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OBJECTIVE: The objective of this study was to evaluate cytogenetic changes in individuals submitted to oral human immunodeficiency virus pre-exposure prophylaxis use through the micronucleus test in oral mucosa. METHODS: This study consisted of 37 individuals, of whom 17 comprised the pre-exposure prophylaxis group and 20 comprised the control group. A total of 2,000 cells per slide were analyzed for the determination of micronuclei, binucleation, nuclear buds, and cytotoxicity parameters: pyknosis, karyolysis, and karyorrhexis (KR), in a double-blind manner. The repair index was also evaluated in this setting. RESULTS: In the mutagenicity parameters, the pre-exposure prophylaxis group showed increased frequencies of micronuclei (p=0.0001), binucleation (p=0.001), and nuclear buds (p=0.07). Regarding the cytotoxicity parameters, there was an increase with a statistical difference (p≤0.05) in the karyorrhexis frequency (p=0.001). Additionally, the repair system efficiency decreased in the pre-exposure prophylaxis group. CONCLUSION: These results indicate that individuals undergoing pre-exposure prophylaxis use have geno- and cytotoxicity in oral mucosal cells.
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Micronúcleos com Defeito Cromossômico , Profilaxia Pré-Exposição , Humanos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , HIV , Mucosa Bucal , Análise Citogenética , Dano ao DNARESUMO
OBJECTIVE: The objective of this study was to evaluate possible cytogenetic changes in children and adolescents with human immunodeficiency virus on antiretroviral therapy, through the micronucleus test in oral mucosa. METHODS: This was a prospective study consisted of 40 individuals, of whom 21 comprised the human immunodeficiency virus group and 19 comprised the control group. Children and adolescents with human immunodeficiency virus were enrolled. The inclusion criteria were <18 years old and consent in participating in the study. The exclusion criteria were the presence of numerous systemic comorbidities, oral lesions, the habit of smoking, alcohol consumption, and X-rays or CT scans taken within 15 days prior to sample collection. A gentle scraping was performed on the inner portion of the jugal mucosa on both sides. A total of 2,000 cells per slide were analyzed for the determination of mutagenicity parameters as follows: micronuclei, binucleation, and nuclear buds. For measuring cytotoxicity, the following metanuclear changes were evaluated: pyknosis, karyolysis, and karyorrhexis, in a double-blind manner. The repair index was also evaluated in this setting. RESULTS: The human immunodeficiency virus group showed high frequencies of micronuclei (p=0.05), binucleated cells (p=0.001), and nuclear buds (p=0.03). In the cytotoxicity parameters, represented by the cell death phases, there was an increase with statistical difference (p≤0.05) in the karyorrhexis frequency (p=0.05). Additionally, repair index was decreased in the human immunodeficiency virus group. CONCLUSION: These results indicate that human immunodeficiency virus -infected individuals undergoing antiretroviral therapy have cytogenetic changes in oral mucosal cells.
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Infecções por HIV , HIV , Adolescente , Criança , Humanos , Mucosa Bucal , Estudos Prospectivos , Antirretrovirais , Infecções por HIV/tratamento farmacológico , Análise CitogenéticaRESUMO
SUMMARY OBJECTIVE: The objective of this study was to evaluate cytogenetic changes in individuals submitted to oral human immunodeficiency virus pre-exposure prophylaxis use through the micronucleus test in oral mucosa. METHODS: This study consisted of 37 individuals, of whom 17 comprised the pre-exposure prophylaxis group and 20 comprised the control group. A total of 2,000 cells per slide were analyzed for the determination of micronuclei, binucleation, nuclear buds, and cytotoxicity parameters: pyknosis, karyolysis, and karyorrhexis (KR), in a double-blind manner. The repair index was also evaluated in this setting. RESULTS: In the mutagenicity parameters, the pre-exposure prophylaxis group showed increased frequencies of micronuclei (p=0.0001), binucleation (p=0.001), and nuclear buds (p=0.07). Regarding the cytotoxicity parameters, there was an increase with a statistical difference (p≤0.05) in the karyorrhexis frequency (p=0.001). Additionally, the repair system efficiency decreased in the pre-exposure prophylaxis group. CONCLUSION: These results indicate that individuals undergoing pre-exposure prophylaxis use have geno- and cytotoxicity in oral mucosal cells.
