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Biomedical subjects

Manubai Nagamani

Publications and source records attributed to Manubai Nagamani.

12 recordsLinked to original sources
PubMed2006

A strong association between body fat mass and protein profiles in nipple aspirate fluid of healthy premenopausal non-lactating women.

Fluid can be aspirated from the nipples of most non-lactating women. This nipple aspirate fluid (NAF) is a potential source for the discovery of new breast cancer biomarkers. NAF has two distinct protein profiles. Type I NAF is similar to the fluid associated with cystic disease of the breast, whereas type II NAF is enriched in milk-associated proteins. The prevalence of these two profiles differs in healthy women and in breast cancer patients. This study investigated the relationship of these two NAF profiles to reproductive history, body composition, diet, and levels of lipids, steroids and thyroid hormones in healthy premenopausal women (age 30-40 years) who had regular menstrual cycles and normal mammograms and were not taking contraceptive medications. On average, women with the type I NAF profile were older, had more years since last childbirth, were less likely to have breastfed their babies and had higher dietary saturated fat intake, body mass index, body fat mass, and levels of plasma low density lipoproteins than women with the type II profile (P <0.05). Using multiple logistic regression, type I NAF was predicted independently (P <0.05) by higher body fat mass [Odds Ratio (OR) = 3.0; 95% Confidence Interval (CI): 1.5-6.1], more years since last childbirth (OR = 2.6; 95% CI: 1.3-5.2) and a higher percentage of calories from saturated fat (OR = 4.1; 95% CI: 1.1-14.6). These results suggest that protein profiles of NAF might be influenced by amounts or types of dietary and body fat, but further study of the relationship of the two profiles to breast cancer risk is needed.

Adipose Tissue↗
PubMed2006

Serum soluble leptin receptor levels and free leptin index in women with polycystic ovary syndrome: relationship to insulin resistance and androgens.

OBJECTIVE: To evaluate levels of soluble receptor (sOB-R) and free leptin in women with polycystic ovarian syndrome (PCOS) and note any relationships with insulin resistance, adiposity, and androgens. Leptin is an adipokine that circulates in a free form and bound to an sOB-R. Only free leptin is biologically active. DESIGN: Prospective, case-control study. SETTING: University-based reproductive endocrinology practice. PATIENT(S): Forty women with PCOS and severe insulin resistance and 15 body mass index (BMI)-matched ovulatory controls. INTERVENTION(S): Measurements of serum insulin, leptin, sOB-R at fasting and during a standard oral glucose tolerance test (OGTT), and measurements before and after treatment with rosiglitazone. MAIN OUTCOME MEASURE(S): Fasting glucose, insulin, leptin, sOB-R, T, and DHEAS levels in women with PCOS and controls were measured to investigate the relationship of sOB-R and the free leptin index (FLI) to insulin, adipocity, and androgens and to investigate the effect of acute hyperinsulinemia during OGTT and the effect of improvement of insulin resistance with rosiglitazone on the leptin system. FLI was calculated by dividing leptin levels by sOB-R. RESULT(S): Total leptin and FLI correlated significantly with BMI in both patients with PCOS and in controls. There was a significant negative correlation between DHEAS and sOB-R in PCOS. Leptin, sOB-R, and FLI were not significantly different in the two groups, and neither sOB-R nor FLI correlated with insulin or glucose levels. The sOB-R levels increased significantly 3 hours after oral glucose ingestion, resulting in a significant decline in FLI. CONCLUSION(S): [1] Adiposity rather than insulin resistance appears to be the main determinant of leptin levels and FLI. [2] Acute increase in insulin levels during OGTT is associated with an increase in levels of sOB-R. [3] DHEAS may play a role in leptin bioavailability by modulating sOB-R levels.

Acanthosis Nigricans↗
PubMed2006

Ovarian dysfunction in peripubertal hyperinsulinemia.

