TLR9 2848 G/A Gene Polymorphism in HCV+, HIV+, and HCV+/HIV+ Individuals.

Background: Host genetic factors play a major role with respect to susceptibility to infections. Many polymorphisms of the Toll-like receptors (TLRs), members of the innate immune response, are directly associated with the clinical outcomes following infection. The 2848 G/A variant (rs352140) of the TLR9 gene is associated with increased TLR9 expression. However, the impact of the genotypes of this SNP on HIV+, HCV+, and HCV+/HIV+ individuals is still debated. Materials and Methods: This study investigated the 2848 G/A polymorphism in HCV infection, HIV infection, and HCV/HIV co-infection in a large sample of Brazilians (n = 1,182). Groups were initially compared without considering stratification by ethnicity and subsequently stratifying individuals between whites and non-whites. Results: Considering non-white individuals, a significant difference between the HIV+/HCV+ group and controls was observed with the GG genotype serving as a protective factor (p = 0.023). Additionally, significant allelic differences were observed between the HCV+ group and controls (p = 0.042); between the HIV+/HCV+ group and controls (p = 0.011); and between the HIV+/HCV+ group and HIV+ individuals (p = 0.047). However, all significant results were lost following adjustment for multiple comparisons (p > 0.05). Conclusion: Although our initial results indicated a potential influence of the rs352140 genotype on host altered susceptibility to viral infections, following correction for multiple comparisions the standard (p < 0.05) for statistical association was lost. This may be due to insufficient sample size as we were examining many different associations. Thus, a larger study is warranted to further pursue this topic.

Investigation of SIRT1 gene variants in HIV-associated lipodystrophy and metabolic syndrome.

HIV-infected individuals on chronic use of highly active antiretroviral therapy (HAART) are more likely to develop adipose tissue and metabolic disorders, such as lipodystrophy (LD) and metabolic syndrome (MetS). The development of these phenotypes is known to be multifactorial. Thus, variants in genes implicated in adipogenesis and lipid metabolism may increase susceptibility to LD and MetS. Sirtuin 1 (SIRT1) may influence the outcome of these disturbances due to its role in the regulation of transcription factors involved in energy regulation. Therefore, we genotyped four polymorphisms located in SIRT1 (rs2273773 T>C, rs12413112 G>A, rs7895833 A>G, rs12049646 T>C) in 832 HIV-infected patients receiving HAART by real-time polymerase chain reaction. The prevalence of LD was 55.8% and MetS was 35.3%. Lipoatrophy was the most prevalent subtype in all samples (38.0%) and showed significant difference between white and non-white individuals (P = 0.002). None of the genetic variants investigated in SIRT1 was associated with LD and MetS. White individuals and those in longer time of HAART use were more likely to develop LD. We concluded that these SIRT1 polymorphisms are not predictive factors to the development of lipodystrophy and metabolic syndrome in HIV-infected individuals from Brazil.

CCR5Δ32 in HCV infection, HCV/HIV co-infection, and HCV-related diseases.

Although a potential involvement of the CCR5Δ32 variant has already been suggested in relation to susceptibility to hepatitis C virus (HCV) infection, data from the literature is still quite controversial. Thus, our study evaluated the influence of the CCR5Δ32 allele variant in HCV infection, HCV/HIV co-infection, and HCV-related diseases in individuals from southern Brazil. A total of 1352 individuals were included in this study, divided into the following groups: Control (n = 274); HCV+ (n = 674); HIV+ (n = 300); HCV+/HIV+ (n = 104). Individuals from the HCV+ group were further stratified according to clinical/histological criteria, as HCV+/control (n = 124); HCV+/fibrosis (n = 268); HCV+/cirrhosis (n = 190); HCV+/hepatocarcinoma (n = 92). Considering all individuals included in this study, the following genotype frequencies were observed: wild-type homozygous (wt/wt), 88.76%; heterozygous (wt/Δ32), 10.72%; variant homozygous (Δ32/Δ32), 0.52%. Genotypic frequencies were very similar between the groups. Of note, the frequency of the Δ32 homozygous was quite similar comparing control uninfected against the HCV+ individuals (p > 0.999). The overall Δ32 allele frequency was estimated at 5.88%. Considering the number of Δ32 allele carriers and non-carriers, no statistically significant differences (p > 0.05) between the groups were observed, suggesting that the CCR5Δ32 variant does not influence the susceptibility to HCV infection, HCV/HIV co-infection, or HCV-related diseases in individuals from southern Brazil.

