Detecção de receptor de ácido hialurônico em prega vocal humana por método imunohistoquímico

O receptor do ácido Hialurônico é uma glicoproteína da membrana plasmática, sendo o principal o CD44, e está expresso em vários tipos de células onde possui a função de adesão celular. OBJETIVO: Estudar a possibilidade de empregar o método imunohistoquímico para identificar a distribuição dos receptores de ácido hialurônico ao longo da prega vocal humana. MATERIAL E MÉTODOS: Foram ressecadas as pregas vocais normais de um indivíduo de 23 anos, sexo masculino, cor negra. As lâminas foram analisadas por meio de estudo histomorfométrico, comparando-se a intensidade das cores nas camadas superficial, média e profunda da lâmina própria. Nas lâminas silanizadas foi utilizado método imunohistoquímico, sendo avaliadas através de microscopia óptica com aumento 40 vezes, obtendo coloração marrom onde houve a reação com receptor para ácido hialurônico. RESULTADOS: Os achados imunohistoquímicos mostraram presença de receptores para ácido hialurônico no epitélio de cobertura da prega vocal tendo maior concentração na região central da prega vocal. CONCLUSÃO: A técnica de imunohistoquímica, utilizada para avaliar a distribuição dos receptores para ácido hialurônico na pregas vocais humanas, mostrou sua disposição em epitélio da prega vocal e predomínio no terço médio, em relação às demais regiões na prega vocal estudada.

Seroprevalence of hepatitis B virus infection in individuals with clinical evidence of hepatitis in Goiânia, Goiás: detection of viral DNA and determination of subtypes

The presence of serological markers for hepatitis B virus (HBsAg, anti-HBc IgM and Anti-HBc total) was investigated in the serum of 1,396 individuals who had clinical suspect of hepatitis. It was observed that 50.7% of the individuals were positive and, from the total of the studied individuals, 14.5% were positive for HBsAg. From these, 8.5% were also positive for anti-HBc IgM. The analysis in relation to gender showed a higher seroprevalence index among male individuals (p < 0.0001). It was observed the occurrence of subtypes adw2 (62.7%), ayw3 (23.5%), ayw2 (9.8%) and adw4 (3.9%). The viral DNA was detected in 61 (33.9%) HBsAg positive samples and in one sample positive only for anti-HBc total. These results indicate an important incidence of the HBV infection in this population, and reinforce previous studies regarding this virus in the central west region of Brazil.

Seroprevalence of antibodies to Venezuelan equine encephalitis complex (subtypes IAB and VI) in humans from General Belgrano Island, Formosa, Argentina

This work presents the results of the detection of antibodies (immunoglobulin G) for subtypes I and VI of VEE viruses complex (Togaviridae family) in people from the General Belgrano island, Formosa province (Argentina). The prevalence of neutralizing (NT) antibodies for subtype VI was from 30% to 70% and the prevalence of antibodies inhibitory of hemagglutination (HI) was of 0% in the first and second inquiry respectively. For the subtype IAB the prevalence of NT antibodies was from 13% to 3.6%, similar to the prevalence total for both subtypes. HI antibodies were not detected in any inquiries for any subtype. It was observed that both subtypes circulate simultaneously, while subtype VI remains constant with some peaks, subtype I was found in low level.

Mother-to-child transmission of different HIV-1 subtypes among ARV Naïve infected pregnant women in Nigeria

The rate of mother-to-child transmission (MTCT) of HIV as well as the implications of the circulating multiple subtypes to MTCT in Nigeria are not known. This study was therefore undertaken to determine the differential rates of MTCT of HIV-1 subtypes detected among infected pregnant women before ARV intervention therapy became available in Nigeria. Twenty of the HIV-positive women who signed the informed consent form during pregnancy brought their babies for follow-up testing at age 18-24 months. Plasma samples from both mother and baby were tested for HIV antibody at the Department of Virology, UCH, Ibadan, Nigeria. All positive samples (plasma and peripheral blood mononuclear cells - PBMCs) were shipped to the Institute of Tropical Medicine, Antwerp, Belgium, where the subtype of the infecting virus was determined using the HMA technique. Overall, a mother-to-child HIV transmission rate of 45% was found in this cohort. Specifically, 36.4%, 66.7% and 100% of the women infected with HIV-1 CRF02 (IbNg), G and B, respectively, transmitted the virus to their babies. As far as it can be ascertained, this is the first report on the rate of MTCT of HIV in Nigeria. The findings reported in this paper will form a useful reference for assessment of currently available therapeutic intervention of MTCT in the country.

