BACKGROUND The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS. OBJECTIVE To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients. METHODS Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis. FINDINGS Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms. MAIN CONCLUSIONS Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression.

RESUMO Os adenovírus humanos (HAdV) são notavelmente resistentes ao ambiente. Estes agentes podem servir como indicadores efetivos de contaminação fecal, tanto quanto podem atuar como agentes causadores de diferentes doenças em seres humanos. A reação em cadeia da polimerase (PCR) e mais recentemente a PCR quantitativa (qPCR) são amplamente usadas para detecção de agentes virais em matrizes ambientais. No presente estudo, PCR e SYBR(r)Green qPCR foram comparadas para a detecção de HAdV em amostras de água (55) e sedimento (20) provenientes de nascentes, poços, açudes e arroios coletadas em propriedades leiteiras. A metodologia quantitativa detectou HAdV em 87,3% das amostras de água e 80% dos sedimentos, enquanto por PCR convencional a detecção foi de 47,3% e 35%, respectivamente.

SUMMARY Human Adenoviruses (HAdV) are notably resistant in the environment. These agents may serve as effective indicators of fecal contamination, and may act as causative agents of a number of different diseases in human beings. Conventional polymerase chain reaction (PCR) and, more recently, quantitative PCR (qPCR) are widely used for detection of viral agents in environmental matrices. In the present study PCR and SYBR(r)Green qPCR assays were compared for detection of HAdV in water (55) and sediments (20) samples of spring and artesian wells, ponds and streams, collected from dairy farms. By the quantitative methodology HAdV were detected in 87.3% of the water samples and 80% of the sediments, while by the conventional PCR 47.3% and 35% were detected in water samples and sediments, respectively.

The aim of the present study was to investigate the association between HPV-DNA and micronucleus (MN) frequency in women with normal cervical cytology. A total of 158 normal cervical smears were analyzed cytologically. The HPV genome was amplified using the GP5+/bioGP6+ consensus primers. HPV-DNA of high-risk types 16, 18, 31, 33, 39, 45 and 59 were also investigated. Of the 158 samples, 20 (12.7%) and 47 (29.7%) were positive for HPV-DNA and MN, respectively. Evidence for MN was found in 11 out of 20 (55%) HPV-DNA positive samples and in 36 out of 138 (26.1%) HPV-DNA negative ones. MN presence was significantly higher in HPV-DNA positive samples (p = 0.016). On the other hand, the absence of MN observed in a considerable number of HPV-DNA negative samples (102) may be of great value in predicting the absence of HPV. The mean age of HPV-DNA positive women (34.2 ± 12.6) was significantly lower than the mean age of HPV-DNA negative women (43.9 ± 13.7) (p = 0.003). Infection by one or multiple HPV types was found in 11 out of 20 (55.0%) and 9 out of 20 (45.0%) samples, respectively. The evaluation of MN using cervical smears collected for cytology tests could, thus, be used as additional information to monitor a population's exposure to HPV.

Typical human immunodeficiency virus-1 subtype B (HIV-1B) sequences present a GPGR signature at the tip of the variable region 3 (V3) loop; however, unusual motifs harbouring a GWGR signature have also been isolated. Although epidemiological studies have detected this variant in approximately 17-50% of the total infections in Brazil, the prevalence of B"-GWGR in the southernmost region of Brazil is not yet clear. This study aimed to investigate the C2-V3 molecular diversity of the HIV-1B epidemic in southernmost Brazil. HIV-1 seropositive patients were ana-lysed at two distinct time points in the state of Rio Grande do Sul (RS98 and RS08) and at one time point in the state of Santa Catarina (SC08). Phylogenetic analysis classified 46 individuals in the RS98 group as HIV-1B and their molecular signatures were as follows: 26% B"-GWGR, 54% B-GPGR and 20% other motifs. In the RS08 group, HIV-1B was present in 32 samples: 22% B"-GWGR, 59% B-GPGR and 19% other motifs. In the SC08 group, 32 HIV-1B samples were found: 28% B"-GWGR, 59% B-GPGR and 13% other motifs. No association could be established between the HIV-1B V3 signatures and exposure categories in the HIV-1B epidemic in RS. However, B-GPGR seemed to be related to heterosexual individuals in the SC08 group. Our results suggest that the established B"-GWGR epidemics in both cities have similar patterns, which is likely due to their geographical proximity and cultural relationship.

