Plasma concentrations of coenzyme Q10 and tocopherols in cervical intraepithelial neoplasia and cervical cancer.

Cervical intraepithelial neoplasia (CIN) may, at times, unpredictably progress to invasive carcinoma of the cervix. Epidemiological nutritional studies suggest that higher dietary consumption and circulating levels of certain micronutrients may be protective against cervical cancer. However, a preventive role of dietary antioxidants in CIN is not well established. The purpose of this cross-sectional study was to investigate the comparative plasma concentrations of three potent antioxidants, coenzyme Q(10,) alpha-tocopherol and gamma-tocopherol, in women with normal Pap smears and patients with a biopsy-confirmed histopathological lesion diagnosed as CIN or cervical cancer. Plasma concentrations of coenzyme Q(10,) alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography in both normal women without any history of abnormal Pap smears (n=48), and patients with histopathologically confirmed diagnoses of: (a) CIN I, n=98; (b) CIN II, n=49; (c) CIN III, n=10; and (d) cervical cancer, n=25. The mean plasma levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were significantly lower (P<0.001,<0.001, and<0.001, respectively by Kruskal-Wallis test) in patients with various grades of CIN and cervical cancer compared with controls. After controlling for age and smoking, an inverse association between histological grades of epithelial lesions and both plasma coenzyme Q(10) and alpha-tocopherol concentrations was observed. The low plasma concentrations of coenzyme Q(10) may be due to deficient dietary intake or a decrease in endogenous coenzyme Q(10) biosynthesis that may reflect increased utilization as a result of free radical reactive oxygen species induced oxidative stress. Further molecular studies on the mechanistic role of antioxidants in women with precancer cervical lesions are needed.

Placental and serum levels of carotenoids in preeclampsia.

OBJECTIVE: We compared placental tissue, maternal serum, and umbilical cord venous blood levels of four dietary carotenoids (alpha-carotene, beta-carotene, lycopene, and canthaxanthin) in normal pregnant women and those with preeclampsia. METHODS: Levels of alpha-carotene, beta-carotene, lycopene, and canthaxanthin were measured in placental tissue, maternal serum, and umbilical cord venous blood from 22 normal pregnant women and 19 women with preeclampsia. The criteria for recruitment included gestational age of 30-42 weeks, singleton pregnancy, intact membranes, absence of labor contractions, and absence of any other medical complication concurrent with preeclampsia. Carotenoids were measured using high-pressure liquid chromatography. RESULTS: All four carotenoids were detectable in human placental tissue, maternal serum, and umbilical cord venous blood samples. The levels of beta-carotene, lycopene, and canthaxanthin in placentas from preeclamptic women were significantly lower (P =.032, .009, and .013, respectively, by Mann-Whitney test) than those from normal pregnant women. Maternal serum levels of beta-carotene and lycopene were significantly lower (P =.004 and .008, respectively, by Mann-Whitney test) in women with preeclampsia. However, umbilical cord venous blood levels of these carotenoids were not significantly different between the two groups. CONCLUSION: Lower placental tissue and maternal serum carotenoid levels in women with preeclampsia suggest that oxidative stress or a dietary antioxidant influence might have an effect on the pathophysiology of preeclampsia.

Apoptotic changes in cervical intraepithelial neoplasia.

We examined apoptosis in paraffin-embedded archival cervical tissues from cervical intraepithelial neoplasia (CIN) cases to determine whether the apoptotic process is involved in the cellular changes of CIN. Apoptotic bodies, determined by the Tunel method, were largely found at the surface epithelium in a few tissue specimens with no significant abnormality and in most tissues with CIN. Apoptotic bodies were also found within the stratified epithelium of CIN lesions and were altogether absent in specimens with no significant abnormalities. The apoptotic index was significantly associated with the severity of CIN and not with either age or human papillomavirus infection. Based on the findings of increased numbers of apoptotic bodies and their presence within the stratified epithelium in CIN tissues, we hypothesize that dysregulation in the exfoliation of apoptotic cells and resistance towards apoptosis may be prerequisites for the pathogenesis of CIN.

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 alpha-tocopherol and risk of CIN (OR = 0.15). Plasma ascorbic acid was protective at a high level of > or = 0.803 mg/dl (OR = 0.46). CIN was not associated with plasma retinol and beta-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.

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 intraepithelial 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 < or = 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, beta-carotene, alpha-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.

Plasma concentrations of micronutrients during a nine-month clinical trial of beta-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 participant's 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.