Endosomal toll-like receptor gene polymorphisms and susceptibility to HIV and HCV co-infection - Differential influence in individuals with distinct ethnic background.

The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV-), taking into account their ethnic background. Amongst the 357 HIV+ individuals with available data concerning HCV infection, 98 were positive. In European descendants, the TLR9 rs5743836 C carriers displayed a higher susceptibility to HIV infection [dominant, Odds Ratio (OR)=1.53; 95% CI: 1.05-2.23; P=0.027]. In African descendants, TLR9 rs5743836 CT genotype was associated with protection to HIV infection (codominant, OR=0.51; 95% CI: 0.30-0.87; P=0.013). Also, the TLR9 rs352140 AA variant genotype was associated with susceptibility to HIV+/HCV+ co-infection in African descendants (recessive, OR=2.92; 95% CI: 1.22-6.98, P=0.016). These results are discussed in the context of the different ethnic background of the studied individuals highlighting the influence of this genetic/ethnic background on the susceptibility to HIV infection and HIV/HCV co-infection in Brazilian individuals.

Effectiveness of multidisciplinary intervention on blood pressure control in primary health care: a randomized clinical trial.

BACKGROUND: Hypertension is a public health problem and a major risk factor for cardiovascular disease. The purpose of this study is to compare the effectiveness of a multidisciplinary program based on group and individual care versus group-only care, to promote blood pressure control in hypertensive patients in primary health care. METHODS: Randomized controlled clinical trial. The study was conducted within the primary health care, in two units of the Family Health Strategy, covering 11,000 individuals, in Porto Alegre, Brazil. Two hundred and 56 patients, older than 40 years old and with uncontrolled hypertension, systolic blood pressure (BP) ≥140 mmHg and/or diastolic BP ≥90 mmHg or ≥130 mmHg and/or diastolic BP ≥80 mmHg for individuals with diabetes. Eligible patients were randomly assigned to a health care program aiming for blood pressure control, with the multidisciplinary program group or with the multidisciplinary program plus personalized care group. Primary outcome measures were reduction in systolic BP from baseline to 6 months. Secondary measures included proportion of patients with systolic or diastolic BP controlled. Student t test, Pearson's chi-squared test, Fisher's exact test, Mann-Whitney U test, Wilcoxon signed-ranks test and generalized estimating equation (GEE) model were used in the analysis. RESULTS: The baseline characteristics of participants were similar between groups. After 6 months of follow-up, systolic BP decreased markedly in both groups (Δ - 11.8 mmHg [SD, 20.2] in the multidisciplinary program group and Δ - 12.9 mmHg [SD, 19.2] in the personalized care group; p < 0.001). Similarly, we noted a significant change in diastolic BP over time in both groups (Δ - 8.1 mmHg [SD, 10.8] in the multidisciplinary program group and Δ - 7.0 mmHg [SD, 11.5] in the personalized care group; p < 0.001). CONCLUSIONS: The study demonstrates similar effectiveness of a group intervention in comparison to a personalized education program in hypertension patients to achieve BP control. These findings indicate that the intervention can be for all hypertensive patients assisted in primary health care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01696318 (May 2013).

Uso de Prebióticos, Probióticos e Simbióticos nos Pré e Pós--Operatórios do Câncer Colorretal: uma Revisão / Use of Prebiotics, Probiotics and Symbiotics in Pre and Postoperative of Colorectal Cancer: a Review

No Brasil, o câncer colorretal é a segunda causa de morte mais comum entre mulheres e a terceira maisprevalente em homens. Objetivo: Revisar o uso de prebióticos, probióticos e simbióticos e suas implicações nasfases de pré e pós-operatórios no paciente com câncer colorretal. Método: Trata-se de uma revisão bibliográfica deartigos publicados entre 2008 e 2013, com busca nas bases de dados MEDLINE, LILACS e SciELO , de fevereiroa maio de 2014, com os descritores: "prebióticos", "probióticos", "câncer colorretal" e "cuidado pré-operatório".Resultados: Foram encontrados sete artigos dentro dos critérios de inclusão da pesquisa. As variedades de lactobacilosilustradas nos estudos mantiveram diferenças, no tipo, concentração e modelo de intervenção abordados. Contudo,constatou-se que o uso intervencional de probióticos, isolados ou em associação com fibras prebióticas, foi benéficonos pacientes que fizeram seu uso, tanto nos períodos pré-operatórios como pós-cirúrgicos. Os principais achadosforam: melhoria da qualidade de vida, de exames laboratoriais e no padrão de defesa imunológica. Em contrapartida,houve menor translocação bacteriana e diminuição de bactérias enteropatogênicas, frente à utilização de simbióticosem substituição aos mecanismos convencionais de preparação cirúrgica. Conclusão: Destaca-se a necessidade de maisestudos prospectivos capazes de fornecer dados mais completos e bem delineados, com cepas e quantidades específicas,a fim de proporcionar resultados mais conclusivos sobre os reais benefícios desse tipo de suplementação em pacientesoncológicos...