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SUMMARY OBJECTIVE: The objective of this study was to evaluate possible cytogenetic changes in children and adolescents with human immunodeficiency virus on antiretroviral therapy, through the micronucleus test in oral mucosa. METHODS: This was a prospective study consisted of 40 individuals, of whom 21 comprised the human immunodeficiency virus group and 19 comprised the control group. Children and adolescents with human immunodeficiency virus were enrolled. The inclusion criteria were <18 years old and consent in participating in the study. The exclusion criteria were the presence of numerous systemic comorbidities, oral lesions, the habit of smoking, alcohol consumption, and X-rays or CT scans taken within 15 days prior to sample collection. A gentle scraping was performed on the inner portion of the jugal mucosa on both sides. A total of 2,000 cells per slide were analyzed for the determination of mutagenicity parameters as follows: micronuclei, binucleation, and nuclear buds. For measuring cytotoxicity, the following metanuclear changes were evaluated: pyknosis, karyolysis, and karyorrhexis, in a double-blind manner. The repair index was also evaluated in this setting. RESULTS: The human immunodeficiency virus group showed high frequencies of micronuclei (p=0.05), binucleated cells (p=0.001), and nuclear buds (p=0.03). In the cytotoxicity parameters, represented by the cell death phases, there was an increase with statistical difference (p≤0.05) in the karyorrhexis frequency (p=0.05). Additionally, repair index was decreased in the human immunodeficiency virus group. CONCLUSION: These results indicate that human immunodeficiency virus -infected individuals undergoing antiretroviral therapy have cytogenetic changes in oral mucosal cells.
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RESUMO A Covid-19 chegou rapidamente à periferia das grandes cidades brasileiras, a qual é socialmente mais vulnerável. A baixa capacidade de testagem resulta na adoção de medidas sem informações consistentes sobre o comportamento da doença e interfere na adoção de ações de controle. Objetivou-se estimar a prevalência de infecção por SARS-CoV-2 na população da Região Metropolitana da Baixada Santista (RMBS) e analisar impactos da vulnerabilidade social e de políticas públicas implementadas em contextos de desigualdades. Estudo de caráter quantitativo, transversal, mediante inquérito sorológico seriado e aplicação de questionário em amostragem populacional estratificada e coleta domiciliar, nos nove municípios da RMBS. Conclui-se que a soroprevalência medida foi de 1,4% na primeira fase, e de 2,2% na segunda; permitindo estimar 15 pessoas infectadas para cada caso notificado na primeira fase, e 10 na seguinte. A letalidade foi recalculada para 0,40% e 0,48% em cada fase, aproximando-se da casuística internacional. Pessoas mais vulneráveis são as mais atingidas pela pandemia, devendo ser consideradas: informalidade no trabalho, baixa renda, cor da pele autorreferida como preta ou parda e informações ambivalentes quanto à prevenção. Os resultados reforçam a importância do isolamento social e da adoção de medidas econômicas e sociais protetivas destinadas às populações vulneráveis.
ABSTRACT Covid-19 dramatically impacted socially vulnerable regions at the outskirts of large Brazilian cities. Besides, low testing capacity resulted in the lack of proper control measures due to inconsistent information on the disease's behavior. This study aimed to estimate prevalence of SARS-CoV-2 antibodies among the Baixada Santista Metropolitan Region (RMBS) population and the impacts of social vulnerability and public policies implemented within an environment of inequality. A quantitative, cross-sectional study, through a serial serological survey and the application of a questionnaire in stratified population sampling and home drew, in nine municipalities of RMBS. Seroprevalence was 1.4% in the first and 2.2% in the second phase, allowing to estimate 15 infected people for each case notified in the first phase, and 10 in the following. Lethality was recalculated to 0.40% and 0.48% in each phase, approaching the international rates. Socially vulnerable people were the most affected by the pandemic. Informal work, low income, self-reported skin color as black or brown, and ambivalent information regarding prevention should be considered as risk factors. Our results reinforce the relevance of social isolation and the adoption of protective economic and social measures, especially for socially vulnerable populations.