Stringent criteria for histological diagnosis of koilocytosis fail to eliminate overdiagnosis of human papillomavirus infection and cervical intraepithelial neoplasia grade 1.

Overdiagnosis of HPV infection in cervical biopsies results in increased health care costs and unnecessary surgical procedures. Stringent criteria for histological diagnosis of koilocytosis were evaluated, using molecular detection of HPV DNA (polymerase chain reaction and Southern blot hybridization) as gold standard. Colposcopic biopsy specimens from 511 patients were studied, including 76 with referral diagnoses of negative cervix and 241 with CIN 1 or koilocytosis. Referral diagnoses for low-grade lesions failed to distinguish between HPV-infected and uninfected patients. False-positive rate for prediction of HPV infection was 74.8%. Biopsy specimens reevaluated using stringent diagnostic criteria showed increasing prevalence of HPV infection among patients whose biopsy specimens showed negative (43.7%), minimal (52.4%), or definite (69.5%) features of koilocytosis (P = .001). Similarly, subjects infected with high viral load or oncogenic HPV infection were more likely to be identified (P = .004 and .04, respectively). Despite increased predictive value of stringent diagnostic criteria, significant number of patients diagnosed as having CIN 1/koilocytosis (34.0%) did not in fact have HPV infection. Because most low-grade lesions spontaneously regress, patients with histological diagnosis of CIN 1 or HPV infection should be observed for a period of several months before definitive ablative treatment is undertaken.

Lymphoproliferative responses to human papillomavirus (HPV) type 16 proteins E6 and E7: outcome of HPV infection and associated neoplasia.

BACKGROUND: Infection with human papillomavirus (HPV) type 16 (HPV16) is a major cause of high-grade cervical intraepithelial neoplasia (CIN). Experiments were planned to evaluate the role of cell-mediated immunity (e.g., lymphocyte proliferation) against HPV in the natural history of HPV-associated neoplasia and to identify antigenic sequences of the HPV16 proteins E6 and E7 against which an immune response may confer protection. METHODS: Forty-nine women with abnormal cervical cytology and biopsy-confirmed CIN were followed through one or more clinic visits. Lymphoproliferative responses of peripheral blood mononuclear cells to HPV16 E6 and E7 peptides were assessed in long-term (3-week) cultures. HPV DNA was detected in cervicovaginal lavage by means of polymerase chain reaction and Southern blotting. Disease status was determined by cervical cytologic examination and colposcopy. Reported P values are two-sided. RESULTS: Subjects with positive lymphoproliferative responses to E6 and/or E7 peptides were more likely to be HPV negative at the same clinic visit than were nonresponders (P = .039). Subjects who were negative for HPV and those with a low viral load were more likely to be responders than were those with a high viral load (P for trend = .037). Responses to N-terminal E6 peptide 369 were associated with absence of HPV infection at the same clinic visit (P = .015). Subjects with positive responses to E6 or E7 peptides at one clinic visit were 4.4 times more likely to be HPV negative at the next visit than were nonresponders (P = .142). Responses to E6 peptide 369 and/or E7 C-terminal peptide 109 were associated with an absence of HPV infection (P = .02 for both) and an absence of CIN (P = .04 and .02, respectively) at the next visit. CONCLUSIONS: Lymphoproliferative responses to specific HPV16 E6 and E7 peptides appear to be associated with the clearance of HPV infection and the regression of CIN.

Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection.

Women with histopathologically confirmed cervical intraepithelial neoplasia (CIN) were followed at 3-month intervals in a randomized double-blinded trial to evaluate the efficacy of beta-carotene to cause regression of CIN. Questionnaire data, plasma levels of micronutrients, and a cervicovaginal lavage for human papillomavirus (HPV) detection were obtained at each visit, and an endpoint biopsy was performed at 9 months. Sixty-nine subjects had a biopsy endpoint evaluation; 9 of 39 (23%) subjects in the beta-carotene group versus 14 of 30 (47%) in the placebo group had regression of CIN (P = 0.039). Independent risk factors for persistent CIN at 9 months included type-specific persistent HPV infection (OR = 11.38, P = 0.006) and continual HPV infection with a high viral load (OR = 14.25, P = 0.007) at baseline and 9 months, an initial diagnosis of > or =CIN II (OR = 6.74, P = 0.016), and older age (OR for > or =25 years = 4.10, P = 0.072). After controlling for these factors, the beta-carotene and placebo groups did not differ in risk for having CIN at 9 months (OR = 1.53, P = 0.550). Resolution of baseline HPV infection was significantly correlated with non-high-risk HPV types (RR = 2.94, P = 0.015), age <25 years (RR = 2.62, P = 0.014), and douching after sexual intercourse (RR = 3.02, P = 0.012), but not with randomization group. Our data indicate that a large proportion of mild CIN lesions regress; age and HPV infection play an important role in the natural course of CIN; and repeated HPV testing may have a value in distinguishing women who need aggressive treatment for CIN versus those who do not. Supplementation of beta-carotene does not appear to have a detectable benefit in treatment of CIN.