Influence of HLA-G polymorphisms in human immunodeficiency virus infection and hepatitis C virus co-infection in Brazilian and Italian individuals.

OBJECTIVE: This study aimed to investigate the role of Human Leukocyte Antigen (HLA)-G in the susceptibility to HIV-1 infection through the analysis of the HLA-G 3' untranslated region (UTR) polymorphisms 14 bp insertion/deletion (rs66554220) and +3142C>G (rs1063320). DESIGN: We analyzed 582 HIV-1 infected patients and 626 uninfected individuals from Brazil and Italy in a case-control study. METHODS: HLA-G polymorphisms were genotyped using PCR, PCR-RFLP assays or direct sequencing. All analyses were stratified by ethnicity. Genotypic, allelic and diplotypic frequencies were compared between HIV-1 infected subjects and controls using Chi-square or Fischer exact tests. Also, haplotypic frequencies were estimated using MLocus software. RESULTS: African-derived HIV-infected individuals presented a higher frequency of the 14 bp insertion allele as compared to non-infected individuals (0.468 versus 0.373, respectively; p(Bonf) = 0.010). A higher frequency of the 14 bp insertion +3142G (insG) haplotype (0.456 versus 0.346, p<0.001) and the insG/insG diplotype (OR=1.88, 95%CI = 1.08-3.23, p=0.021) was observed among African-derived patients as compared to uninfected controls. Also, we observed a higher frequency of the ins/ins genotype among African-derived HIV patients co-infected with HCV (OR=2.78, 95%CI = 1.20-6.49, p = 0.008). CONCLUSIONS: Our data point out to an increased frequency of alleles and genotypes associated with low HLA-G expression among African-derived patients, suggesting a potential role for HLA-G in the susceptibility to HIV-1 infection and HCV co-infection in those individuals.

The role of mannose-binding lectin gene polymorphisms in susceptibility to HIV-1 infection in Southern Brazilian patients.

OBJECTIVE: This study investigates the role of mannose-binding lectin (MBL) in the susceptibility to HIV-1 infection analyzing polymorphisms located at the MBL2 promoter and exon 1 regions. MATERIALS AND METHODS: The prevalence of MBL2 variant alleles was investigated in 410 HIV-1-infected patients from the South Brazilian HIV cohort and in 345 unexposed uninfected healthy individuals. The promoter variants were genotyped using polymerase chain reaction with sequence-specific primers (PCR-SSP) and exon 1 variants were analyzed by real-time PCR using a melting temperature assay and were confirmed by PCR-restriction fragment length polymorphism (RFLP). MBL2 genotypic and allelic frequencies were compared between HIV-1-infected patients and controls using the chi-squared tests. RESULTS: The analyses were performed subdividing the individuals according to their ethnic origin. Among Euro-derived individuals a higher frequency of the LX/LX genotype was observed in patients when compared to controls (P < 0.001). The haplotypic analysis also showed a higher frequency of the haplotypes associated with lower MBL levels among HIV-1-infected patients (P = 0.0001). Among Afro-derived individuals the frequencies of LY/LY and HY/HY genotypes were higher in patients when compared to controls (P = 0.009 and P = 0.02). CONCLUSIONS: An increased frequency of MBL2 genotypes associated with low MBL levels was observed in Euro-derived patients, suggesting a potential role for MBL in the susceptibility to HIV-1 infection in Euro-derived individuals.

Dyslipidemia in HIV-infected individuals

Metabolic complications continue to play a major role in the management of HIV infection. Dyslipidemia associated with HIV infection and with the use of combined antiretroviral therapy includes elevations in triglycerides, reduced high-density cholesterol, and variable increases in low-density and total cholesterol. The association between dyslipidemia and specific antiretroviral agents has been underscored. Multiple pathogenic mechanisms by which HIV and antiretroviral agents lead to dyslipidemia have been hypothesized, but they are still controversial. The potential clinical and pathological consequences of HIV-associated hyperlipidemia are not completely known, but several studies reported an increased risk of coronary artery disease in HIV-positive individuals receiving combined antiretroviral therapy. HIV-infected persons who have hyperlipidemia should be managed similarly to those without HIV infection in accordance with the National Cholesterol Education Program. Life style changes are the primary target. Statins and fibrates and/or modification in antiretroviral therapy are possible approaches to this problem.