OBJECTIVE: Increasing evidence suggests that hyperinsulinemia plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the timing for the onset of hyperinsulinemia is not clear. The objective of this study was to examine the effect of peripubertal hyperinsulinemia on the maturing female reproductive axis. METHODS: Hyperinsulinemia was induced in 28-day-old peripubertal female rats by infusing insulin (0.04 IU/d) via subcutaneously implanted Alzet minipumps (Model #2004; Durect Corp, Cupertino, CA; constant flow rate 0.25 muL/h) for 4 weeks. Control animals were administered normal saline. Estrus cyclicity was monitored regularly. Upon termination of the experimental period, the animals were killed, trunk blood and pituitaries were collected for hormone assays, and ovaries were collected for histological and immunocytochemical studies. RESULTS: In contrast to the control animals, hyperinsulinemic animals had (1) erratic estrus cycles, with prolonged (2 to 3 days) metestrus-diestrus or diestrus-proestrus stages; (2) significantly (P <.05) decreased levels of serum progesterone, and significantly (P <.05) increased levels of serum testosterone and dehydroepiandrostene sulfate; (3) prematurely luteinized ovarian follicles with prominent thecal and interfollicular stromal proliferation; and (4) markedly reduced expression of growth differentiation factor-9 (GDF-9) and activin receptors (ActR) I and IB in the ovaries. CONCLUSION: Peripubertal hyperinsulinemia in rats causes hormonal and ovarian changes similar to those in women with PCOS. Based on these novel findings, we speculate that peripubertal hyperinsulinemia may be a risk factor for the development of PCOS later in life.

Activin Receptors, Type I↗
PubMed2005

Decreased circulating levels of tumor necrosis factor-alpha in postmenopausal women during consumption of soy-containing isoflavones.

CONTEXT: TNF-alpha is a key mediator of inflammatory responses and may play a pivotal role in the development of cancer and in bone resorption. OBJECTIVE: This study determined the effect of soy rich in isoflavones on levels of TNF-alpha. DESIGN: Twelve postmenopausal women ingested a 36-oz portion of soymilk containing isoflavones daily for 16 wk and provided fasting blood samples multiple times before, during, and after soy consumption for the analyses of cytokines and monocyte content. RESULTS: Compared with prediet levels (36.3 +/- 14.0 pg/ml), serum levels of TNF-alpha decreased by 25.1% (27.2 +/- 10.3 pg/ml; P < 0.01) as early as 2 wk after soy consumption and by 66.7% (11.6 +/- 5.3 pg/ml; P < 0.01) 10 wk after soy consumption and recovered to the prediet levels 4 wk after the termination of soy consumption (38.6 +/- 19.6 pg/ml; P = 0.66). A similar decrease of up to 56.6 and 14.4% was found for serum IL-1alpha and the mean percentage of blood monocytes during soy consumption, respectively, but not for IL-6. In cultures of monocytes or whole blood from postmenopausal women, soy isoflavones (genistein and daidzein, 10-1000 nm), tamoxifen (10-1000 nm), or 17beta-estradiol (0.1-10 nm) inhibited lipopolysaccharide (1 microg/ml)-induced TNF-alpha production by up to 55.8%. CONCLUSIONS: Isoflavones may be the active components in soy responsible for the decrease of TNF-alpha found in postmenopausal women during a soy diet. This antiinflammatory effect of the isoflavones may be important in immune modulation and the prevention of bone loss and cancer.

Aged↗
PubMed2005

Adverse effects of methylphenidate on the reproductive axis of adolescent female rats.

OBJECTIVE: To examine the effects of chronic methylphenidate use on the reproductive axis of adolescent female rats. DESIGN: Controlled prospective study. SETTING: University research laboratory. ANIMAL(S): Twenty prepubertal female Sprague Dawley rats. INTERVENTION(S): Subcutaneous implantation of drug-filled Alzet minipumps (Durect Corporation, Cupertino, CA) for infusing methylphenidate (450 microg/d, treated) or physiological saline (control) for 4 weeks. Estrous cyclicity was checked from 3 weeks of pump implantation till the termination of the experiments. Animals were killed after 4 weeks of treatment. MAIN OUTCOME MEASURE(S): Estrous cyclicity, pituitary and peripheral FSH and LH, serum estrogen and progesterone, ovarian histology, and immunocytochemistry for localizing growth differentiation factor-9 and activin receptors-I. RESULT(S): Compared with the control group, the treated animals exhibited the following: [1] poor vaginal opening and erratic estrous cyclicity; [2] undeveloped, disrupted, or prematurely luteinized ovarian follicles; [3] absence of growth differentiation factor-9 and of activin receptors I and IB in the oocyte; and [4] high levels of LH in the pituitary. CONCLUSION(S): Chronic methylphenidate administration during adolescence perturbs pubertal onset, adversely affects maturation of the female reproductive axis by retarding pituitary LH release, and adversely affects ovarian folliculogenesis. These novel findings may have significant clinical implications in evaluating the effects of methylphenidate abuse on adolescent health.

Age Factors↗
PubMed2005

Adiponectin levels in women with polycystic ovary syndrome and severe insulin resistance.