Induction of transforming growth factor beta-1 in cervical intraepithelial neoplasia in vivo after treatment with beta-carotene.

Transforming growth factor (TGF) beta1 is a potent growth inhibitor of epithelial cells. Loss of responsiveness to TGF-beta1 and/or loss of TGF-beta1 itself may be important in the progression of cervical intraepithelial neoplasia to invasive cervical cancer. Retinoids have antiproliferative effects on epithelial cells and have been used as chemopreventive and chemotherapeutic agents for several human cancers. There is evidence that retinoids exert their effects by promoting the induction of TGF-beta. The aim of this study was to determine whether the expression of TGF-beta1 was altered in patients enrolled in a clinical trial designed to test the therapeutic efficacy of beta-carotene, a carotenoid metabolized to retinol, in cervical intraepithelial neoplasia. Using an immunohistochemical technique, tissues were stained with two types of antisera that react with the intracellular and extracellular forms of TGF-beta1. Matched cervical biopsies taken from 10 patients before and after treatment with beta-carotene were immunostained simultaneously to allow direct comparison of relative staining intensity. A significant increase in intracellular TGF-beta1 immunoreactivity was noted in cervical epithelial cells in patients with cervical intraepithelial neoplasia after treatment with beta-carotene (P = 0.003). These results demonstrate regulation of a TGF-beta isoform in vivo in humans in response to beta-carotene administered as a chemopreventive agent.

Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer.

Epidemiological studies continue to identify an association of dietary antioxidant micronutrients in cancer prevention. A number of case-control and cohort studies have demonstrated a relationship between high intake of foods rich in carotenoids, tocopherols, and vitamin C with a reduced risk of certain human malignancies. The purpose of this study was to investigate the comparative plasma levels of a profile of known dietary antioxidants, namely, beta-carotene, lycopene, canthaxanthin, retinol, alpha-tocopherol, and tau-tocopherol. The target population was women with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) or cervical cancer and a control group. All women resided in the same catchment area (Bronx Borough, New York City) and were of similar inner-city socioeconomic backgrounds representing a fairly homogenous population group. A cross-sectional sample of 235 women was recruited with informed consent. Plasma nutrient levels were measured by reverse-phase high pressure liquid chromatography under study codes. The mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, were significantly lower in women with CIN and cervical cancer. In contrast, the mean plasma level of tau-tocopherol was higher among patients with CIN, while the mean plasma level of retinol was comparable among the groups. There were significant linear trends for all three carotenoids and quadratic trends for alpha- and tau-tocopherol with the degree of cervical histopathology. Plasma beta-carotene concentrations in cigarette smokers were significantly lower regardless of cervical pathology, whereas plasma lycopene and canthaxanthin levels were significantly lower in smokers with CIN. The findings of a decrease in all plasma antioxidant nutrient levels except tau-tocopherol in women with CIN and cancer suggest a potential role for antioxidant deficiency in the pathogenesis of CIN and carcinoma of the cervix, which requires further investigation.

Computerized colposcopy and conservative management of cervical intraepithelial neoplasia in pregnancy.

BACKGROUND: Computerized colposcopy is the noninvasive digital processing of colposcopic images acquired using a charge-coupled device camera. The purpose of this study was to evaluate the clinical applications of computerized colposcopy, and to record the colposcopic changes associated with progression or regression of cervical intraepithelial neoplasia in pregnancy. METHODS: Forty-one pregnant patients, with abnormal Papanicolaou smears and a fully visualized squamo-columnar junction, were serially monitored throughout their pregnancies using computerized colposcopy. All patients had baseline computer-assisted measurements of their cervical lesions and a repeat measurement at monthly intervals and at 3-months postpartum. RESULTS: During the period of gestation, 17.1% of lesions increased in size, 21.9% remained unchanged, 41.5% decreased in size and 19.5% disappeared completely. In patients with an increase in lesion size, a colposcopically directed punch biopsy was performed which revealed CIN III but no microinvasion. Cervical biopsy during pregnancy was unnecessary in 82.9% of cases. CONCLUSION: The ability to sequentially monitor and quantify colposcopically visualized lesions, using computerized colposcopy, provides a noninvasive objective mode to evaluate progression, stability, or regression of CIN lesions during pregnancy.

