Jayasri Basu

Preeclampsia and antioxidant nutrients: Decreased plasma levels of reduced ascorbic acid, α-tocopherol, and beta-carotene in women with preeclampsia

OBJECTIVE Our purpose was to investigate the plasma levels of three potent antioxidant nutrients in women with preeclampsia. STUDY DESIGN Fasting venous blood samples were collected from 30 women with preeclampsia and from 44 women with uncomplicated pregnancies. The criteria for recruitment included age 15 to 35 years, gestational age 28 to 42 weeks, singleton pregnancy, intact membranes, absence of labor contractions, and absence of any other medical complication concurrent with preeclampsia. Reduced ascorbic acid, alpha-tocopherol, and beta-carotene levels were assayed with high-pressure liquid chromatography. RESULTS Plasma levels of reduced ascorbic acid were significantly decreased in patients with mild and severe preeclampsia (p < 0.01). Plasma alpha-tocopherol and beta-carotene levels were significantly decreased only in severe preeclampsia compared with controls (p < 0.05 and p < 0.05, respectively). CONCLUSION In patients with preeclampsia antioxidant nutrients may be utilized to a greater extent to counteract free radical-mediated cell disturbances, resulting in a reduction in antioxidant plasma levels. Water-soluble antioxidant nutrients may initially be consumed, followed by lipid-soluble antioxidants.

HPV 16 and cigarette smoking as risk factors for high‐grade cervical intra‐epithelial neoplasia

Although genital human papillomavirus (HPV) infection is well established as the etiologic agent for cervical intra‐epithelial neoplasia (CIN), little is known about the cofactors involved in the development of high‐grade lesions or the progression of low‐grade to high‐grade lesions. In our study of HPV‐infected women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with CIN II or III were compared with those with CIN I for risk factors associated with high‐grade lesions. After controlling for age, education, ethnicity and frequency of Pap smear screening, infection with HPV 16, but not high viral load or infection with multiple types, was associated with high‐grade lesions (OR for CIN II = 11.96, OR for CIN III = 23.74). Risk of CIN III, but not CIN II, increased with number of cigarettes smoked per day (ORs = 1.49 and 3.35 for ≤10 and >10 cigarettes per day, respectively) and decreased with frequency of condom use during sex (ORs = 0.60 and 0.32 for women who used condoms occasionally/sometimes and most/all of the time, respectively). There were no associations between high‐grade lesions and plasma levels of micronutrients (retinol, β‐carotene, α‐tocopherol and reduced ascorbic acid). Our results indicate that infection with HPV 16 is associated with high‐grade lesions. Additional cofactors, such as cigarette smoking, may be required as a carcinogen to advance HPV‐infected cells toward neoplastic progression. Int. J. Cancer 78:281–285, 1998.© 1998 Wiley‐Liss, Inc.

Plasma levels of antioxidant β‐carotene and α‐tocopherol in uterine cervix dysplasias and cancer

Abstract Chronic human health problems, namely arteriosclerosis, myocardial ischemia, and cancer, may be caused by highly active oxygen species and may be preventable by antioxidant vitamins. In humans, the sources of two major antioxidants, β‐carotene and α‐tocopherol, are dietary. In this study, we measured the plasma concentrations of s‐carotene and a‐tocopherol by reverse‐phase high‐pressure liquid chromatography in a cross‐sectional sampling of 116 women. Significantly reduced plasma levels of β‐carotene and α‐tocopherol were observed in women with histopathologically diagnosed cervical dysplasias or cancer (p < 0.0001 and p < 0.005, respectively). There was an inverse association between the plasma levels of both β‐carotene and α‐tocopherol and increasingly severe graded cervical histopathology. In groups with advanced dysplasias, the percentage of smokers was markedly increased and the women were comparatively older (p < 0.0001). A strong association was noted between smoking status and plasma β‐ca...