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Advancements in next-generation sequencing and bioinformatics have expanded our knowledge of the diversity of viruses (pathogens and non-pathogens) harbored by mosquitoes. Hubei reo-like virus 7 (HRLV 7) was recently detected by the virome analysis of fecal samples from migratory birds in Australia. We now report the detection of RNA-dependent RNA polymerase sequences of HRLV 7 in pools of Aedes aegypti and Culex quinquefasciatus mosquitoes species from the Brazilian Amazon forest. Phylogenetic inferences indicated that all HRLV 7 strains fall within the same independent clade. In addition, HRLV 7 shared a close ancestral lineage with the Dinovernavirus genus of the Reoviridae family. Our findings indicate that HRLV 7 is present in two species of mosquitoes.
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Aedes/virologia , Culex/virologia , Orthoreovirus de Mamíferos/enzimologia , Orthoreovirus de Mamíferos/genética , RNA Polimerase Dependente de RNA/genética , Animais , Brasil , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , RNA Viral/genética , Floresta Úmida , Infecções por ReoviridaeRESUMO
Objetivo: Traçar um perfil sociodemográfico de pacientes com insuficiência renal aguda internados em unidade de terapia intensiva e identificar a prevalência dos principais fatores das internações, assim como as patologias de base associadas à insuficiência renal aguda. Métodos: Estudo transversal, observacional, analítico e descritivo, realizado por intermédio do levantamento dos prontuários de pacientes com insuficiência renal aguda, internados em Unidade de Terapia Intensiva, no período de janeiro de 2011 a maio de 2013. Resultados: Os pacientes tinham idade média de 56,5 anos e faixa etária predominante de 60 a 70 anos; 59% eram do sexo masculino, com predominância de raça branca (65%) e negra (34%), procedentes das cidades de Santos (35,5%) e de São Vicente (24%), sendo as principais causas de internação: desequilíbrio hidroeletrolítico (43%), insuficiência respiratória (27%) e pacientes pós-cirúrgicos (9,5%). A média de permanência na unidade de terapia intensiva foi de 20 dias. As patologias de base predominantes foram neoplasias (22,5%), diabetes (18,5%), cardiopatias (17%) e ausência de tratamentos anteriores (86,5%). Conclusão: A alta taxa de pacientes que não receberam tratamento anterior pode ser um indício de deficiência na Atenção Primária e Secundária na saúde. A alta incidência em homens brancos, na terceira idade, pode indicar a necessidade de campanhas educativas dirigidas à esta população. A altíssima taxa de mortalidade pode sugerir a necessidade de se reverem condutas médicas e de enfermagem, com o intuito de minimizar riscos a pacientes com insuficiência renal aguda.(AU)
Objective: To delineate a sociodemographic profile of patients with acute renal failure admitted to an intensive care unit, and to identify the prevalence of the main factors for admission, as well as the basic pathologies associated with acute renal failure. Methods: This is a cross-sectional, observational, analytical and descriptive study, performed through a survey of the acute renal failure patients' records who were admitted to an intensive care unit, from January 2011 to May 2013. Results: Patients' mean age was 56.5 years; the predominant age group was 60-70 years; 59% were male, with a predominance of Caucasians (65%) and black people (34%), coming predominantly from the cities of Santos (35.5%) and São Vicente (24%), with the main causes of hospitalization being water-electrolyte imbalance (43%), respiratory failure (27%), and post-surgical condition (9.5%). The average length of stay in the intensive care unit was 20 days. The predominant basic conditions were: neoplasms (22.5%), diabetes (18.5%), heart diseases (17%) and absence of previous treatments (86.5%). Conclusion: The high rate of patients who received no previous treatment may indicate deficiency in primary and secondary healthcare. The high incidence in elderly white men may indicate the need for educational campaigns directed at this population. The high mortality rate may suggest the need to review medical and nursing behavior in order to minimize risks to patients with acute renal failure.(AU)
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hospitalização , Unidades de Terapia Intensiva , Insuficiência Renal Crônica/epidemiologia , Estudos Transversais/métodosRESUMO
A Leucemia Mieloide Crônica (LMC) é uma neoplasia mieloproliferativa originada, em 95% dos casos, por uma anormalidadecitogenética que se caracteriza pela translocação recíproca entre os cromossomos 9 e 22 t(9; 22) (q34; q11), resultandono cromossomo Philadelphia (Ph). Considerando que a cura da LMC só é possível com um transplante de medulaóssea bem-sucedido e que existem casos de resistência ao inibidor de tirosina quinase Mesilato de Imatinibe, fármacode primeira escolha para o tratamento, é importante que se conheça detalhadamente os genes e proteínas alterados naLMC, favorecendo a efetividade de estratégias terapêuticas, a otimização do diagnóstico e a detecção de doença residualmínima. Dentre as novas abordagens terapêuticas para a LMC está a terapia gênica, que dependendo do gene alvo, podetambém ser eficiente para o tratamento de outras neoplasias. Dentro deste contexto, os objetivos do trabalho foram:realizar a clonagem molecular de um fragmento de DNA do gene EZH2, alvo promissor da terapia gênica, que provocaalteração epigenética na LMC e em diversas neoplasias; bem como contribuir para outros trabalhos de manipulação gênicainterespécies, os quais tem grande contribuição para a área da saúde. Para isso, o gene EZH2 foi isolado a partir do DNAgenômico de sangue periférico de pacientes com LMC e posteriormente clonado em sistemas procariotos. Dessa forma,foram realizados, definidos e comprovados os procedimentos de manipulação gênica interespécies e discutido o futuro dabiotecnologia no auxílio a pesquisas e a tratamentos, com foco na LMC.
