Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection.

The Human papillomavirus is responsible for the most common sexually transmitted infection and is also known to be an oncogenic virus that is associated with cervical, anogenital, and head-neck cancers. The present study aims to assess whether oxidative DNA damage is correlated with the grade of HPV-related lesions. Moreover, we evaluated clinical data and unhealthy lifestyles to verify their possible influence on the genesis of oxidative DNA damage in cervical cells. We quantified the amount of 8-Oxo-2'-deoxyguanosine in DNA as a biomarker of oxidative damage in women with and without HPV infection. We also correlated oxidative damage with different stages of cervical lesions and available clinical data (e.g., HPV genotypes). To identify HPV infections, in which proteins with a transforming potential are produced, we performed a qualitative detection of HPV E6/E7 mRNA. Our results showed greater oxidative damage in HPV-related dysplastic cervical lesions compared to samples with normal cytology, especially in women with high-grade squamous intraepithelial lesions. The latter showed a closed link with high-risk HPV genotypes. Reactive oxygen species can induce DNA double-strand breaks in both the host DNA and in the circular viral episome; this could facilitate the integration of the virus, promoting HPV carcinogenesis. Therefore, in HPV-infected women, it could be useful to reduce additional resources of reactive oxygen/nitrogen species (RONS) with a healthy lifestyle.

Human papillomavirus types distribution in eastern Sicilian females with cervical lesions. A correlation with colposcopic and histological findings.

To determine human papillomavirus (HPV) types distribution in cervical lesions in a Southern Italian female population in Messina and their relationship between HPV type and grade of colposcopic and histopathological abnormality, a total of 253 women aged 17-68 years, with previous cytological abnormalities, were included in this study. HPV-DNA testing, colposcopy and biopsy were performed. For each sample, cervical cells were collected by centrifugation and DNA was extracted, followed by a PCR-based HPV-DNA assay and reverse dot blot genotyping. HPV-16 was found the most common type (46.6 %) followed by HPV-31 (26.9 %), -6 (18.6 %), -58 (8.8 %), -18 (6.7 %), -66 (5.7 %), -52 and -53 (4.7 %). Out of 62 women with abnormal transformation zone (ATZ) area compatible with squamous intraepithelial lesion (SIL) or cervical cancer (CC), 64.5 % was found high risk (HR) HPV-positive. Moreover the severity of the colposcopic diagnosis was positively correlated with the higher HPV oncogenicity risk (HPV-16 P = 0.023; and HPV-53 P = 0.047). The HPV-16 was found the most prevalent type within each histological category: 66.7 %, 31.2 %, 44 % and 37.2 % of CC, high grade (H)SIL, low grade (L)SIL and chronic cervicitis respectively; followed by HPV-31 present in 25 %, 8 %, and 13.3 % of HSIL, LSIL and chronic cervicitis respectively. A higher HPV incidence than the rest of Italy was found, in agreement with that detected by other authors for the South of the country. These data provide further information about the types prevalence in women with cervical lesions living in Eastern Sicily, suggesting the introduction of new targeted vaccines against a wider spectrum of HPV.

myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study.

OBJECTIVE: To check the hypothesis that myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) onset in pregnant women with a family history of type 2 diabetes. RESEARCH DESIGN AND METHODS: A 2-year, prospective, randomized, open-label, placebo-controlled study was carried out in pregnant outpatients with a parent with type 2 diabetes who were treated from the end of the first trimester with 2 g myo-inositol plus 200 µg folic acid twice a day (n = 110) and in the placebo group (n = 110), who were only treated with 200 µg folic acid twice a day. The main outcome measure was the incidence of GDM in both groups. Secondary outcome measures were as follows: the incidence of fetal macrosomia (>4,000 g), gestational hypertension, preterm delivery, caesarean section, shoulder dystocia, neonatal hypoglycemia, and neonatal distress respiratory syndrome. GDM diagnosis was performed according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations. RESULTS: Incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group: 6 vs. 15.3%, respectively (P = 0.04). In the myo-inositol group, a reduction of GDM risk occurrence was highlighted (odds ratio 0.35). A statistically significant reduction of fetal macrosomia in the myo-inositol group was also highlighted together with a significant reduction in mean fetal weight at delivery. In the other secondary outcome measures, there were no differences between groups. CONCLUSIONS: myo-Inositol supplementation in pregnant women with a family history of type 2 diabetes may reduce GDM incidence and the delivery of macrosomia fetuses.