CONTEXTO E OBJETIVO: O anticorpo anti-decarboxilase do ácido glutâmico (anti-GAD) é considerado um importante marcador no diabetes mellitus tipo 1 (DM1), cuja frequência varia segundo a população estudada e o tempo de duração da doença. Assim, o objetivo deste estudo foi determinar a frequência deste auto-anticorpo em um grupo de pacientes localizados no Sul do Brasil com mais de três anos de diagnóstico de DM1. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico com grupo controle, realizado no Laboratório de Biomedicina da Universidade Feevale. MÉTODOS: Este estudo foi realizado no período de Junho de 2007 a Dezembro de 2008, em que 109 indivíduos foram incluídos, sendo 58 destes com DM1 e 51 indivíduos sem DM1 e sem antecedentes de diabetes, que constituíram o grupo controle. RESULTADOS: No grupo DM1, a idade média foi 27 ± 1,7 anos e 50% eram homens. A média da glicemia de jejum no grupo DM1 foi 208 ± 15 mg/dL e a HbA1c média foi 8,7 ± 0.25%. No grupo controle a glicemia de jejum média e a HbA1c (hemoglobina glicosilada) foram 82 mg/dL e 5,0%, respectivamente. O anti-GAD foi positivo em 37 (63,8%) indivíduos com DM1, valores significativamente maiores quando comparados com os do grupo controle. CONCLUSÕES: Estes resultados mostram a alta prevalência do anti-GAD na população de pacientes diabéticos da região Sul do Brasil, indicando que o anticorpo está presente após um longo período de diagnóstico da doença.

CONTEXT AND OBJECTIVE: The anti-GAD (glutamic acid decarboxylase) antibody is considered to be an important marker for type 1 diabetes mellitus (DM1), with frequency that varies depending on the population studied and the duration of the disease. Therefore, the aim of this study was to determine the frequency of this autoantibody in a group of patients in southern Brazil with DM1 that had been diagnosed more than three years previously. DESIGN AND SETTING: Analytical cross-sectional study with a control group conducted at the Biomedicine Laboratory of Universidade Feevale. METHODS: This study was conducted between June 2007 and December 2008, and 109 individuals were enrolled during this period. Fifty-eight were DM1 patients and 51 were individuals free from DM1 and without any history of diabetes, who constituted the control group. RESULTS: In the DM1 group, the mean age was 27 ± 1.7 years and 50% were men. The mean fasting blood glucose in the DM1 group was 208 ± 15 mg/dl and mean HbA1c (glycosylated hemoglobin) was 8.7 ± 0.25%. In the control group, the mean fasting blood glucose and HbA1c were 82 mg/dl and 5.0% respectively. Thirty-seven individuals with DM1 (63.8%) were positive for anti-GAD, and this proportion was significantly larger than in the control group. CONCLUSIONS: These results show the high prevalence of anti-GAD in the population of diabetic patients in southern Brazil, thus indicating that the antibody was still present a long time after the disease had been diagnosed.

OBJETIVO: Avaliar as alterações metabólicas associadas à terapia anti-retroviral potente em pacientes HIV-positivos e identificar fatores de risco associados. MÉTODOS: Estudo retrospectivo com 110 pacientes HIV-positivos que estavam sob terapia anti-retroviral potente (HAART) na cidade de Porto Alegre (RS), entre janeiro de 2003 e março de 2004. Os dados coletados incluem variáveis demográficas, tabagismo, diabetes mellitus, níveis de colesterol e triglicerídeos, estágio da infecção viral, terapia anti-retroviral e co-infecção com hepatite C. A análise multivariada para medidas repetidas (General Linear Model procedure for Repeated Measures) foi utilizada para testar a interação entre o efeito do uso de HAART e o uso de inibidores de protease ou co-infecção por hepatite C. RESULTADOS: Foram observados aumentos significativos nos níveis de colesterol total, triglicerídeos e glicose após o tratamento com HAART (p<0.001, para todas as variáveis). No entanto, nenhuma interação do tratamento com inibidores de protease foi observada para colesterol total, glicose e triglicerídeos (interação tratamento*inibidores de protease p=0.741, p=0.784 e p=0.081, respectivamente). Uma associação entre os níveis de colesterol total e co-infecção por HCV foi observada tanto antes como após o tratamento (efeito da co-infecção por hepatite C, p=0.011). Os níveis de glicose foram aumentados pelo uso da HAART (efeito do tratamento, p=0.036), sendo este dependente da co-infecção por hepatite C (efeito interação tratamento*hepatite C = 0.018). Gênero, tabagismo, uso de drogas intravenosas e idade não influenciaram significativamente os níveis de colesterol total, triglicerídeos e glicose durante o tratamento. CONCLUSÕES: Pacientes infectados pelo vírus da hepatite C no início do tratamento tiveram aumento menos significativo nos níveis de colesterol total. Os resultados reforçam as evidências do papel da HAART no desenvolvimento de desordens metabólicas.