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasia, caused in 95 % of the cases by a cytogenetic abnormalitycharacterized by the reciprocal translocation between chromosomes 9 and 22 t(9; 22) (q34; q11), resulting in Philadelphiachromosome (Ph).Considering that CML cure is only possible with a successful bone marrow transplantation and that thereare resistance cases to the tyrosine kinase inhibitor Imatinib Mesylate, prescribed in first line drug treatment; it is importantto know in detail the genes and proteins that are possibly altered in CML, favoring effective therapeutic strategies, optimizeddiagnosis and minimal residual disease detection. Among the new therapeutic approaches to CML is gene therapy, which,depending on the target gene, can be efficient to other neoplasms treatment. In this context, the aims of this work were:to proceed the molecular cloning of a DNA fragment from EZH2 gene, potential target for gene therapy, that promotesepigenetic alteration in CML and in many neoplasms; as well as to contribute to studies related to interspecies gene transferthat have high contribution to health. For this reason, the EZH2 gene was isolated from peripheral blood genomic DNAfrom CML patients and cloned in prokaryotic systems. Therefore, in this study, we proceed, defined and proved the interspeciesgene transfer procedures and discussed the future of biotechnology in researches and treatments, especially in CML.
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Humanos , Biotecnologia , Leucemia , Leucemia Mielogênica Crônica BCR-ABL Positiva , Clonagem Molecular , Terapia Genética , Proto-OncogenesRESUMO
ABSTRACT Objective Ascertain the prevalence of depressive and anxiety symptoms in medical students, considering data in the literature that indicate higher vulnerability to emotional disorders in this population. Methods A descriptive cross-sectional study with a sample of 657 (98%) students. The instruments used were: questionnaire of socioeconomic-demographic characteristics, Beck Depression Inventory and Beck Anxiety Inventory. Results Predominance of the female gender (61%), aged between 17 and 30 years (98%), Catholic religion (64.2%) from the city of São Paulo (40.7%) and other cities in the state (35.7%); 30% presented depressive symptoms and 21% anxiety symptoms. Female students had higher scores both for depression (34.8%) and for anxiety (26.8%). As regards the course year, the highest rates were found in the 5th year (40.7%) for depression and in the 2nd year for anxiety (28.8%). Conclusion The data obtained in this study (30%) agreed with the literature regarding the prevalence of depressive symptoms in medical students, but this index was higher compared to the population in general (15.1% to 16.8%), and related to people in São Paulo city (18.5%). Concerning anxiety the rates found were slightly lower than those in specific literature but higher than those in literature for the population in general (8% to 18%) and in city São Paulo (16.8%). These indices indicate that the school of medicine may play a role as a predisposing and/or triggering factor in some students. The results suggest that more attention should be directed to 5th year students, who are beginning the internship period.
