Synergic effect of oral contraceptives, GSTP1 polymorphisms, and high-risk HPV infection in development of cervical lesions.

Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control. Our data did not show a significant association between the GSTP1 polymorphism A/G (rs1695) and any HPV-related cervical abnormalities. However, considering the use of oral contraceptives, the GSTP1 rs1695 polymorphism was associated with higher susceptibility to the development of cervical lesions in HR-HPV-infected women. Our study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions. Together, these risk factors may induce neoplastic transformation of the cervical squamous epithelium, setting conditions for secondary genetic events leading to cervical cancer.

Prevalence of human papillomavirus (HPV), distribution of HPV types, and risk factors for infection in HPV-positive women.

The aim of this study was to describe the prevalence of human papillomavirus (HPV), the distribution of different HPV types, and the putative risk factors for infection among HPV-positive women from the State of Alagoas, Northeast Brazil. We analyzed data from 515 patients attending public and private health centers. HPV DNA from cervical samples was extracted and HPV genotyping was performed by polymerase chain reaction using MY09/11 consensus primers followed by direct sequencing. The chi-squared test for independence was used to assess statistical differences between the HPV groups. HPV DNA was found in 111 (21.55%) cervical samples. Twenty genotypes were detected: HPV6, 11, 16, 31, 33, 35, 39, 52, 53, 54, 58, 61, 62, 66, 70, 72, 81, 82, 83, and 84. In addition, multiple sexual partners (P = 0.002) and the use of oral contraceptives (P = 0.015) were associated with the presence of HPV. These findings may be relevant to the design of screening and vaccination strategies targeting specific groups of women in Northeast Brazil.

Putative Mechanisms of Viral Transmission and Molecular Dysregulation of Mammary Epithelial Cells by Human Papillomavirus: Implications for Breast Cancer.

Breast cancer is the most common cancer in women worldwide. Several studies have demonstrated the presence of Human papillomavirus (HPV) DNA in breast cancer samples. However, the role of HPV in breast carcinogenesis is not clear, and the interaction mechanisms between this infectious agent and the breast cancer cell need to be more fully clarified. In this article, we discuss the putative roles of HPV infection in breast carcinogenesis.

Bovine papillomavirus E2 and E5 gene expression in sperm cells of healthy bulls.

Papillomaviruses are found in epithelial lesions and are linked to different carcinogenic processes in humans and other animals. Although BPV has been characterized as epitheliotropic, the presence of viral DNA has been detected in other tissues and fluids, such as fresh semen. The aim of this study was to evaluate the presence and expression of BPV in sperm cells of bulls (Bos taurus) asymptomatic for papillomatosis. A PCR assay was carried out with specific primers to test BPV2 in 26 semen samples. The presence of BPV transcripts was assessed by RT-PCR to E2 and E5 genes. BPV2 DNA was detected in nine out of 26 samples and the expression of E2 and E5 were detected in five out of nine BPV positive samples. This is the first record of BPV2 expression in bull sperm cells.

Avaliação da toxicidade aguda do extrato das cascas de Pithecellobium cochliocarpum (Gomez) Macbr / Evaluation of acute toxicity of the Pithecellobium cochliocarpum (Gomez) Macbr bark extract

O uso popular, e mesmo o tradicional, não são suficientes para validar as plantas medicinais como medicamentos eficazes e seguros. Para melhor entendimento, é necessário avaliar a relação risco/benefício de seu uso, por meio de estudos toxicológicos. O objetivo desta pesquisa foi estimar a toxicidade aguda do extrato etanólico das cascas secas de Pithecellobium cochliocarpum (Gomez) Macbr através da obtenção da dose letal (DL50) em roedores, e da Concentração letal (CL50) frente à Artemia salina Leach. Foram realizados experimentos por via oral e intraperitoneal utilizando camundongos fêmeas albinos Swiss (Mus musculus) (n=6). Por via oral foram administradas 3 doses (1.000, 3.000 e 5.000 mg Kg-1) e por via entraperitoneal, 5 doses (155, 160, 176, 345,6 e 414,72 Kg-1). Os sinais comportamentais foram avaliados durante uma hora após a administração do extrato, ficando em observação até 48 horas. O número de óbitos foi quantificado para posterior cálculo da DL50. A administração por via intraperitoneal foi realizada em intervalo de 5 minutos para cada animal. Nos ensaios de toxicidade por via oral a solução foi introduzida por via intragástrica através de cânula metálica acoplada a seringa (gavagem) no mesmo intervalo de tempo utilizado pela via intraperitoneal. Os animais do grupo de administração oral apresentaram algumas reações, porém não letais até a dose de 5.000 mg Kg-1. A DL50 para a via intraperitoneal foi 257, 49 mg Kg-1 (muito tóxico, grau 4) (Schuartsman, 1980). A CL50 (543,5 µg Kg-1) demonstrou ser tóxica frente à A. salina. Conclui-se que sob condições agudas de exposição, o extrato do Pithecellobium cochliocarpum é um agente tóxico, devendo ser considerado como tal, dependendo da dose administrada ou absorvida, do etempo e frequência de exposição e das vias de administração.

The popular use, and even the traditional one, is not enough to validate medicinal plants as effective and safe medicines. For a better understanding, it is necessary to assess the risk / benefit ratio of their use through toxicological studies. The aim of this work was to evaluate the acute toxicity of Pithecellobium cochliocarpum (Gomez) Macbr dried bark ethanolic extract through its lethal dose (LD50), in mice, and lethal concentration (LC50) in relation to Artemia salina Leach. Experiments were performed by oral and intraperitoneal route using female Swiss albino mice (Mus musculus) (n = 6). The first three doses were given orally (1,000, 3,000 and 5,000 mg kg-1) and the last five doses were given intraperitoneally (155, 160, 176, 345.6 and 414.72 Kg-1). The behavioral signs were evaluated one hour after administration of the extract, being observed up to 48 hours. The number of deaths was quantified for subsequent calculation of LD50. The intraperitoneal administration was carried out at an interval of 5 minutes for each animal. For the oral toxicity test, the solution was introduced in the digestive system of the animals through a metal cannula coupled to a syringe (gavage) at the same time interval used for the intraperitoneal route. The animals from the oral group presented some reactions, but they were not lethal up to the dose of 5.000 mg kg-1. The LD50 for the intraperitoneal group was 257.49 mg kg-1 (very toxic, grade 4) (Schuartsman, 1980). The LC50 (543.5 mg kg-1) was toxic to A. salina. We can conclude that, under acute conditions of exposure, the Pithecellobium cochliocarpum extract is a poisonous agent and should be considered as such depending on the administered or absorbed dose, the time and frequency of exposure, and the administration routes.