Paula Inserra

Incidence, Prevalence, and Clearance of Type-Specific Human Papillomavirus Infections: The Young Women’s Health Study

The natural history of type-specific human papillomavirus (HPV) infections was examined in a cohort of 331 women aged 18-35 years who self-referred for routine gynecological care. Participants underwent a gynecological examination at baseline and at approximately 4 and approximately 10 months after baseline. Cervical samples were collected for HPV testing and genotyping at each visit, as was information on reproductive, sexual, and medical histories. The rate of new HPV infections was 2.9% per month; the highest rates were observed for HPV types 16, 39, 84, and 51. Among women who tested negative for HPV at baseline, the cumulative probability of acquiring an oncogenic HPV strain during a 12-month follow-up period was 0.32, compared with 0.18 for nononcogenic strains. Women who had had >/=1 new male sex partner in the recent past were significantly more likely to acquire a new HPV infection (relative hazard, 2.39; 95% confidence interval, 1.20-4.76). The median time to clearance of infection was significantly longer for oncogenic strains (9.8 months) than for nononcogenic strains (4.3 months).

Clearance of oncogenic human papillomavirus (HPV) infection: effect of smoking (United States)

Objective: The purpose of this investigation was to assess the association between smoking and clearance of oncogenic human papillomavirus (HPV) infection. Methods: A prospective cohort study of 346 women aged 18–35 years was conducted. HPV testing was conducted with the Hybrid Capture II (HC II) system and polymerase chain reaction (PCR) with genotyping using the reverse line blot method. At each visit tobacco exposure, reproductive, and sexual histories were assessed. Probability of clearing an oncogenic HPV infection and duration of oncogenic HPV infections by smoking status was assessed. Results: Regardless of method used, HC II or PCR, ever smokers maintained an HPV infection significantly longer (median duration of 8.5 months vs 10.7 months, never vs ever smokers), and had a lower probability of clearing an oncogenic infection compared with women who never smoked. Smoking duration was significantly associated with HPV clearance, and a dose response was observed. Older age (> 13 years) at smoking initiation was significantly associated with a reduced probability of clearing an oncogenic HPV infection. Conclusion: This is the first study to demonstrate that smoking promotes early cervical carcinogenic events by increasing duration of oncogenic HPV infections and decreasing probability of clearing oncogenic infections.

Prevention of immune dysfunction and vitamin E loss by dehydroepiandrosterone and melatonin supplementation during murine retrovirus infection

Female C57BL/6 mice infected with the LP‐BM5 leukaemia retrovirus developed murine acquired immune‐deficiency syndrome (AIDS). Dehydroepiandrosterone (DHEA) and melatonin (MLT) modify immune dysfunction and prevent lipid peroxidation. We investigated whether DHEA and MLT could prevent immune dysfunction, excessive lipid peroxidation, and tissue vitamin E loss induced by retrovirus infection. Retrovirus infection inhibited the release of T helper 1 (Th1) cytokines, stimulated secretion of Th2 cytokines, increased hepatic lipid peroxidation, and induced vitamin E deficiency. Treatment with DHEA or MLT alone, as well as together, largely prevented the reduction of B‐ and T‐cell proliferation as well as of Th1 cytokine secretion caused by retrovirus infection. Supplementation also suppressed the elevated production of Th2 cytokines stimulated by retrovirus infection. DHEA and MLT simultaneously reduced hepatic lipid peroxidation and prevented vitamin E loss. The use of DHEA plus MLT was more effective in preventing retrovirus‐induced immune dysfunction than either DHEA or MLT alone. These results suggest that supplementation with DHEA and MLT may prevent cytokine dysregulation, lipid oxidation and tissue vitamin E loss induced by retrovirus infection. Similarly, hormone supplementation also modified immune function and increased tissue vitamin E levels in uninfected mice.

Modulation of Cytokine Production by Dehydroepiandrosterone (DHEA) Plus Melatonin (MLT) Supplementation of Old Mice

Abstract Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone (DHEA) decline with age, and this decline is correlated with immune dysfunction. The aim of the current study is to determine whether hormone supplementation with MLT and DHEA together would synergize to reverse immune senescence. Old (16.5 months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As expected, splenocytes were significantly (P < 0.05) higher in old mice as compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005) increased B cell proliferation in young mice. However, only MLT and DHEA + MLT significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT, and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-γ or significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1 cytokine and elevated Th2 cytokine production; however, their combined use produced only a limited additive effect.

