HPV infection as a risk factor for atherosclerosis: A connecting hypothesis.

Atheromatous plaques occurring in large arteries are common and life-threatening lesions. Multiple factors are involved in the pathogenesis of atheromatous plaques, such as hyperlipidaemia and hypercholesterolaemia, high blood pressure and chronic systemic inflammation. Recent findings have suggested that infection with high-risk human papillomavirus (HPV) may increase the risk of developing atheromatous plaques. However, HPV is considered a tissue-specific virus with a strong tropism towards squamous epithelial cells, and the mechanisms whereby it may promote the development of atheromas remain unclear. Here, we propose a connecting hypothesis to explain the possible causative role of HPV on atheroma development. We hypothesize that HPV infection may promote atheroma formation in infected patients by enhancing systemic inflammation or by directly targeting blood vessels via nucleic acids carried by extracellular vesicles such as exosomes. The pro-inflammatory effects of HPV and the release of extracellular vesicles by HPV-transformed cells are well documented in scientific literature. Possible experimental approaches to test this hypothesis are also discussed, especially experiments employing transgenic mice bearing HPV16 transgenes. If correct, this hypothesis would have major implications for the prevention of cardiovascular diseases, especially due to the preventable nature of HPV infection through vaccination.

Female Sex Hormones Influence the Febrile Response Induced by Lipopolysaccharide, Cytokines and Prostaglandins but not by Interleukin-1ß in Rats.

There are differences in the immune response, and particularly fever, between males and females. In the present study, we investigated how the febrile responses induced by lipopolysaccharide (LPS) and different endogenous pyrogens were affected by female gonadal hormones. The febrile response to i.p. injection of LPS (50 µg/kg) was 40% lower in female rats compared to male or ovariectomised (OVX) female rats. Accordingly, oestrogen replacement in OVX animals reduced LPS-induced fever. Treatment with the prostaglandin synthesis inhibitor indomethacin (2 mg/kg, i.p. 30 min before) reduced the febrile response induced by LPS in both OVX (88%) and sham-operated (71%) rats. In line with the enhanced fever in OVX rats, there was increased expression of cyclooxygenase-2 (COX-2) in the hypothalamus and elevated levels of prostaglandin E2 (PGE2 ). In addition, OVX rats were hyper-responsive to PGE2 injected i.c.v. By contrast to the enhanced fever in response to LPS and PGE2 , the febrile response induced by i.c.v. injection of interleukin (IL)-1ß was unaffected by ovariectomy, whereas the responses induced by tumour necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-1α were completely abrogated. These results suggest that the mediators involved in the febrile response in females are similar to males, although the reduction of female hormones may decrease the responsiveness of some mediators such as TNF-α and MIP-1α. Compensatory mechanisms may be activated in females after ovariectomy such as an augmented synthesis of COX-2 and PGE2 .

Association between periodontal changes and osteoporosis in postmenopausal women.

OBJECTIVE: To investigate the possible association between periodontal changes and osteoporosis in postmenopausal women through a longitudinal study. METHODS: This longitudinal study included 33 patients. The participants were divided into three groups according to the bone mineral density assessed in the lumbar region: normal bone (G1, n = 15), osteopenia (G2, n = 12) and osteoporosis (G3, n = 6). Periodontal evaluation included clinical attachment level, probing depth, gingival bleeding index and visible plaque index, evaluated by two examiners blinded to systemic bone condition. The statistical process included the t-test for paired samples, with a significance level of 5% to check for changes in periodontal parameters considered at initial and final systemic bone density. RESULTS: The results showed that, after follow-up, there was a significant increase in gingival bleeding index in the group of women who had normal initial bone condition and progressed to osteopenia (after 3 years, 59.89%, p = 0.010) and osteoporosis (after 3 years, 74.37%, p = 0.035). In addition, the group diagnosed with osteopenia at baseline who progressed to osteoporosis after 3 years also showed a significant increase in gingival bleeding index (p < 0.001). CONCLUSIONS: The findings suggest that periodontal changes can be associated with osteoporosis in postmenopausal women.

Molecular detection of human papillomavirus in Brazilian women with cervical intraepithelial neoplasia in a northeast Brazilian city.

