Ghanaian adults was dominated by Firmicutes (Faecalibacterium, Subdoligranulum, and Ruminococcaceae UCG-014), Proteobacteria (Escherichia-Shigella and Klebsiella), and Bacteroidetes (Prevotella 9 and Bacteroides), consistent with previous observations in African cohorts. Further, our analysis revealed differences in microbiome composition and a lower diversity of the fecal microbiome in the Ghanaian cohort compared with those reported in non-African countries. This is the first study to describe substantial fecal microbiome data obtained using high-throughput metagenomic tools on samples derived from a cohort in Ghana. The data may provide a valuable basis for determining the association between the fecal microbiome and progression of various diseases in West African populations.


Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal/genética , Adulto , Bacteroidetes/genética , Estudos Transversais , Feminino , Firmicutes/genética , Gana , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Metagenômica , Microbiota , Pessoa de Meia-Idade , Proteobactérias/genética , RNA Bacteriano/isolamento & purificação , RNA Ribossômico 16S/genética
4.
Virol J ; 17(1): 114, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709248

RESUMO

BACKGROUND: Detection of HIV-1 transmitted drug resistance (TDR) and subtype diversity (SD) are public health strategies to assess current HIV-1 regimen and ensure effective therapeutic outcomes of antiretroviral therapy (ART) among HIV-1 patients. Globally, limited data exist on TDR and SD among blood donors. In this study, drug resistance mutations (DRMs) and SD amongst HIV-1 sero-positive blood donors in Accra, Ghana were characterized. METHODS: Purposive sampling method was used to collect 81 HIV sero-positive blood samples from the Southern Area Blood Center and confirmed by INNO-LIA as HIV-1 and/or HIV-2. Viral RNA was only extracted from plasma samples confirmed as HIV-1 positive. Complementary DNA (cDNA) was synthesized using the RNA as a template and subsequently amplified by nested PCR with specific primers. The expected products were verified, purified and sequenced. Neighbour-joining tree with the Kimura's 2-parameter distances was generated with the RT sequences using Molecular Evolutionary Genetic Analysis version 6.0 (MEGA 6.0). RESULTS: Out of the 81 plasma samples, 60 (74%) were confirmed as HIV-1 sero-positive by INNO-LIA HIVI/II Score kit with no HIV-2 and dual HIV-1/2 infections. The remaining samples, 21 (26%) were confirmed as HIV sero-negative. Of the 60 confirmed positive samples, (32) 53% and (28) 47% were successfully amplified in the RT and PR genes respectively. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. HIV-1 Subtypes including subtypes A, B, CRF02_AG and CRF09_cpx were found. CONCLUSION: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. CRF02_AG was most predominant, the recorded percentage of subtype B and the evolutionary relationship inferred by phylogenetic analysis may suggest possible subtype importation. However, a more prospective and detailed analysis is needed to establish this phenomenon. The data obtained would inform the selection of drugs for ART initiation to maximize therapeutic options in drug-naïve HIV-1 patients in Ghana.


Assuntos
Doadores de Sangue , Farmacorresistência Viral/genética , HIV-1/genética , Mutação , Filogenia , Adulto , Fármacos Anti-HIV/farmacologia , Doadores de Sangue/estatística & dados numéricos , Estudos Transversais , Feminino , Gana , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Adulto Jovem
5.
Infect Disord Drug Targets ; 20(2): 175-181, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30324895