Dyslipidemia in HIV-infected individuals.

Metabolic complications continue to play a major role in the management of HIV infection. Dyslipidemia associated with HIV infection and with the use of combined antiretroviral therapy includes elevations in triglycerides, reduced high-density cholesterol, and variable increases in low-density and total cholesterol. The association between dyslipidemia and specific antiretroviral agents has been underscored. Multiple pathogenic mechanisms by which HIV and antiretroviral agents lead to dyslipidemia have been hypothesized, but they are still controversial. The potential clinical and pathological consequences of HIV-associated hyperlipidemia are not completely known, but several studies reported an increased risk of coronary artery disease in HIV-positive individuals receiving combined antiretroviral therapy. HIV-infected persons who have hyperlipidemia should be managed similarly to those without HIV infection in accordance with the National Cholesterol Education Program. Life style changes are the primary target. Statins and fibrates and/or modification in antiretroviral therapy are possible approaches to this problem.

Síncope vasovagal e suplementação de sal: [revisão] / Vasovagal syncope and salt supplementation: [review]

Síncope é definida como uma perda súbita e breve da consciência e do tônus postural devido à hipoperfusão cerebral. A síncope vasovagal é a causa mais comum de síncope entre todas as etiologias. A incidência pode variar de 21 a 35%, acometendo geralmente pessoas jovens e saudáveis. A fisiopatologia da síncope vasovagal não está completamente esclarecida, contudo, pode ser explicada por vasodilatação e bradicardia reflexo-mediada. Estudos vêm sendo desenvolvidos na tentativa de se encontrar melhores formas de abordagem terapêutica para essa disautonomia, muitas vezes resistente aos tratamentos propostos. Agentes farmacológicos são utilizados, mas a eficácia é questionável e os efeitos adversos são comuns. Até o momento, dispõe-se de poucos estudos randomizados os quais envolvem, na maioria das vezes, pequeno número de pacientes. Medidas terapêuticas têm sido propostas para prevenção de recorrências, como orientações gerais não farmacológicas, reconhecimento dos pródromos e fatores desencadeantes, programas de treinamento fisico e postural, aumento da ingestão hídrica e de sal. Alguns achados sugerem que exista influência da suplementação de sal em parâmetros clínicos da síncope vasovagal. O mecanismo pelo qual a administração de sal previne a síncope não é bem conhecido, embora sua eficácia seja atribuída à expansão de volume extracelular. A suplementação de sal pode aumentar o peso corpóreo, o volume plasmático, a tolerância ortostática e a pressão arterial na posição ortostática. Entretanto, um subgrupo específico de pessoas nas quais os sintomas não são devidamente controlados necessita de intervenção farmacológica e não farmacologia. Em geral, obtêm-se bons resultados terapêuticos com mudanças nos hábitos alimentares e comportamentais.

Syncope is defined as a sudden and brief loss of consciousness and postural tonus due to cerebral hypoperfusion. Vasovagal syncope is the most common cause of syncope among all etiologies. The incidence may range from 21 to 35% and this condition usually affects young, healthy people. Its pathophysiology has not been elucidated yet, and it may due to vasodilation and reflex-mediated bradycardia. Some studies have been carried out as an attempt to find better therapeutic approaches for this dysautonomy which is often resistant to the treatments suggested. Pharmacological agents have been used, but the efficacy has not been fully proven and adverse effects are common. Currently, there are few randomized studies and most of them involve small samples. Therapeutic measures have been suggested to prevent relapses, including general non-pharmacological approaches such as recognizing the symptoms and the triggering factors, programs of physical and postural training, increase in the water and salt intake. Some findings suggest there is an influence of salt supplementation in the clinical parameters of vasovagal syncope. The mechanism that prevents syncope using salt administration has not been completely understood, although its efficacy is attributed to the expansion of the extracellular volume. Salt supplementation can increase body weight, plasma volume, orthostatic tolerance and blood pressure in the upright posture. However, a specific subgroup of people who presents with symptoms that are not appropriately controlled need intervention pharmacological and non pharmacology. In general, good therapeutic results are achieved with changes in diet and behavior.