We examined the prevalence of human papillomavirus (HPV) infection in Brazilian women with cervical intraepithelial neoplasia. Our goal was to identify the types of HPV and their association with risk factors. This prospective cross-sectional study included 97 samples collected from women aged 14-79 years at the public health units of gynecological care in São Luís, MA, Brazil. HPV detection was performed by nested polymerase chain reaction and sequence analysis. The study patients completed a structured questionnaire to provide information regarding their socio-demographic, clinical, and behavioral status. HPV prevalence was found to be 80.4%, with 17 virus types detected, including HPV 16, 18, 58, 6, and 11. Significant associations between HPV infection and age and frequency of doctor visits were identified. The study findings indicate the significance of age and low frequency of visits to the gynecologist as risk factors for genital HPV infection, suggesting that HPV infection-derived cervical cancer could be prevented through orientation programs for women, which include sex education and information regarding screening tests. We also found an increased prevalence of high-risk HPV serotypes in cervical lesions, which reveals an association between cervical lesions and high-risk HPV.

Determination of CYP2D6 *3, *4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and disease-free survival

The CYP2D6 enzyme is crucial for the metabolism of tamoxifen. The CYP2D6 gene is highly polymorphic, and individuals can be extensive, intermediate, or poor tamoxifen metabolizers. The aim of this study was to determine the frequencies of the CYP2D6 *3, *4, and *10 alleles in women with breast cancer who were treated with tamoxifen and analyze the association of enzyme activity with prognostic factors and disease-free survival. We observed a high frequency of CYP2D6 *10, with an allelic frequency of 0.14 (14.4%). The *3 allele was not present in the studied population, and *4 had an allelic frequency of 0.13 (13.8%). We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant. We also observed a high frequency of CYP2D6 *10, which had not been previously described in this specific population. This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes. These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.

Determination of CYP2D6 *3, *4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and disease-free survival.

The CYP2D6 enzyme is crucial for the metabolism of tamoxifen. The CYP2D6 gene is highly polymorphic, and individuals can be extensive, intermediate, or poor tamoxifen metabolizers. The aim of this study was to determine the frequencies of the CYP2D6 *3, *4, and *10 alleles in women with breast cancer who were treated with tamoxifen and analyze the association of enzyme activity with prognostic factors and disease-free survival. We observed a high frequency of CYP2D6 *10, with an allelic frequency of 0.14 (14.4%). The *3 allele was not present in the studied population, and *4 had an allelic frequency of 0.13 (13.8%). We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant. We also observed a high frequency of CYP2D6 *10, which had not been previously described in this specific population. This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes. These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.

Prevalence and conditions associated with chronic pelvic pain in women from São Luís, Brazil

The objective of the present study was to estimate the prevalence of chronic pelvic pain in the community of São Luís, capital of the State of Maranhão, Northeastern Brazil, and to identify independent conditions associated with it. A cross-sectional study was conducted, including a sample of 1470 women older than 14 years predominantly served by the public health system. The interviews were held in the subject's home by trained interviewers not affiliated with the public health services of the municipality. The homes were visited at random according to the city map and the prevalence of the condition was estimated. To identify the associated conditions, the significant variables (P=0.10) were selected and entered in a multivariate analysis model. Data are reported as odds ratio and 95% confidence interval, with the level of significance set at 0.05. The prevalence of chronic pelvic pain was 19.0%. The independent conditions associated with this diagnosis were: dyspareunia (OR=3.94), premenopausal status (OR=2.95), depressive symptoms (OR=2.33), dysmenorrhea (OR=1.77), smoking (OR=1.72), irregular menstrual flow (OR=1.62), and irritative bladder symptoms (OR=1.90). The prevalence of chronic pelvic pain in Sao Luís is high and is associated with the conditions cited above. Guidelines based on prevention and/or early identification of risk factors may reduce the prevalence of chronic pelvic pain in São Luís, Brazil.

Prevalence and conditions associated with chronic pelvic pain in women from São Luís, Brazil.

The objective of the present study was to estimate the prevalence of chronic pelvic pain in the community of São Luís, capital of the State of Maranhão, Northeastern Brazil, and to identify independent conditions associated with it. A cross-sectional study was conducted, including a sample of 1470 women older than 14 years predominantly served by the public health system. The interviews were held in the subject's home by trained interviewers not affiliated with the public health services of the municipality. The homes were visited at random according to the city map and the prevalence of the condition was estimated. To identify the associated conditions, the significant variables (P=0.10) were selected and entered in a multivariate analysis model. Data are reported as odds ratio and 95% confidence interval, with the level of significance set at 0.05. The prevalence of chronic pelvic pain was 19.0%. The independent conditions associated with this diagnosis were: dyspareunia (OR=3.94), premenopausal status (OR=2.95), depressive symptoms (OR=2.33), dysmenorrhea (OR=1.77), smoking (OR=1.72), irregular menstrual flow (OR=1.62), and irritative bladder symptoms (OR=1.90). The prevalence of chronic pelvic pain in Sao Luís is high and is associated with the conditions cited above. Guidelines based on prevention and/or early identification of risk factors may reduce the prevalence of chronic pelvic pain in São Luís, Brazil.