RESUMO Objetivo Verificar a prevalência de sintomas depressivos e ansiosos em acadêmicos de Medicina, considerando-se dados da literatura que apontam maior vulnerabilidade para distúrbios emocionais nessa população. Métodos Estudo transversal descritivo com amostra de 657 (98%) alunos, realizado na cidade de Santos, região do litoral paulista. Instrumentos utilizados questionário de características socioeconômico-demográficas, Inventário para Depressão de Beck e Inventário de Ansiedade de Beck. Resultados Predominância do gênero feminino (61%), faixa etária entre 17 e 30 anos (98%), religião católica (64,2%), procedente da cidade de São Paulo (40,7%) e de outras cidades do interior do estado (35,7%); 30% apresentaram sintomas depressivos e 21%, sintomas ansiosos. O gênero feminino obteve escores mais elevados tanto para depressão (34,8%) quanto para ansiedade (26,8%). Em relação ao ano cursado, índices mais elevados para depressão foram constatados no 5º ano (40,7%) e para ansiedade no 2º ano (28,8%). Conclusão Os dados obtidos neste estudo (30%) foram concordantes quanto à prevalência de sintomas depressivos encontrados na literatura referentes a estudantes de Medicina e mais elevados em relação à população em geral (15,1% a 16,8%) e na cidade de São Paulo (18,5%). Quanto à ansiedade, foram verificados índices ligeiramente inferiores aos da literatura específica e superiores aos da literatura na população em geral (8% a 18%) e na cidade de São Paulo (16,8%). Tais índices indicam que a escola médica pode atuar como fator predisponente ou desencadeante em alguns alunos. Resultados sugerem maior atenção para com os alunos do 5º ano, período referente ao início do internato.
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INTRODUCTION: In Brazil, the use of antiretrovirals is widespread: more than 260,000 individuals are currently undergoing treatment. We conducted a survey targeting antiretroviral-naïve individuals who were initiating antiretroviral therapy (ART) according to local guidelines. This survey covered five Brazilian regions. METHODS: The HIV Threshold Survey methodology (HIV-THS) of the World Health Organization was utilized, and subjects were selected from seven highly populated cities representative of all Brazilian macro-regions. Dried blood spots (DBS) were collected on SS903 collection cards and were transported by regular mail at room temperature to a single central laboratory for genotyping. RESULTS: We analysed samples from 329 individuals initiating highly active antiretroviral therapy (HAART), 39 (11.8%) of whom were harbouring transmitted drug resistance (TDR). The mean CD4+ T cell count was 253 cells/µL, and the mean viral load was 142,044 copies/mL. The regional prevalence of resistance was 17.0% in the Northeast, 12.8% in the Southeast, 10.6% in the Central region, 8.5% in the North and 8.5% in the South. The inhibitor-specific TDR prevalence was 6.9% for nucleoside reverse transcriptase inhibitors, 4.9% for non-nucleoside reverse transcriptase inhibitors and 3.9% for protease inhibitors; 3.6% of individuals presented resistance to more than one class of inhibitors. Overall, there were trends towards higher prevalences of subtype C towards the South and subtype F towards the North. Of the DBS samples collected, 9.3% failed to provide reliable results. DISCUSSION: We identified variable TDR prevalence, ranging from intermediate to high levels, among individuals in whom HIV disease progressed, thus implying that resistance testing before initiating ART could be effective in Brazil. Our results also indicate that the use of DBS might be especially valuable for providing access to testing in resource-limited and remote settings.
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Farmacorresistência Viral , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Adolescente , Adulto , Idoso , Sangue/virologia , Brasil , DNA Viral/genética , Dessecação/métodos , Feminino , Genótipo , Técnicas de Genotipagem , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Manejo de Espécimes/métodos , Adulto JovemRESUMO
HIV has extraordinary genetic mutability, both among individuals and at the population level. However, studies of primary HIV-1 infection and serum-converters indicate that the viral population is homogeneous at the sequence level, which suggests clonal HIV transmission. It remains unclear whether this feature applies to the female population. Ten single genome amplification sequences were generated from ten individuals (five females) with recent heterosexually acquired HIV infection as determined by the serologic testing algorithm for recent HIV seroconversion. Intra-individual genetic diversity was equally low in both genders (<2 %), with mean and median variations of 0.8 and 0 %, respectively. All of the subjects were infected with clade B. Three subjects (two females) appeared to be infected by two related viral populations, and four subjects harbored non-R5 strains. Our results support the hypothesis of clonal selection for sexual transmission of HIV-1 in both genders. Future studies that generate a larger number of clones, preferably by next generation deep sequencing, are needed to confirm these results.