OBJECTIVE: Adiponectin is an adipokine that is decreased in obesity and type 2 diabetes. Women with polycystic ovarian syndrome (PCOS) are obese and are at risk for type 2 diabetes. The objective of the current study was to investigate the relationship of adiponectin to obesity and insulin resistance in women with PCOS and severe insulin resistance. METHODS: Thirty women with PCOS and acanthosis nigricans indicating severe insulin resistance were included in the study. Eleven body mass index (BMI)-matched women with normal ovulatory cycles served as controls. Fasting glucose, insulin, and adiponectin levels were measured, and a standard oral glucose tolerance test (OGTT) with insulin levels was performed. To further investigate the role of insulin sensitivity on adiponectin levels, 10 women with PCOS were treated with 4 mg rosiglitazone daily for 6 months and adiponectin levels were measured before and after treatment. RESULTS: Fasting insulin levels (33.5 +/- 3.8 microU/mL; P <.001) and insulin area under the curve (AUC) during OGTT (536.2 +/- 70.5 microU/mL; P <.01) were higher in women with PCOS, while glucose levels were similar to controls. Adiponectin levels were lower (P <.01) in women with PCOS (5.6 +/- 2.6 microg/mL) compared with controls (8.5 +/- 3.9 microg/mL). There was a significant negative correlation between adiponectin levels and fasting insulin levels (r = -0.40, P = .02), insulin AUC during OGTT (r = -0.47, P = .008), fasting glucose levels (r = -0.45, P = .01), and glucose AUC during OGTT (r = -0.51, P = .003). There was no correlation between BMI and serum adiponectin (r = -0.12, P = .508) in women with PCOS, while there was a negative correlation (r = -0.746, P = .013) in controls. There was a significant (P <.01) increase in adiponectin levels when treated with rosiglitazone, despite unchanged BMI. CONCLUSION: These results indicate that in women with PCOS and severe insulin resistance, insulin sensitivity appears to be the major determinant of adiponectin levels rather than adiposity. Low adiponectin levels may predict women with PCOS who are at high risk for developing type 2 diabetes.

Adiponectin↗
PubMed2005

Effect of a soymilk supplement containing isoflavones on urinary F2 isoprostane levels in premenopausal women.

Epidemiological studies have associated soy diets with reduced risk of breast and some other cancers, and oxidative cellular damage may contribute to the development of these and other diseases. We tested the effect of a soymilk supplement rich in isoflavones on a measure of cellular lipid peroxidation in a controlled feeding study. Eight premenopausal women consumed a constant diet that included soymilk containing 113-207 mg/day total isoflavones and 4 mo later a constant soy diet low (<5 mg/day) in isoflavones, both for a complete menstrual cycle. The average daily urinary excretions of daidzein and genistein were 24.6 +/- 10.1 and 9.2 +/- 6.1 mg/day, respectively, during the high-isoflavone soy diet and were below the detection limit during the low-isoflavone diet. F2 isoprostane 8-iso-PGF-2alpha excretion varied widely within and between subjects, and the group mean was not significantly different during the high- and low-isoflavone soy diet (7.67 +/- 1.13 and 8.65 +/- 1.18 nmol/12 h, mean +/- SD, respectively). However, individual changes in 8-iso-PGF-2alpha between the two soymilk drinks were significantly associated with age (r = -0.87; P = 0.006) and several measures of isoflavone exposure, namely, daidzein dose (r = 0.81; P = 0.015), combined daidzein and genistein dose (r = 0.77; P = 0.03), and total urinary excretion of isoflavones (daidzein, genistein, and equol) (r = 0.71; P = 0.05). The findings suggest that soy isoflavones may reduce lipid peroxidation in an age-dependent manner, with greater effects in older women, and with lower doses of isoflavones.

Adult↗
PubMed2004

Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe insulin resistance.