VIRAL CHARACTERISTICS OF HUMAN PAPILLOMAVIRUS INFECTION AND ANTIOXIDANT LEVELS AS RISK FACTORS FOR CERVICAL DYSPLASIA

Genital human papillomavirus (HPV) infection is the major causal factor of cervical intraepithelial neoplasia (CIN). The potential role of nutrition as an additional, independent risk factor for CIN has not been appropriately addressed in the context of HPV. This case‐control study evaluated the etiologic role of HPV in terms of viral type and load and examined the association between CIN and plasma levels of micronutrients adjusting for HPV. Cases (n = 378) with histo‐pathologically confirmed CIN and controls (n = 366) with no history of abnormal Pap smears were recruited from colposcopy and gynecology clinics, respectively. Risk of CIN was significantly increased among women who were infected with multiple HPV types (odds ratio [OR] = 21.06), a high viral load (OR = 13.08) and HPV 16 (OR = 62.49). After adjusting for HPV positivity and demographic factors, there was an inverse correlation between plasma α‐tocopherol and risk of CIN (OR = 0.15). Plasma ascorbic acid was protective at a high level of ≥ 0.803 mg/ dl (OR = 0.46). CIN was not associated with plasma retinol and β‐carotene levels. The effect of genital HPV infection on CIN development is highly influenced by oncogenic viral type and high viral load. Vitamins C and E may play an independent protective role in development of CIN that needs to be confirmed in prospective studies. Int. J. Cancer 78:594–599, 1998.

Plasma vitamin C and uterine cervical dysplasia

Plasma concentrations of vitamin C were determined in a case-control study of women (n = 80) who had sought a Papanicolaou test in the Bronx Municipal Hospital Center. Controls (n = 34) were women having negative cytologic tests, negative colposcopic findings, and no known gynecologic dysfunction. Cases (n = 46) were defined as women who had either one positive or two consecutive suspicious Papanicolaou smears in a 12-month period. The mean concentration of vitamin C in the plasma was significantly lower in the cases than in the controls (0.36 versus 0.75 mg/dl, p less than 0.0001). Cases were further stratified according to the histopathologic diagnosis. The data direct attention to a possible etiologic association of vitamin C in human cervical epithelial abnormalities. A clinical trial with vitamin C intervention is suggested.

Plasma concentrations of micronutrients during α nine‐month clinical trial of β‐carotene in women with precursor cervical cancer lesions

The effects of oral supplementation of a 30-mg dose of beta-carotene on the plasma levels of carotenoids, tocopherols, and retinol were studied sequentially in 69 patients participating in a nine-month randomized placebo controlled trial conducted to examine efficacy of beta-carotene to induce regression of cervical intraepithelial neoplasia. At each visit (baseline and 1.5, 3, 6, 9, 10.5, and 15 mo), blood samples were collected and the levels of six micronutrients were determined by high-performance liquid chromatography. No limitations or changes were introduced in each participants dietary habits. Cervico-vaginal lavage samples were also obtained at the same visit and assayed for the presence of human papillomavirus DNA by Southern blot hybridization and polymerase chain reaction. In the supplemented group, mean plasma beta-carotene levels were significantly higher (p = 0.0001) than baseline and remained markedly elevated for 15 months. In the longitudinal analysis of the placebo group, there were no variations among individual mean plasma levels of beta-carotene, alpha-carotene, lycopene, retinol, gamma-tocopherol, or alpha-tocopherol, suggesting absence of seasonal or dietary changes. In the placebo group, cigarette smoking and steroid contraceptive use were significantly associated with low levels of plasma beta-carotene (p = 0.05 and p = 0.012, respectively). However, in contrast, in the beta-carotene-supplemented group, steroid contraceptive use had no influence on the plasma beta-carotene levels. An additional noteworthy finding was that beta-carotene supplementation did not reverse the depletion effect in smokers. There was no association between the plasma levels of these six micronutrients in women with cervical intraepithelial neoplasia and persistent human papillomavirus infection status in the placebo or the supplemented groups. Functional sequential nutrient interactions with each other or with other essential micronutrients and possible long-term toxicity need to be addressed in clinical trials.

Effects of smoking and oral contraception on plasma β-carotene levels in healthy women

Oral contraceptive use and smoking have been known to affect plasma vitamin levels. Total carotenoids have been studied with spectrophotometry, a relatively insensitive technique. In this study plasma concentrations of beta-carotene and retinol were measured in coded samples by sensitive high-pressure liquid chromatography in a cross-sectional study of 149 normal healthy women attending a family planning clinic. At the time of recruitment in the morning, a general health questionnaire was administered for patient age, methods of contraception, smoking habits, and food intake at breakfast. Of the 149 enrolled volunteers, 88 were oral contraceptive users and 61 were not users. Among users, 21 smoked cigarettes, and there were 18 smokers among nonusers. Oral contraceptive users had significantly lower plasma concentrations of beta-carotene (p less than 0.001) and higher retinol levels (p less than 0.0001). Plasma beta-carotene or retinol levels did not differ among users of intrauterine contraceptive devices or barrier methods of contraception. No association was noted between the plasma levels of these two micronutrients and age greater than or less than 30 years. Cigarette smoking alone was associated with significantly reduced plasma beta-carotene levels in nonusers (p less than 0.001). Combined cigarette smoking and oral contraceptive usage were associated with low plasma beta-carotene levels; the results appear to be additive. These findings suggest a possible synergistic effect on plasma beta-carotene levels from the use of both cigarette smoking and oral contraception.