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Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Adulto , Brasil/epidemiologia , Feminino , Variação Genética , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , HIV-1/classificação , HIV-1/genética , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Comportamento Sexual , Adulto JovemRESUMO
BACKGROUND: Continuous long-term treatment is recommended to reduce the hepatitis B virus (HBV) viral load. However, as a consequence, resistance mutations can emerge and be transmitted to other individuals. The polymerase (POL) gene overlaps the surface (S) gene. Thus, during treatment, mutations in the POL gene may lead to changes in hepatitis B surface antigen (HBsAg). The purpose of this study was to evaluate the frequency of lamivudine and vaccine escape mutations in HBsAg-positive blood donors from the city of Santos and in untreated HBV mono-infected patients from the city of São Paulo, Brazil. METHODS: HBV DNA was extracted from 80 serum samples, of which 61 were from volunteer blood donors and 19 were from untreated HBV patients. A fragment of the POL/S genes containing 593 base pairs was amplified using nested PCR. Thirty four were PCR-positive and sequencing was performed using an ABI Prism 3130 Genetic Analyzer. Alignments and mutation mapping were performed using BioEdit software. RESULTS: HBV DNA from 21 blood donors and 13 untreated patient samples were characterized using nucleotide sequencing PCR products from the POL/S genes. We were able to detect one sample with the resistance mutation to lamivudine rtM204V + rtL180M (2.94%), which was found in a volunteer blood donor that has never used antiviral drugs. The other samples showed only compensatory mutations, such as rtL80F (5.88%), rtL80V (2.94%), rtL82V + rtV207L (2.94%), rtT128P (5.88%), rtT128N/S (2.94%) and rtS219A (5.88%). We found modifications in the S gene in 14 of the 34 samples (41.16%). The mutations detected were as follows: sM133L + sI195T (2.94%), sI195M (2.94%), sP120T (2.94%), sY100S/F (2.94%), sY100C (17.64%), sI/T126P + sQ129P (2.94%), sM198I + sF183C (2.94%) and sS210R (5.88%). CONCLUSIONS: Our results suggest the transmission of lamivudine-resistant forms. Thus, the evaluation of HBV-infected subjects for lamivudine resistance would improve treatment regime. Moreover, the mutations in the S gene may impair HBsAg antigenicity and contribute to HBsAg failure detection and vaccine escape.
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Antivirais/farmacologia , Farmacorresistência Viral , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Lamivudina/farmacologia , Adulto , Brasil , DNA Viral/química , DNA Viral/genética , DNA Viral/isolamento & purificação , Erros de Diagnóstico , Reações Falso-Negativas , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Evasão da Resposta Imune , Masculino , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
BACKGROUND: Vicriviroc, a novel HIV CCR5 antagonist, demonstrated significant efficacy and favorable tolerability in phase II trials in treatment-experienced subjects, supporting further evaluation in phase III studies. METHODS: Two identical double-blind, placebo (PBO)-controlled trials in CCR5-tropic HIV-infected subjects with documented resistance to two antiretroviral classes were conducted. Subjects were randomized to vicriviroc 30 mg QD (N = 571) or PBO (N = 286) with open-label optimized background therapy (OBT) containing ≥2 fully active antiretroviral drugs. The primary endpoint was percentage of subjects with <50 copies/mL HIV RNA at 48 weeks. It was analyzed in a logistic regression with treatment (vicriviroc + OBT/PBO + OBT), use of enfuvirtide in baseline OBT (yes/no), and baseline HIV RNA (≤100,000/>100,000 copies/mL) as covariates. In addition, a pre-planned analysis to examine other efficacy and safety endpoints was conducted. RESULTS: Baseline characteristics of the pooled mITT population (vicriviroc, n = 486; PBO, n = 235) included mean HIV RNA of 4.6 log(10) copies/mL and mean CD4 count of 257 cells/µL. Approximately 60% of subjects received ≥3 active drugs in the OBT. The percentage of subjects with <50 copies/mL HIV RNA was not significantly different between vicriviroc and PBO at week 48 (64% vs 62%, p = 0.6). However, in subjects receiving ≤2 active drugs in their OBT, the proportion achieving <50 copies/mL HIV RNA was higher in those receiving vicriviroc compared with PBO (70% vs 55%, p = 0.02). CONCLUSIONS: The studies failed to show significant efficacy gains when vicriviroc was added to OBT. However, given the efficacy results of earlier vicriviroc trials and other CCR5 antagonist, studies are needed to define the role of this class of drugs in the treatment of HIV. Clinical trial identifier: http://www.clinicaltrial.gov/: VICTOR-E3 (NCT00523211) and VICTOR-E4 (NCT00474370).