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (p<0.001 for all variables), but no interaction with protease inhibitors was seen for total cholesterol, glucose and triglyceride levels (interaction treatment*protease inhibitors p=0.741, p=0.784, and p=0.081, respectively). An association between total cholesterol levels and HCV coinfection was found both at baseline and follow-up (effect of HCV coinfection, p=0.011). Glucose levels were increased by HAART (treatment effect, p=0.036), but the effect was associated to HCV coinfection (treatment*HCV effect, p=0.018). Gender, smoking habit, intravenous drug use and age were not significantly associated with cholesterol, triglyceride and glucose changes. CONCLUSIONS: HCV-infected patients at baseline were significantly less likely to develop hypercholesterolemia. The results provide further evidence of the role of HAART for the development of metabolic disturbances.

OBJETIVO: Evaluar las alteraciones metabólicas asociadas a la terapia anti-retroviral potente en pacientes HIV-positivos e identificar factores de riesgo asociados. MÉTODOS: Estudio retrospectivo con 110 pacientes HIV-positivos que estaban en terapia anti-retroviral potente (HAART) en la ciudad de Porto Alegre (Sur de Brasil), entre enero de 2003 y marzo de 2004. Los datos colectados incluyen variables demográficas, tabaquismo, diabetes mellitas, niveles de colesterol y triglicéridos, fase de la infección viral, terapia anti-retroviral y co-infección con hepatitis C. El análisis multivariado para medidas repetidas (General Linear Model procedure for Repeated Measures) fue utilizada para analizar la interacción entre el efecto de uso de HAART y el uso de inhibidores de proteasa o co-infección por hepatitis C. RESULTADOS: Fueron observados aumentos significativos en los niveles de colesterol total, triglicéridos y glucosa posterior al tratamiento con HAART (p<0.001, para todas las variables). Sin embargo, ninguna interacción del tratamiento con inhibidores de proteasa fue observada para colesterol total, glucosa y triglicéridos (interacción tratamiento *inhibidores de proteasa p=0.747, p= 0.784 y p= 0.081, respectivamente). Una asociación entre los niveles de colesterol total y co-infección por HCV fue observada tanto antes como después del tratamiento (efecto de la co-infección por hepatitis C, p= 0.0011). Lo niveles de glucosa fueron aumentados por el uso de la HAART (efecto del tratamiento, p= 0.036), siendo este dependiente de la co-infección por hepatitis C (efecto interacción tratamiento *hepatitis C p= 0.018). Género, tabaquismo, uso de drogas intravenosas y edad no influenciaron significativamente los niveles de colesterol total, triglicéridos y glucosa durante el tratamiento. CONCLUSIONES: Pacientes infectados por el virus de la hepatitis C en el inicio del tratamiento tuvo aumento menos significativo en los niveles de colesterol total. Los resultados refuerzan las evidencias del papel de la HAART en el desarrollo de desórdenes metabólicos.