RESUMO

BACKGROUND: Tumor necrosis factor and its receptors (sTNFR1 and sTNFR2) have been implicated in many infectious diseases. Identification of the key receptor (sTNFR1 or sTNFR2) which drives the immunopathogenesis of HIV infection is crucial in developing adjunctive therapy for HIV. OBJECTIVE: This study determined the expression levels of sTNFR1 and sTNFR2 in antiretroviral therapy (ART) - experienced and naïve HIV patients. METHODS: A total of 40 HIV patients comprising 30 with ART and 10 without ART were enrolled from the Pantang Hospital located in the Greater Accra Region of Ghana for data and blood collection. Serum concentrations of sTNFR1 and sTNFR2 were determined by ELISA. Mann- Whitney U test was used to examine differences in serum levels of sTNFR1 and sTNFR2 between patients on ART and ART naïve patients. Wilcoxon Signed-Rank test was performed to determine the difference between sTNFR1 and sTNFR2, and Kruskal Wallis test was conducted to compare the effect of different antiretroviral drugs on the levels of sTNFR1 and sTNFR2. P< 0.05 was considered statistically significant. RESULTS: A Wilcoxon Signed-Ranks Test indicated serum levels of sTNFR2 was statistically significantly higher than sTNFR1 (Z=-5.51; p<0.001). Levels of sTNFR1 and sTNFR2 did not differ by ART status U =91.00 (Z = -1.84), p = 0.065 and U = 131.50 (Z = -0.58, p =0.560), respectively. There were not significant differences in levels of TNFR2 H(2) = 1.86, p=0.395 and sTNFR1 (H (2) = 4.37, p=0.113 across different ART combinations. CONCLUSION: Compared to sTNFR1, the level of sTNFR2 is significantly increased during HIV infection irrespective of ART status. The high sTNFR2 level is not associated with antiretroviral drugs and may be another potential target for therapeutic development. This is the first study of sTNFRs in African population.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Adulto , Estudos Transversais , Feminino , Gana , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Solubilidade
6.
PLoS One ; 14(7): e0220181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31339937

RESUMO

Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with high oxidative stress in HIV patients. The disparity in antioxidant-oxidant levels in HIV patients favours viral replication and disease progression. This study aimed at determining the effect of ART on antioxidant enzymes activities and trace elements levels in Ghanaian HIV patients. A total of 242 participants; comprising of 105 HIV-infected patients on ART, 77 HIV-infected ART-naïve, and 60 HIV seronegative controls were recruited for the study. Whole blood was collected and used for haematological profiling, and the determination of CD4+ counts, superoxide dismutase (SOD) activity and trace element levels. Serum was used for liver function tests and the determination of glutathione reductase (GR) activity, and plasma was used to estimate reduced glutathione (GSH) levels. Low levels of haemoglobin (HB), hematocrit, mean cell volume (MCV) and mean cell hemoglobin (MCH), and trace elements were found in ART-naïve patients compared to those on ART and the seronegative controls. In the ART-naïve patients, glutathione reductase (GR) activity and reduced glutathione (GSH) level were significantly low compared to patients on ART and seronegative controls. Activity of SOD was significantly reduced in ART-naïve patients compared to those on ART and the control group, and manganese is the only trace element that showed a strong negative correlation with SOD activity and a positive and significant correlation with CD4+ count, and therefore needs to be investigated further. The study suggests that assessing antioxidant levels or enzymes activities of patients infected with HIV should be considered during therapy.


Assuntos
Antioxidantes/metabolismo , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Infecções por HIV/sangue , Superóxido Dismutase/sangue , Oligoelementos/sangue , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Gana/epidemiologia , Glutationa/sangue , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Superóxido Dismutase/metabolismo
7.
Virol J ; 15(1): 143, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223845

RESUMO

BACKGROUND: Antiretrovirals have been available in Ghana since 2003 for HIV-1 positive pregnant women for prevention of mother-to-child transmission (PMTCT). Suboptimal responses to treatment observed post-PMTCT interventions necessitated the need to investigate the profile of viral mutations generated. This study investigated HIV-1 drug resistance profiles in mothers in selected centres in Ghana on treatment with a history of prophylaxis. METHODS: Genotypic Drug Resistance Testing for HIV-1 was carried out. Subtyping was done by phylogenetic analysis and Stanford HIV Database programme was used for drug resistance analysis and interpretation. To compare the significance between the different groups and the emergence of drug resistance mutations, p values were used. RESULTS: Participants who had prophylaxis before treatment, those who had treatment without prophylaxis and those yet to initiate PMTCT showed 32% (8), 5% (3) and 15% (4) HIV-1 drug resistance associated mutations respectively. The differences were significant with p value < 0.05. Resistance Associated Mutations (RAMs) were seen in 14 participants (35%) to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The most common NRTI mutation found was M184 V; K103 N and A98G were the most common NNRTI mutations seen. Thymidine Analogue Mutations (TAMs) such as M41 L, K70R and T215Y were found in all the groups; the most common of the TAMs found were M41 L and T215Y. Majority of the subtypes were CRF02_AG (82%). CONCLUSION: In Ghana initiation of uninterrupted treatment upon diagnosis, coupled with drug resistance testing, would produce a better treatment outcome for HIV-1 positive pregnant women.