THE INFLUENCE OF HIV-1 SUBTYPES C, CRF31_BC AND B ON DISEASE PROGRESSION AND INITIAL VIROLOGIC RESPONSE TO HAART IN A SOUTHERN BRAZILIAN COHORT

Background: Although most HIV-1 infections in Brazil are due to subtype B, Southern Brazil has a high prevalence of subtype C and recombinant forms, such as CRF31_BC. This study assessed the impact of viral diversity on clinical progression in a cohort of newly diagnosed HIV-positive patients. Methods: From July/2004 to December/2005, 135 HIV-infected patients were recruited. The partial pol region was subtyped by phylogeny. A generalized estimating equation (GEE) model was used to examine the relationship between viral subtype, CD4+ T cell count and viral load levels before antiretroviral therapy. Hazard ratio (Cox regression) was used to evaluate factors associated with viral suppression (viral load < 50 copies/mL at six months). Results: Main HIV-1 subtypes included B (29.4%), C (28.2%), and CRF31_BC (23.5%). Subtypes B and C showed a similar trend in CD4+ T cell decline. Comparison of non-B (C and CRF31_BC) and B subtypes revealed no significant difference in the proportion of patients with viral suppression at six months (week 24). Higher CD4+ T cell count and lower viral load were independently associated with viral suppression. Conclusion: No significant differences were found between subtypes; however, lower viral load and higher CD4+ T cell count before therapy were associated with better response.

Avaliação da expressão de interleucina 1 beta (IL-1β) e antagonista do receptor de interleucina 1 (IL-1Ra) em pacientes com hanseníase

A hanseníase é uma doença infectocontagiosa espectral que acompanha-se por uma série de eventos imunológicos desencadeados pela resposta do hospedeiro frente ao agente etiológico, o Mycobacterium leprae. Evidências sugerem que a indução e manutenção da resposta imune/inflamatória na hanseníase estão vinculadas a interações de múltiplas células e fatores solúveis, particularmente através da ação de citocinas. Nesse estudo, foram mensurados níveis de IL-1β e IL-1Ra de 37 casos novos de hanseníase acompanhados ao longo do tratamento e 30 controles sadios pelo teste ELISA. A coleta de sangue periférico foi realizada em quatro tempos para os casos de hanseníase (pré-tratamento com PQT, 2ª dose, 6ª dose e pós-PQT) e em único momento para os controles. Na comparação dos níveis das moléculas de casos no pré-PQT e controles, houve diferença estatisticamente significativa somente para IL-1β. Nossos resultados sugerem a participação dessa citocina no processo imune/inflamatório.

Abnormal spontaneous interleukin 8 receptor expression: a brief report of two cases

Interleukin 8 (CXCL8) is an autocrine chemokine specific for the chemoattraction and activation of granulocytes, NKT cells and T lymphocytes. Patients with tuberculosis and latent Mycobacterium tuberculosis infection were assessed for the spontaneous expression of CXCR1 (CD128) and CXCR2 on lymphocytes and monocytes. Compared with ex vivo profiles, increased spontaneous CXCR2 expression and normal CXCR1 expression were found on lymphocytes in two out of 59 individuals. Monocytes showed normal ex vivo profiles for both receptors. After stimulation with purified protein derivative, the in vitro levels of CXCL8 were below the median levels of all patients with prior tuberculosis. Spontaneous CXCR2 modulation did not cause notable variation in the in vitro levels of CXCL8.

Glucocorticoid-induced tumor necrosis factor receptor expression in patients with cervical human papillomavirus infection

Introduction The progression of human papillomavirus (HPV) infection in the anogenital tract has been associated with the involvement of cells with regulatory properties. Evidence has shown that glucocorticoid-induced tumor necrosis factor receptor (GITR) is an important surface molecule for the characterization of these cells and proposes that GITR ligand may constitute a rational treatment for many cancer types. We aimed to detect the presence of GITR and CD25 in cervical stroma cells with and without pathological changes or HPV infection to better understand the immune response in the infected tissue microenvironment. Methods We subjected 49 paraffin-embedded cervical tissue samples to HPV DNA detection and histopathological analysis, and subsequently immunohistochemistry to detect GITR and CD25 in lymphocytes. Results We observed that 76.9% of all samples with high GITR expression were HPV-positive regardless of histopathological findings. High GITR expression (77.8%) was predominant in samples with ≥1,000 RLU/PCB. Of the HPV-positive samples negative for intraepithelial lesion and malignancy, 62.5% had high GITR expression. High GITR expression was observed in both carcinoma and high-grade squamous intraepithelial lesion (HSIL) samples (p = 0.16). CD25 was present in great quantities in all samples. Conclusions The predominance of high GITR expression in samples with high viral load that were classified as HSIL and carcinoma suggests that GITR+ cells can exhibit regulatory properties and may contribute to the progression of HPV-induced cervical neoplasia, emphasizing the importance of GITR as a potential target for immune therapy of cervical cancer and as a disease evolution biomarker.