Effects of smoking on the levels of antioxidant beta carotene, alpha tocopherol and retinol in human ovarian follicular fluid.

The concentrations of beta-carotene, retinol and alpha-tocopherol were measured by high-pressure liquid chromatography in ovarian follicular fluid and plasma samples collected at the time of oocyte recovery from patients enrolled in our in vitro fertilization program. The mean beta-carotene levels in follicular fluid [0.182 +/- (SEM) 0.04 nmol/ml] and plasma (0.37 +/- 0.34 mmol/ml) of smokers (n = 5) were significantly (p < 0.025 and p < 0.001, respectively) lower compared with the mean levels in follicular fluid (0.58 +/- 0.10 nmol/ml) and plasma (1.11 +/- 0.09 mmol/ml) in nonsmokers (n = 11). The follicular fluid and plasma retinol and alpha-tocopherol levels were comparable among the nonsmokers and smokers. These findings direct attention to a possible role of the antioxidant beta-carotene, per se, as a biological marker in ovarian oocyte follicular maturation and function.

Lipid profile in women with preeclampsia: relationship between plasma triglyceride levels and severity of preeclampsia.

It has been hypothesized that, in preeclampsia, hypertriglyceridemia may lead to increased endothelial triglyceride accumulation that, in turn, may result in endothelial cell damage. The purpose of our study was to determine whether hypertriglyceridemia is associated with the severity of preeclampsia. We studied 29 preeclamptic patients and 46 normal pregnant women, aged 15 to 35 years, with singleton pregnancies, at 28 to 37 weeks' gestation. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were measured enzymatically. High-density lipoprotein cholesterol was determined using a dextran sulfate-magnesium precipitation method. Patients with mild preeclampsia had a significant increase in plasma triglyceride levels (P < .001), while patients with severe preeclampsia had triglyceride levels comparable to controls. Our findings suggest that there is no direct relationship between triglyceride levels and severity of preeclampsia.

Nutrient antioxidants in the pathogenesis and prevention of cervical dysplasias and cancer.

The role of nutritional factors in biochemical interactions that are part of an oncogenic process or inhibit free radical proliferation have attracted considerable interest in relation to molecular mechanism(s) and the natural history of human cancer. Epidemiologic and experimental studies have drawn attention to the association between dietary micronutrient deficiencies and the incidence of neoplastic and malignant lesions. In the last two decades, the role(s) of retinoids, carotenoids, tocopherols and water-soluble antioxidant vitamins, and allegations of anti-tumor properties in the daily dietary consumption of fresh fruits and green leafy vegetables, have captured the attention of an increasingly sensitive diet- and health care-conscious public, the biochemical community, and industrial food producers. Moreover, recent epidemiologic and compelling advances in molecular biology have linked the presence of restricted human papillomavirus (HPV) subtypes to cervical carcinoma and precursor lesions. In the present report, we identify and review measurable effects of dietary deficiencies of selected antioxidant micronutrients (i.e., beta-carotene and vitamins A, C, and E) and their association with known cervix cancer risk factors in the pathogenesis and potential prevention of cervix dysplasias, presumed to be the precursor lesions of cervix cancer.

Lipid-soluble antioxidants: beta-carotene and alpha-tocopherol levels in breast and gynecologic cancers.