Assuntos
Fármacos Anti-HIV/farmacologia , Quimioprevenção/estatística & dados numéricos , Farmacorresistência Viral , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mutação de Sentido Incorreto , Fármacos Anti-HIV/administração & dosagem , Feminino , Genótipo , Gana , Infecções por HIV/prevenção & controle , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Mães , Filogenia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Análise de Sequência de DNA , Resultado do Tratamento
8.
PLoS One ; 13(5): e0195954, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29795558

RESUMO

Glutathione S-transferase (GST) family of enzymes are involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogens and xenobiotics. The GST enzymes play important roles in oxidative stress pathways, and polymorphisms in the GSTM1 and GSTT1 genes mediate susceptibility and outcome in different diseases. Human immunodeficiency virus (HIV) infection is associated with oxidative stress, but there is limited data on the frequency of deleted GSTM1 and GSTT1 genes in HIV/AIDS patients and their effect on progression among Ghanaians. This study sought to investigate the association between homozygous deletion of GSTM1 and GSTT1 genes (both null deletion) with HIV/AIDS disease progression in Ghanaian patients. HIV-infected individuals on antiretroviral therapy (ART), ART-naïve HIV patients, and HIV seronegative individuals were recruited for the study. HIV/AIDS disease progression was assessed by measuring CD4+ cell count and viral load of the patients, and GST polymorphism was determined by amplifying the GSTT1 and GSTM1 genes using multiplex PCR, with CYP1A1 gene as an internal control. The mean CD4+ count of patients that were naïve to ART (298 ± 243 cells/mm3) was significantly lower than that of patients on ART (604 ± 294 cells/mm3), and viral load was significantly lower in the ART-experienced group (30379 ± 15073 copies/mm3) compared to the ART-naïve group (209882 ± 75045 copies/mm3). Frequencies of GSTM1 and GSTT1 deletions were shown to be 21.9% and 19.8%, respectively, in the HIV patients, and patients with homozygous deletion of both GSTM1 and GSTT1 were more likely to have their CD4+ count rising above 350 cells/mm3 (OR = 6.44, 95% CI = 0.81-51.49, p = 0.039) suggesting that patients with homozygous deletion of GSTM1 and GSTT1 genes have slower disease progression. The findings of this study show that double deletion of glutathione S-transferases M1 and T1 is statistically associated with normal CD4+ count in patients diagnosed with HIV/AIDS. Further study is required to investigate the clinical importance of the both null deletion in HIV patients.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Glutationa Transferase/genética , Infecções por HIV/imunologia , HIV/imunologia , Homozigoto , Deleção de Sequência , Adulto , Estudos Transversais , Progressão da Doença , Feminino , Predisposição Genética para Doença , Genótipo , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco
9.
BMC Ophthalmol ; 16: 134, 2016 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-27487853

RESUMO

BACKGROUND: Patients infected with human immunodeficiency virus (HIV) usually develop some form of ocular complication in the different segments of the eye due to immune deficiency. In Ghana, data regarding ocular complications among HIV/AIDS patients is scarce. This study investigated the occurrence of ocular complications in HIV infected patients undergoing antiretroviral therapy at the Agogo Presbyterian Hospital in the Ashanti Region of Ghana. METHODS: Blood samples were taken from 100 confirmed HIV infected patients. The CD4 + T cell count and WHO clinical staging were determined. The patients were taken through thorough ophthalmic assessments to determine any ocular complications. RESULTS: Forty-eight patients (48 %) had at least one HIV-related ocular complication. These complications occurred more frequently among those with CD4 counts below 200 cells/µL. Of the participants with HIV-related ocular complications, 11 (23 %) had retinal microvasculopathy, 10 (21 %) showed allergic conjunctivitis, 7 (15 %) had HIV retinopathy and 7 (15 %) had conjunctival carcinoma. All the participants in the study were on first-line antiretroviral therapy; 68 % were females and 72 % were in the Stage 3 of the WHO Clinical Staging of HIV infection. CONCLUSION: The prevalence of ocular complications in HIV positive persons under treatment in Ghana is high. Lower CD4 + T cell counts coupled with age were predisposing factors to HIV-related ocular complications.