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Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Receptores CCR5/metabolismo , Receptores de HIV/metabolismo , Adulto , Método Duplo-Cego , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , RNA Viral/sangue , Resultado do Tratamento , Carga Viral , Viremia/virologiaRESUMO
The environmental contamination by geohelminths represents a world public health problem and has been well documented by several authors. However, few papers describe the presence of such contamination in saline soils of coastal beaches. A study was performed on the beaches of the municipality of Santos in the period between May 2004 to April 2005 with the aim of determining the degree of contamination, and the correlation between contamination level and seasonal conditions and characteristics of the environment. Of the 2,520 samples analyzed, 18.2% (458) were contaminated, 32.3% (148) of which were localized in children's recreational areas (playgrounds). The parasite profile found in the analyzed samples indicated the presence of several zoonotic parasites: Ancylostoma larvae (82.5%), Toxocara sp. eggs (59.4%), Ancylostomidae-like eggs (37.1%), coccid oocysts (13.5%), Trichostrongylus sp. eggs and larvae, Ascaris lumbricoides eggs, (11.6%), Entamoeba sp. cysts (10.0%), Strongyloides sp. (4.8%), several free nematoids and some non-identified parasitic structures (3.3%). It was established that the highest frequency of parasitic structures occurred in the months between May and October 2004, and from February to March 2005. An increase in the diversity of parasitic forms was documented in the months between February to December 2004 and from January to April 2005, these periods having the highest rainfall.
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Praias , Entamoeba/isolamento & purificação , Helmintos/isolamento & purificação , Solo/parasitologia , Animais , Brasil , Helmintos/classificação , Contagem de Ovos de Parasitas , Chuva , Estações do Ano , Dióxido de SilícioRESUMO
The environmental contamination by geohelminths represents a world public health problem and has been well documented by several authors. However, few papers describe the presence of such contamination in saline soils of coastal beaches. A study was performed on the beaches of the municipality of Santos in the period between May 2004 to April 2005 with the aim of determining the degree of contamination, and the correlation between contamination level and seasonal conditions and characteristics of the environment. Of the 2,520 samples analyzed, 18.2 percent (458) were contaminated, 32.3 percent (148) of which were localized in children's recreational areas (playgrounds). The parasite profile found in the analyzed samples indicated the presence of several zoonotic parasites: Ancylostoma larvae (82.5 percent), Toxocara sp. eggs (59.4 percent), Ancylostomidae-like eggs (37.1 percent), coccid oocysts (13.5 percent), Trichostrongylus sp. eggs and larvae, Ascaris lumbricoides eggs, (11.6 percent), Entamoeba sp. cysts (10.0 percent), Strongyloides sp. (4.8 percent), several free nematoids and some non-identified parasitic structures (3.3 percent). It was established that the highest frequency of parasitic structures occurred in the months between May and October 2004, and from February to March 2005. An increase in the diversity of parasitic forms was documented in the months between February to December 2004 and from January to April 2005, these periods having the highest rainfall.
A contaminação ambiental por geohelmintos representa um problema mundial de saúde pública e tem sido bem documentada por diversos autores. No entanto, poucos trabalhos descrevem a presença de contaminação em solos salinos de praias litorâneas. Este estudo foi realizado nas praias do município de Santos no período entre maio de 2004 a abril de 2005 com o objetivo de determinar o grau de contaminação, e possíveis correlações entre sazonalidade e características ambientais. Das 2.520 amostras analisadas, 18,2 por cento (458) estavam contaminadas, 32,3 por cento (148) das quais foram localizadas em areas de lazer das crianças(playgrounds). O perfil parasitário encontrado nas amostras analisadas indicaram a presença de vários parasitos com potencial zoonótico: larvas de Ancylostoma (82,5 por cento), ovos de Toxocara sp (59,4 por cento), ovos semelhantes aos de Ancilostomídeos (37,1 por cento), oocistos de coccídeos (13,5 por cento), ovos de Trichostrongylus sp., ovos de Ascaris lumbricoides, (11,6 por cento), cistos de Entamoeba sp. (10,0 por cento), Strongyloides sp. (4,8 por cento), vários nematóides de vida livre e algumas estruturas parasitárias não identificadas que podem corresponder a um parasita (3,3 por cento). Foi estabelecido que a maior frequência de estruturas parasitárias ocorreu nos meses entre maio e outubro de 2004, e de fevereiro a março de 2005. Um aumento na diversidade de formas parasitárias foi documentado nos meses entre fevereiro a dezembro de 2004 e de janeiro a abril de 2005, esses períodos com a maior pluviosidade.