The effect of vaginally administered genistein in comparison with hyaluronic acid on atrophic epithelium in postmenopause.

PURPOSE: The quality of life in postmenopause is seriously affected by the symptoms related to vaginal atrophy. To evaluate in a 3-month, prospective, randomized, double blind, study whether vaginal suppositories containing genistein might improve genital symptoms, colposcopical and cytologic findings or modify DNA cytometric features in postmenopausal women affected by vaginal atrophy, in comparison with vaginal suppositories containing hyaluronic acid (HA). METHODS: A total of 62 postmenopausal women were randomly assigned to receive intravaginally 97 µg of genistein (group A, n = 31) or 5 mg of HA (group B, n = 31) daily for 15 days continuously/month for 3 months. Vaginal and cervical smear, colposcopy, vaginal biopsy were performed before and at the end of the study. Maturation value (MV) was calculated. Flow cytometric analysis of DNA ploidy (DI) and S-phase fraction (SPF) were performed. RESULTS: After 90 days of study, a significant improvement was obtained in genital symptoms, colposcopy scores and MV (p < 0.001) in both groups; the improvement obtained by genistein was more effective especially regarding genital score (p value between groups 0.001). No significant change was found in SPF value and DI. CONCLUSION: Both treatments improved genital symptoms, colposcopical features and MV, although genistein was more effective on genital score. Both treatments did not significantly influence flow cytometry parameters, although genistein showed slight decrease in DI, with a normalization of the aneuploid content present in some cases that could represent an additional application of intravaginal phytoestrogen therapy, providing an alternative therapy of vaginal atrophy in postmenopausal patients. The results of this investigation should be considered preliminary and need to be verified in larger, prospective studies.

Detection and genotyping of human papillomavirus in gynaecologic outpatients of Messina, eastern Sicily, Italy.

In order to determine the prevalence of human papillomavirus (HPV) infection in sexually active female population in Messina, we tested cervical scrapes of women referred to university clinics for routine gynaecologic care. Between March and December 2008, a total of 680 cervical samples of 598 patients (573 Italian from province of Messina and 25 resident aliens) were examined consecutively from laboratory of molecular biology at the Department of Human Pathology. For each sample, cervical cells were collected by centrifugation and DNA was extracted (QIAamp DNA mini kit, Qiagen), followed by a PCR-based HPV DNA assay and reverse dot blot genotyping (HPV-HS Bio plus HPV-strip, AB Analytica or HPV-type, AB Analytica). The overall rate of HPV DNA detection in Italian patients (mean age 34 years; range 15-69) was 70.5% (404/573), with 163 cases of multiple infections (40.3%). In 335 patients (82.9%) a high-risk HPV infection was detected. In this group the coexistence of a low-risk HPV infection was documented in 97 cases while 65 patients exhibited only a low-risk HPV infection. HPV-16 was the most prevalent (33.4%), followed by HPV-6 (28.0%), HPV-31 (24.3%), HPV-58 (11.4%), HPV-66 (11.1%), HPV-53 (6.4%), HPV-18 (6.2%), HPV-56 (5.4%), HPV-33 (5.2%) while the other genotypes identified (HPV-11, -40, -42, -43, -44, -54, -61, -70, -81, -26, -35, -39, -45, -51, -52, -59, -68, -73, -82) were below 5%. HPV prevalence (any type) was 78.7% at age < or =24 years, 73.4% at 25-34 years and 67.1% at 35-44 years and 58.1% at age > or =45 years. A significant association (chi2=12.718; P=0.006) between HPV DNA detection and the younger age was encountered. Since available data on the prevalence and distribution of HPV infection in Italy are somewhat discordant, this study represents a helpful contribution to the knowledge on the circulation of precise genotypes in east Sicily in order to improve new HPV vaccines.