Toll-like receptor 3 gene polymorphisms are not associated with the risk of hepatitis B and hepatitis C virus infection

INTRODUCTION: The present study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: Samples collected from HCV (n = 74) and HBV (n = 35) carriers were subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and prothrombin time (PT). A healthy control group was investigated and consisted of 299 HCV- and HBV-seronegative individuals. RESULTS: No significant differences in allele, genotype and haplotype frequencies were observed between the investigated groups, and no association was observed between the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305; p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels. CONCLUSIONS: This genetic analysis revealed the absence of an association between the polymorphisms investigated and susceptibility to HBV and HCV infection; however, these polymorphisms might be associated with a greater degree of biliary damage during the course of HCV infection.

HIV-1 epidemiology and circulating subtypes in the countryside of South Brazil

INTRODUCTION: Human immunodeficiency virus type 1 (HIV-1) has spread worldwide, with several subtypes and circulating recombinant forms. Brazil has an incidence of 20.5 HIV-1/acquired immunodeficiency syndrome (AIDS) patients per 100,000 inhabitants; however, the Southernmost State of Rio Grande do Sul (RS) has more than twice the number of HIV-1-infected people (41.3/100,000 inhabitants) and a different pattern of subtype frequencies, as previously reported in studies conducted in the capital (Porto Alegre) and its metropolitan region. This study examined HIV-1/AIDS epidemiological and molecular aspects in the countryside of Rio Grande do Sul. METHODS: Socio-demographic, clinical and risk behavioral characteristics were obtained from HIV-1-positive adult patients using a structured questionnaire. HIV-1 subtypes were determined by nested-polymerase chain reaction (PCR) and sequencing of the pol and env genes. RESULTS: The study sample included 149 (55% women) patients with a mean age of 41.8 ± 11.9 years. Most (73.8%) patients had a low education level and reported heterosexual practices as the most (91.9%) probable transmission route. HIV-1 subtypes were detected in 26 patients: 18 (69.2%) infected with subtype C, six (23.1%) infected with subtype B and two (7.7%) infected with BC recombinant forms. CONCLUSIONS: These data highlight the increasing number of HIV-1 subtype C infections in the countryside of South Brazil.

Effect of arginine vasopressin on the canine epicardial coronary artery: experiments on V1-receptor-mediated production of nitric oxide

OBJECTIVE: To determine whether arginine vasopressin releases endothelium-derived nitric oxide (EDNO) from the epicardial coronary artery. METHODS: We studied segments of canine left circumflex coronary arteries suspended in organ chambers to measure isometric force. The coronary artery segments were contracted with prostaglandin F2alpha (2 x 10-6M) and exposed to a unique, strong arginine vasopressin concentration (10-6M) or titrated concentrations (10-9 a 10-5 M). RESULTS: The unique dose of arginine vasopressin concentration (10-6M) induced transient, but significant (p<0.05), relaxation in arterial segments with endothelium, and an increase, not significant, in tension in arteries without endothelium. Endothelium-dependent relaxation to arginine vasopressin was inhibited by Ng-monomethyl-L-arginine (L-NMMA, 10-5M) or N G-nitro-L-arginine (L-NOARG) (10-4M), 2 inhibitors of nitric oxide synthesis from L-arginine. Exogenous L-arginine (10-4M), but not D-arginine (10-4M), reversed the inhibitory effect of L-NMMA on vasopressin-mediated vasorelaxation. Endothelium dependent relaxation to vasopressin was also reversibly inhibited by the vasopressin V1-receptor blocker d(CH2)5Try(Me) arginine vasopressin (10-6M) (n=6, P<0.05). CONCLUSION: Vasopressin acts through V1 endothelial receptors to stimulate nitric oxide release from L-arginine.