Free radical-induced damage is etiologically implicated in many chronic diseases including cancer. Epidemiologic data suggest an association between increased dietary intake of nutrients that are high in antioxidant vitamins and protection against the incidence of some human cancers. The purpose of this study was (a) to determine whether specific tissue antioxidants (beta-carotene and alpha-tocopherol) and any differences in their levels were measurable in randomly selected human breast and gynecologic malignant neoplasms and nonneoplastic tissue samples obtained from the same patient and (b) to establish normal ranges of these two antioxidant levels in human female reproductive tract tissues. Tissue samples were excised immediately from surgical specimens and released by staff pathologists from a spectrum of human female cancers. Neoplastic and adjacent nonneoplastic tissues samples were obtained from the same patient. Normal reproductive tract tissue samples were obtained from women undergoing hysterectomy for benign gynecologic conditions. Breast carcinoma and adjacent nonmalignant tissue specimens were obtained from women undergoing mastectomy. The concentrations of beta-carotene and alpha-tocopherol were measured by high-pressure liquid chromatography. In the same patient, beta-carotene levels were significantly lower in the cervical (P < 0.01) and endometrial (P < 0.005) carcinoma tissues than the levels detectable in adjacent nonneoplastic sites. In contrast, beta-carotene levels were higher in the ovarian (P < 0.05), breast (P < 0.005), and vulva (P < 0.05) carcinoma tissues. The alpha-tocopherol concentrations were significantly higher in the cancer tissues of cervix (P < 0.01) and endometrium (P < 0.001) than those in adjacent noninvolved tissue sites. The tissue concentrations of alpha-tocopherol in malignant and adjacent normal sites in breast, ovary, and vulva were comparable. For the first time, the ranges for beta-carotene and alpha-tocopherol levels in the normal female reproductive tract tissues were also established. The present findings of contrasting tissue levels of the antioxidants (beta-carotene and alpha-tocopherol) in breast, cervix, endometrium, ovary, and vulva cancers and in nonneoplastic tissues of the same patient suggest an organ-specific and heterogenous distribution. These antioxidants appear to be essential nutritional requirements of the human female reproductive tract and breast and are implicated in the pathophysiology and carcinogenesis of these human organs. The findings require further study of the role of these antioxidant nutrients in epithelial cell proliferation, maturation, and differentiation.

Decreased beta-carotene levels in exfoliated vaginal epithelial cells in women with vaginal candidiasis.

PROBLEM: Women are more susceptible to vaginal candidiasis when the host immune response is suppressed. The antioxidant nutrient beta-carotene is postulated to possess immunoenhancing properties. The purpose of this study was to investigate beta-carotene concentrations in exfoliated vaginal epithelial (EVE) cells in women with vaginal candidiasis. METHODS: Beta-carotene levels in EVE cells, collected by a saline lavage technique from 22 women with vaginal candidiasis and 20 normal controls, were analyzed. The diagnosis of vaginal candidiasis was established by the presence of pruritus, white cheesy vaginal discharge, and a positive potassium hydroxide preparation. Beta-carotene levels were assayed using high pressure liquid chromatography. RESULTS: Vaginal cell concentrations of beta-carotene were significantly decreased in women with vaginal candidiasis (P < 0.001). CONCLUSIONS: Decreased beta-carotene levels, and possibly other antioxidants, may alter the local immune response resulting in disturbances in the vaginal flora, overgrowth of candida, and the development of vaginal candidiasis.

Cell-mediated immune responses to E7 peptides of human papillomavirus (HPV) type 16 are dependent on the HPV type infecting the cervix whereas serological reactivity is not type-specific.

Forty-two women attending a colposcopy clinic for evaluation of abnormal cervical cytology and 13 normal controls were studied for the presence of lymphocyte proliferation (LP) cell-mediated immune (CMI) responses and serological reactivity to E7 peptides of human papillomavirus type 16 (HPV-16). HPV was typed by Southern blot hybridization of exfoliated cervicovaginal cell DNA. Positive LP responses (stimulation index > or = 5.0) to one or more E7 peptides were observed in 28.6% (12 of 42) of patients and 23.1% (three of 13) of controls. Of patients infected with HPV-16, -31 or -33, 63.6% (seven of 11) showed a positive LP response compared with 14.3% (two of 14) of women infected with other HPV types (P = 0.02), 17.6% (three of 17) negative for HPV (P = 0.02) and 23.1% (three of 13) of controls (HPV status unknown) (P = 0.05). C-terminal peptide 109 (amino acids 72 to 97) elicited positive LP responses in 45.4% (five of 11) of patients infected with HPV -16, -31 or -33 compared with 7.1% (one of 14) patients infected with other HPVs (P = 0.04), 5.9% (one of 17) of women negative for HPV (P = 0.02) and 7.7% (one of 13) of controls (P = 0.05). HPV-16 group-specific LP responses of borderline significance were also observed against E7 peptides 103, 105 and 108 (17-37, 37-54 and 62-80) (P = 0.07). ELISA reactivity (IgG) to E7 peptide 109 (72-97) was present in 7.7% (one of 13) of controls, 35.3% (six of 17) of HPV-negative patients, 42.9% (six of 14) of patients infected with other HPVs, and only 9.1% (one of 11) of patients infected with HPV-16, -31 or -33. CMI responses to C-terminal HPV-16 E7 peptide 109 (72-97) were thus significantly related to ongoing cervical infection with HPV-16 and closely related types, whereas serological reactivity to E7 peptides was not HPV type-specific.

Preeclampsia and antioxidant nutrients: decreased plasma levels of reduced ascorbic acid, alpha-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.