Chemoprevention of cervix cancer: Phase I–II: A feasibility study involving the topical vaginal administration of retinyl acetate gel

A Phase I-II clinical trial has been conducted with a retinyl acetate (RA) gel applied cervicovaginally in women having a histopathologic lesion diagnosed as mild or moderate dysplasia. With informed consent, volunteer subjects were observed and followed with Pap smears and colposcopy in a standardized protocol involving a self-administered 7-day treatment course for three successive menstrual cycles. Varying dosages of RA including placebo, 3, 6, 9, and 18 mg per 6 g of an inert vehicle were employed. A total of 50 subjects were monitored for local and systemic side effects. No intolerable side effects or disturbing toxicity was reported or detected at any of these doses. With the 18-mg dosage, significant discomfort was reported by all women. Despite associated side effects and a considerable patient effort involved in carrying out the self-administration of the gel, a high level of compliance was achieved in this trial. It has been established that women will voluntarily participate in an intervention clinical trial to determine whether retinyl acetate is an alternative method of therapy of presumed precancerous lesions of the cervix. The analysis of the side effects of the gel at the various dosage concentrations favors the selection of the 9-mg dosage for a multicenter Phase III clinical trial to determine efficacy.

Smoking and the antioxidant ascorbic acid: Plasma, leukocyte, and cervicovaginal cell concentrations in normal healthy women

The influence of cigarette smoking on the plasma, leukocyte, and cervicovaginal cell ascorbic acid levels in 46 healthy smokers and healthy nonsmokers was investigated. Coded peripheral venous blood and cervicovaginal lavage specimens obtained after informed consent were analyzed simultaneously for their ascorbic acid content. The findings suggest that smoking affects the levels and distribution of ascorbic acid. In smokers (n = 16), the number of exfoliated cervicovaginal epithelial cells and leukocyte ascorbic acid levels was significantly higher (p less than 0.01, p less than 0.05, respectively) compared with nonsmokers (n = 30). In addition, cervicovaginal cell ascorbic acid, plasma reduced and total ascorbic acid levels were significantly lower (p less than 0.001, p less than 0.01, p less than 0.01, respectively). The exfoliated epithelial cell ascorbic acid levels in nonsmokers was fourfold greater than that of leukocytes. The implications of these findings within the context of free radical-induced cellular pertubations in smokers are discussed.

β-carotene levels in exfoliated cervicovaginal epithelial cells in cervical intraepithelial neoplasia and cervical cancer

Abstract OBJECTIVE: The purpose of this study was to measure β-carotene levels in exfoliated epithelial cervicovaginal cells collected by a lavage technique in normal women and patients with histopathologically diagnosed cervical intraepithelial neoplasia and cervical cancer. STUDY DESIGN: In a cross-sectional sampling of women ( n = 105), cervicovaginal cells and plasma β-carotene levels were assayed with high-pressure liquid chromatography. In addition, β-carotene levels were measured in exfoliated epithelial samples of cervicovaginal cells obtained from women ( n = 24) enrolled in an ongoing oral β-carotene supplementation clinical trial. RESULTS: Cervicovaginal cells and plasma β-carotene levels were found to be significantly decreased in women with cervical intraepithelial neoplasia and cervical cancer as compared with controls ( p \lt 0.0001, analysis of variance). Retinol levels in cervicovaginal cells were undetectable. The β-carotene levels in cervicovaginal cells were markedly increased in the majority of patients (79%) after oral supplementation as compared with baseline levels in women enrolled in the β-carotene clinical trial. CONCLUSION: The study demonstrates that changes of in situ cellular β-carotene concentrations are measurable in samples of exfoliated epithelial cells obtained by a noninvasive saline lavage harvesting technique. The current findings further support our previous hypothesis that β-carotene deficiency may have an etiologic role in the pathogenesis of cervical intraepithelial neoplasia and/or cervical cancer. (AM J OBSTET GYNECOL 1992;167:1899-903.)