O polimorfismo A1166C do receptor tipo 1 da angiotensina II no infarto agudo do miocárdio

RESUMO OBJETIVO:Avaliar a associação do polimorfismo A1166C do gene do receptor AT1 da angiotensina II (AT1R) com o infarto agudo do miocárdio e a severidade da doença arterial coronariana. MÉTODOS: Estudo prospectivo, transversal de 110 pacientes com infarto agudo do miocárdio submetidos à angiografia coronariana com lesão significante (> 50%) avaliada por três critérios de severidade: número de vasos lesados, morfologia da placa aterosclerótica e escore de risco coronariano. Sem lesões coronarianas 104 indivíduos controles. O polimorfismo A1166C do gene do AT1R foi determinado pela reação em cadeia da polimerase no DNA dos leucócitos do sangue periférico. Os fatores de risco coronariano clássicos foram analisados em todos os indivíduos. RESULTADOS: Na estratificação dos genótipos em relação aos fatores de risco apenas o tabagismo teve predominância nos heterozigotos AC (p = 0,02). A freqüência dos genótipos nos pacientes infartados foi de AA = 54,5%; AC = 35,5% e CC = 10%, sendo similar e não significativa em relação aos controles (p = 0,83). Não houve aumento do risco de infarto agudo do miocárdio nas comparações dos genótipos CC vs AA (OR = 1,35; IC-95% = 0,50 - 3,59), AC vs AA (OR = 1,03; IC-95% = 0,58 - 1,84 e AA+AC vs AA (OR = 1,33; IC-95% = 0,51 - 3,45). Nenhum dos critérios de severidade teve associação significativa com os genótipos. CONCLUSÃO: Os nossos resultados indicam não haver associação do polimorfismo A1166C do AT1R com o infarto agudo do miocárdio e nem com a severidade da doença arterial coronariana segundo nossos resultados.

Sildenafil melhora a função ventricular direita no receptor de transplante cardíaco

Relatamos caso de um paciente submetido a transplante cardíaco ortotópico, onde se utilizou um doador marginal pela piora clínica do receptor, que apresentava choque cardiogênico por disfunção de ventrículo direito secundária a hipertensão pulmonar associado à vasoplegia. Obtivemos recuperação hemodinâmica do paciente, com redução da resistência vascular pulmonar, retirada de drogas vasoativas e recuperação da função do ventrículo direito após a introdução de sildenafil.

O polimorfismo VNTR no gene codificador do antagonista do receptor da interleucina-1 está associado com a doença arterial coronariana

FUNDAMENTO: A Doença Arterial Coronariana (DAC) é a aterosclerose das artérias coronárias que transportam o sangue para o coração. A aterosclerose é uma doença inflamatória. As variações gênicas das citocinas - como as associadas à família IL1 - fazem parte da patogênese da aterosclerose. OBJETIVO: O objetivo deste estudo foi determinar a relação entre os polimorfismos da família IL1 (VNTR do IL1RN, posições -511 e +3953 do IL1B) e a DAC na população turca. MÉTODOS: Um total de 427 indivíduos foram submetidos à angiografia coronariana e em seguida divididos da seguinte forma: 170 no grupo controle e 257 no grupo de pacientes com DAC. Os sujeitos com DAC foram divididos em dois subgrupos: 91 no grupo de Doença Coronariana em um único vaso (Single Vessel Disease - SVD) e 166 no grupo Doença Coronariana em múltiplos vasos (Multiple Vessel Disease - MVD). Os genótipos de IL1RN e IL1B (-511, +3953) foram determinados por reação em cadeia da polimerase (RCP), seguida de análise da digestão por enzima de restrição. RESULTADOS: Não foram observadas diferenças significantes nas distribuições de genótipos de IL1RN e IL1B (-511 e +3953) entre os sujeitos com DAC e os controles, ou entre sujeitos com MVD e controles. No entanto, observou-se uma relação significante no genótipo IL1RN 2/2 entre sujeitos portadores de SVD e controles (P= 0,016, x2: 10,289, OR: 2,94IC 95% 1,183 - 7,229). Tampouco foi observada diferença estatisticamente significante nas freqüências dos alelos de IL1RN e IL1B (-511 e +3953) entre os sujeitos com DAC e controles, os sujeitos com MVD e controles, ou ainda os sujeitos SVD e controles. CONCLUSÃO: Não foi observada nenhuma relação na freqüência alélica e nem na distribuição genotípica dos polimorfismos de IL1RN e IL1B entre sujeitos com DAC e grupos controle. No entanto, o genótipo IL1RN 2/2 pode representar um fator de risco para sujeitos com SVD na população turca.