Supplementation with fruit and vegetable extracts may decrease DNA damage in the peripheral lymphocytes of an elderly population

Abstract Fruit and vegetable consumption has been heralded for its ability to decrease the overall risk of developing cancer and other diseases. Mounting evidence supports the beneficial nature of antioxidants, carotenoids, and other phytonutrients found in fruits and vegetables. One proposed mechanism of antioxidant protection is the shielding of cellular DNA from oxidative damage and therefore mutations. This may be especially helpful in older populations. We tested the concept that a daily regimen of supplementation with fruit and vegetable extracts (JuicePlus™) would reduce the amount of DNA damage in the peripheral lymphocytes of the elderly. In a blind study, a group of twenty elderly volunteers (mean age=68) were given supplements twice daily for 80 days with blood samples drawn before and after intervention. These samples were compared using the comet assay, a technique that quantifies DNA damage to individual nuclei. Each sample was tested in triplicate, and tail moment data was collected from over 200 comets per sample. Paired t-test analysis revealed a highly significant (p

Melatonin, Immune Modulation and Aging

Melatonin is a hormone secreted by the pineal gland in response to photoperiods and influences many important biological processes. For one, Melatonin has been shown to produce resistance to cancer and infectious diseases in aged animals. Studies in animals have demonstrated melatonin-related mechanisms of action on immunoregulation. Additionally, melatonin has been successfully used in humans, along with interleukin-2, as a treatment of solid tumors. In vivo and in vitro studies show melatonin enhances both natural and acquired immunity in animals. Despite all of this intriguing evidence, melatonins mechanism of action on the immune system is only partially defined. It does, however, appear to act through lymphocyte receptors, and perhaps, receptors on other immune tissues, to modulate immune cells. In order to understand immunomodulation and anti-cancer effects, information on melatonin and its interactions with other endocrine hormones are summarized.

Dehydroepiandrosterone (DHEA) sulfate prevents reduction in tissue vitamin E and increased lipid peroxidation due to murine retrovirus infection of aged mice

Abstract Dietary effects of dehydroepiandrosterone sulfate (DHEAS) supplementation on tissue antioxidants and lipids were investigated in retrovirus infected mice. DHEA is a powerful antioxidant and immunomodulator whose production declines with age. For this study, twenty-four female, 15-month-old C57BL/6 mice were left uninfected while twenty-four were infected with LP-BM5 murine leukemia virus, causing murine AIDS. The retroviral infection caused immune dysfunction and loss of hepatic and cardiac vitamins E and A, resulting in increased lipid peroxides. Treatment with DHEAS at 0.01 or 0.005% in drinking water for 10 weeks post-infection significantly (P < 0.05) lowered lipid peroxidation in both heart and liver tissues. Treatment with DHEAS also largely prevented loss of the antioxidants, such as vitamin E and A, and prevented loss of phospholipid in the hearts and livers of the old uninfected as well as infected mice. This study suggests that DHEAS supplementation reduces damage associated with elevated oxidation due to aging and retrovirus infection.

Ethnic variation of the P53 codon 72 polymorphism, HPV persistence, and cervical cancer risk

Association between the p53 codon 72 polymorphism and cervical cancer remains unresolved. We determined the association between the polymorphism and risk of human papillomavirus (HPV) persistence. The polymorphism was detected by restriction enzyme digestion following p53 amplification and HPV detection by the PGMY 09/11 primer set followed by reverse line blot hybridization: 3371 samples were analysed. HPV persistence was assessed on a subset of samples collected at baseline, four and 10 months (n =442). Highly significant differences were observed between ethnic groups (P <0.005). No associations were found between P53 arginine and cytological grade in women infected with any HPV or any oncogenic HPV, despite adjustment for ethnicity. These results were sustained even when HPV-negative women were used as controls. Persistence for any or oncogenic HPV infection was not associated with the polymorphism, irrespective or ethnicity adjustment. Our findings do not support a role for this polymorphism conferring elevated risk for HPV-related disease.

Injection of T‐cell receptor peptide reduces immunosenescence in aged C57BL/6 mice

Previous studies established that retrovirally infected young mice produced large amounts of autoantibodies to certain T‐cell receptor (TCR) peptides whose administration diminished retrovirus‐induced immune abnormalities. C57BL/6 young (4 weeks) and old (16 months) female mice were injected with these same synthetic human TCR Vβ8.1 or 5.2 peptides. Administration of these autoantigenic peptides to old mice prevent immunosenesence, such as age‐related reduction in splenocyte proliferation and interleukin‐2 (IL‐2) secretion. TCR Vβ peptide injection into young mice had no effect on T‐ or B‐cell mitogenesis and IL‐4 production while modifying tumour necrosis factor‐α (TNF‐α), IL‐6, and interferon‐γ (IFN‐γ) secreted by mitogen‐stimulated spleen cells. TCR Vβ injection also retarded the excessive production of IL‐4, IL‐6 and TNF‐α induced by ageing. These data suggest that immune dysfunction and abnormal cytokine production, induced by the ageing process, were largely prevented by injection of selected TCR Vβ CDR1 peptides.

Immune Function in Elderly Smokers and Nonsmokers Improves During Supplementation with Fruit and Vegetable Extracts

Abstract Background: Epidemiological evidence suggests fruits and vegetables reduce the risk of cardiovascular disease (CVD) and cancer. Immune function declines with age as CVD and cancer incidence rises and may be related to poor antioxidant status. Objective: To investigate how fruit and vegetable extracts (Juice Plus™) containing multiple antioxidants and phytonutrients affect immune function in the elderly. Design: Subjects (n = 53; aged 60–86 years, mean = 68 years) consumed extracts for 80 days and two blood samples were taken at baseline and then one at days 40 and 80. Results: Significant increases were found in the serum antioxidants when baseline values were compared with day 80; lutein/zeaxanthin (p