Assuntos
Terapia Antirretroviral de Alta Atividade , Oftalmopatias/epidemiologia , Infecções por HIV/complicações , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Oftalmopatias/etiologia , Feminino , Gana/epidemiologia , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Acuidade Visual , Adulto Jovem
10.
Ann Clin Microbiol Antimicrob ; 15: 29, 2016 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-27145868

RESUMO

BACKGROUND: Antibiotic resistance due to the presence of extended-spectrum beta-lactamases (ESBLs) among Enterobacteriaceae is a worldwide problem. Data from Ghana regarding this resistance mechanism is limited. This study was designed to investigate the presence of TEM-type ESBL genes, their locations and their conjugabilities in clinical isolates of enterobacteria collected from the Korle-Bu Teaching Hospital in Ghana. METHODS: Study isolates were characterized with respect to ESBL phenotype, TEM-type ESBL gene detection, location of the ESBL gene(s) and conjugability of the ESBL phenotype using nalidixic acid-resistant Escherichia coli K-12 as recipient. Phenotyping was by Kirby Bauer disk diffusion using cefpodoxime, ceftazidime, cefotaxime and their combinations with clavulanate. Gene detections were by PCR using blaTEM primers. RESULTS: Overall, 37.96 % of 137 clinical isolates showed ESBL phenotype. The ESBLs occurred mostly in Klebsiella spp. (42.3 %) and then Escherichia coli (34.6 %). The TEM gene was detected in 48.1 % of ESBL-positive isolates and was determined to be plasmid-borne in 24 of 25 blaTEM detections. Overall, 62.7 % of TEM-producing isolates transferred the ESBL phenotype by conjugation. CONCLUSIONS: The results highlight the presence of TEM-type ESBLs in the Korle-Bu Teaching Hospital and show considerable risk of environmental contamination through the urine of infected persons. An inhibition zone chart was generated which indicates the possible presence of complex beta-lactamase types. The data points to the fact that the ESBL-producing bacteria may disseminate this resistance mechanism via conjugation.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Gana , Humanos , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária/estatística & dados numéricos , beta-Lactamases/genética
11.
J Acquir Immune Defic Syndr ; 48(5): 599-606, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18645511

RESUMO

BACKGROUND: In Ghana, programs to expand antiretroviral access are being implemented. In this context, the dynamic genetic evolution of HIV-1 requires continuous surveillance, particularly when diverse genetic forms co-circulate. METHODS: Phylogenetic and antiretroviral resistance analyses of HIV-1 partial pol sequences from plasma RNA samples from 207 Ghanaian individuals were performed. RESULTS: 66% of infections were CRF02_AG, whereas 25% were unique recombinant forms (URFs). All 52 URFs were characterized by bootscanning. CRF02_AG was parental strain in 87% of URFs, forming recombinants with genetic forms circulating in minor proportions: CRF06_cpx, sub-subtype A3, CRF09_cpx and subtypes G and D. Two triple recombinants (CRF02_AG/A3/CRF06_cpx and CRF02_AG/A3/CRF09_cpx) were identified. Antiretroviral resistance analyses revealed that six individuals, five of which were antiretroviral drug-experienced, harbored mutations conferring high level of resistance to reverse transcriptase inhibitors. No major resistance mutations were identified in the protease, although insertions of one and three amino acids were detected. CONCLUSIONS: The high frequency of URFs detected probably reflects a significant incidence of coinfections or superinfections with diverse viral strains, which increases the genetic complexity of the HIV-1 epidemic in West Africa. Monitoring of HIV-1 drug resistance might provide data on the implications of intersubtype recombination in response to antiretrovirals.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/epidemiologia , HIV-1/genética , Mutação , Recombinação Genética , Genes pol , Gana/epidemiologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-1/classificação , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Polimorfismo Genético , Prevalência , Inibidores da Transcriptase Reversa/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...