Assuntos
Animais , Praias , Entamoeba/isolamento & purificação , Helmintos/isolamento & purificação , Solo/parasitologia , Brasil , Helmintos/classificação , Contagem de Ovos de Parasitas , Chuva , Estações do Ano , Dióxido de SilícioRESUMO
Santos is a Brazilian port city with high HIV incidence, high primary antiretroviral resistance levels, high HIV-1 BF recombinants prevalence, and high rates of antiretroviral virologic failure. We evaluated factors related to virologic failure after 48 weeks of HAART in this population. We compared demographic and HIV profiles among 43 individuals with virologic failure (group 1) and 37 with virologic success (group 2) after 48 weeks of HAART initiation. The overall primary antiretroviral resistance prevalence was 31.2%; 46.5% in group 1 and 13.5% in group 2 (p < 0.005). Nine patients from group 1 and seven from group 2 were infected by F or BF strains. Fifteen individuals presented with NRTI mutations, 13 with NNRTI mutations, three with PI mutations, and five with NRTI and NNRTI mutations. No significant differences were observed in baseline viral load, CD4, clade assignment, antiretrovirals used, or demographics among groups or patients harboring resistant versus wild-type viruses. In this region, there was a high prevalence of antiretroviral resistance among long standing infected patients whose disease had progressed. This finding supports the concept that resistance testing prior to ART initiation is cost effective. The association between primary antiretroviral resistance and virologic failure may suggest that primary resistance greatly impairs antiretroviral activity.
Assuntos
Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Brasil , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Estudos de Casos e Controles , Farmacorresistência Viral/genética , Feminino , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Carga ViralRESUMO
Acanthamoeba and Naegleria species are free-living amoebae (FLA) found in a large variety of natural habitats. The prevalence of such amoebae was determined from dust samples taken from public non-hospital internal environments with good standards of cleanliness from two campuses of the same University in the city of Santos (SP), Brazil, and where young and apparently healthy people circulate. The frequency of free-living amoebae in both campuseswas 39 percent and 17 percent respectively, with predominance of the genus Acanthamoeba. On the campus with a much larger number of circulating individuals, the observed frequency of free-living amoebae was 2.29 times larger (P< 0.00005). Two trophozoite forms of Naegleria fowleri, are the only species of this genus known to cause primary amoebian meningoencephalitis, a rare and non-opportunistic infection. We assume that the high frequency of these organisms in different internal locations represents some kind of public health risk.
Assuntos
Acanthamoeba/isolamento & purificação , Poeira/análise , Meio Ambiente , Naegleria/isolamento & purificação , Universidades , Acanthamoeba/patogenicidade , Brasil , Cidades , Naegleria/patogenicidadeRESUMO
HIV-1 from infected subjects has been characterized in order to provide a more accurate view of the strains that are currently found in a given region. In this report, we focused on characterizing the pol gene diversity obtained from newly diagnosed patients in Santos metropolitan area, Brazil. This region is composed of nine cities and an international port. Analysis of the 33 samples revealed that 22 strains belonged to subtype B, 4 to subtype F, and 2 to subtype C; 5 strains were B/F recombinants. Our results demonstrated that 18.2% of samples were primary antiretroviral resistance genotypic mutations, with high-level resistance to reverse transcriptase inhibitors in both subtypes B and F and in recombinant forms B/F. Our data revealed that the primary antiretroviral resistance genotypic mutations should be carefully investigated in developing countries with widespread access to antiretrovirals, such as Brazil.