OBJETIVO: Avaliar as alterações metabólicas associadas à terapia anti-retroviral potente em pacientes HIV-positivos e identificar fatores de risco associados. MÉTODOS: Estudo retrospectivo com 110 pacientes HIV-positivos que estavam sob terapia anti-retroviral potente (HAART) na cidade de Porto Alegre (RS), entre janeiro de 2003 e março de 2004. Os dados coletados incluem variáveis demográficas, tabagismo, diabetes mellitus, níveis de colesterol e triglicerídeos, estágio da infecção viral, terapia anti-retroviral e co-infecção com hepatite C. A análise multivariada para medidas repetidas (General Linear Model procedure for Repeated Measures) foi utilizada para testar a interação entre o efeito do uso de HAART e o uso de inibidores de protease ou co-infecção por hepatite C. RESULTADOS: Foram observados aumentos significativos nos níveis de colesterol total, triglicerídeos e glicose após o tratamento com HAART (p<0.001, para todas as variáveis). No entanto, nenhuma interação do tratamento com inibidores de protease foi observada para colesterol total, glicose e triglicerídeos (interação tratamento*inibidores de protease p=0.741, p=0.784 e p=0.081, respectivamente). Uma associação entre os níveis de colesterol total e co-infecção por HCV foi observada tanto antes como após o tratamento (efeito da co-infecção por hepatite C, p=0.011). Os níveis de glicose foram aumentados pelo uso da HAART (efeito do tratamento, p=0.036), sendo este dependente da co-infecção por hepatite C (efeito interação tratamento*hepatite C = 0.018). Gênero, tabagismo, uso de drogas intravenosas e idade não influenciaram significativamente os níveis de colesterol total, triglicerídeos e glicose durante o tratamento. CONCLUSÕES: Pacientes infectados pelo vírus da hepatite C no início do tratamento tiveram aumento menos significativo nos níveis de colesterol total. Os resultados reforçam as evidências do papel da HAART no desenvolvimento de desordens metabólicas.

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (p<0.001 for all variables), but no interaction with protease inhibitors was seen for total cholesterol, glucose and triglyceride levels (interaction treatment*protease inhibitors p=0.741, p=0.784, and p=0.081, respectively). An association between total cholesterol levels and HCV coinfection was found both at baseline and follow-up (effect of HCV coinfection, p=0.011). Glucose levels were increased by HAART (treatment effect, p=0.036), but the effect was associated to HCV coinfection (treatment*HCV effect, p=0.018). Gender, smoking habit, intravenous drug use and age were not significantly associated with cholesterol, triglyceride and glucose changes. CONCLUSIONS: HCV-infected patients at baseline were significantly less likely to develop hypercholesterolemia. The results provide further evidence of the role of HAART for the development of metabolic disturbances.

OBJETIVO: Evaluar las alteraciones metabólicas asociadas a la terapia anti-retroviral potente en pacientes HIV-positivos e identificar factores de riesgo asociados. MÉTODOS: Estudio retrospectivo con 110 pacientes HIV-positivos que estaban en terapia anti-retroviral potente (HAART) en la ciudad de Porto Alegre (Sur de Brasil), entre enero de 2003 y marzo de 2004. Los datos colectados incluyen variables demográficas, tabaquismo, diabetes mellitas, niveles de colesterol y triglicéridos, fase de la infección viral, terapia anti-retroviral y co-infección con hepatitis C. El análisis multivariado para medidas repetidas (General Linear Model procedure for Repeated Measures) fue utilizada para analizar la interacción entre el efecto de uso de HAART y el uso de inhibidores de proteasa o co-infección por hepatitis C. RESULTADOS: Fueron observados aumentos significativos en los niveles de colesterol total, triglicéridos y glucosa posterior al tratamiento con HAART (p<0.001, para todas las variables). Sin embargo, ninguna interacción del tratamiento con inhibidores de proteasa fue observada para colesterol total, glucosa y triglicéridos (interacción tratamiento *inhibidores de proteasa p=0.747, p= 0.784 y p= 0.081, respectivamente). Una asociación entre los niveles de colesterol total y co-infección por HCV fue observada tanto antes como después del tratamiento (efecto de la co-infección por hepatitis C, p= 0.0011). Lo niveles de glucosa fueron aumentados por el uso de la HAART (efecto del tratamiento, p= 0.036), siendo este dependiente de la co-infección por hepatitis C (efecto interacción tratamiento *hepatitis C p= 0.018). Género, tabaquismo, uso de drogas intravenosas y edad no influenciaron significativamente los niveles de colesterol total, triglicéridos y glucosa durante el tratamiento. CONCLUSIONES: Pacientes infectados por el virus de la hepatitis C en el inicio del tratamiento tuvo aumento menos significativo en los niveles de colesterol total. Los resultados refuerzan las evidencias del papel de la HAART en el desarrollo de desórdenes metabólicos.