Our objective was to evaluate the effectiveness of the insulin-sensitizing agent rosiglitazone in obese women with polycystic ovary syndrome (PCOS) and severe insulin resistance. Twelve obese women with PCOS were recruited. All were hirsute and anovulatory with acanthosis nigricans indicating severe insulin resistance. All women were treated with 4 mg of rosiglitazone daily for 6 months. A standard 75-g oral glucose tolerance test with insulin levels was performed before and after the women were treated with rosiglitazone. Glucose and insulin areas under the curve (AUC) were calculated. Serum levels of total and free testosterone, dehydroepiandrosterone sulfate, LH, and 17-hydroxyprogesterone were also measured before and after treatment. The body mass index was determined before and after treatment. There was a highly significant (r = 0.881, P < 0.0001) positive correlation between insulin response during oral glucose tolerance test and basal total testosterone levels. After treatment with rosiglitazone, there were significant decreases in fasting insulin levels (46.0 +/- 6.5 vs. 16.9 +/- 2.0 microU/ml; P < 0.001), insulin AUC (749.3 +/- 136.3 vs. 225.0 +/- 15.7 microU/ml; P = 0.003), fasting glucose levels (90.8 +/- 3.0 vs. 81.8 +/- 1.9 mg/dl; P = 0.003), and glucose AUC (437.9 +/- 25.0 vs. 322.5 +/- 14.7 mg/dl; P < 0.001). Both total testosterone (96.3 +/- 17.3 vs. 56.1 +/- 5.8 ng/dl; P = 0.01) and free testosterone (5.8 +/- 0.6 vs. 3.4 +/- 0.5 pg/ml; P < 0.001) decreased significantly after treatment, although there was no significant change in LH levels. Levels of SHBG increased significantly (18.3 +/- 3.4 vs. 25.8 +/- 6.6 nmol/liter; P = 0.009) after treatment, and dehydroepiandrosterone sulfate levels decreased significantly (P = 0.04). There was no significant change in body mass index (40.4 +/- 2.4 vs. 41.1 +/- 2.7 kg/m(2)). Eleven of the women reverted to regular ovulatory cycles during the treatment period. We conclude that 1) rosiglitazone therapy improves insulin resistance and glucose tolerance in obese women with PCOS; 2) rosiglitazone decreases ovarian androgen production, which appears to be independent of any changes in LH levels; 3) hyperinsulinemia appears to play a key role in the overproduction of ovarian androgens in these women because attenuation of insulin levels is associated with decreased testosterone levels; and 4) short-term rosiglitazone therapy helps restore spontaneous ovulation.

Androgens↗
PubMed2003

Efficacy of second versus third generation oral contraceptives in the treatment of hirsutism.

OBJECTIVE: To compare second versus third generation combination oral contraceptives (OCs) in the treatment of hirsutism. METHODS: Women with hirsutism, as defined by a minimum Ferriman-Gallwey score of 10, were randomized in a double-blind fashion to receive an OC containing either ethinyl estradiol/desogestrel or ethinyl estradiol/levonorgestrel for 9 months of treatment. Ferriman-Gallwey scores, androgen levels and sex hormone-binding globulin were measured at baseline and every 3 months for the duration of the study. Hormones were measured in duplicate by radioimmunoassay. RESULTS: Of the 47 women enrolled, 24 were randomized to ethinyl estradiol/desogestrel and 23 were randomized to ethinyl estradiol/levonorgestrel. Mean sex hormone-binding globulin increased significantly in subjects using the desogestrel-containing contraceptive compared with the levonorgestrel-containing contraceptive. Ten subjects completed the 9 months of treatment in the levonorgestrel group and 11 completed the study in the desogestrel group. Mean free testosterone and 3alpha-androstanediol glucuronide decreased significantly in the group receiving ethinyl estradiol/desogestrel but not in the ethinyl estradiol/levonorgestrel group. Mean Ferriman-Gallwey scores decreased significantly in both treatment groups. Improvement in mean Ferriman-Gallwey score was 35.7 +/- 38.1% (p < 0.001) for the ethinyl estradiol/desogestrel arm and 33.4 +/- 27.3% (p < 0.001) for the ethinyl estradiol/levonorgestrel arm. There were no statistically significant differences found in the improvement of Ferriman-Gallwey scores between the two treatment arms, although the power to detect a difference was limited by the small sample size. CONCLUSIONS: Treatment of hirsute women with third generation OCs containing desogestrel results in a significant increase in sex hormone-binding globulin and decrease in free testosterone and 3alpha-androstanediol glucuronide. Both second and third generation OCs were clinically effective in treating hirsutism.

Adolescent↗
PubMed2003

A randomized controlled trial of second- versus third-generation oral contraceptives in the treatment of acne vulgaris.

OBJECTIVE: This study was undertaken to compare the clinical efficacy of second- versus third-generation oral contraceptives in the treatment of acne. STUDY DESIGN: Thirty-four women with acne were randomly selected to receive an oral contraceptive containing 0.3 mg of ethinyl estradiol (EE)/0.15 mg of desogestrel or 0.3 mg of EE/0.15 mg of levonorgestrel for 9 months. Acne was scored by lesion counting by a single examiner, and serum was analyzed for sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and free and total testosterone at baseline and 3-month intervals. RESULTS: At baseline, the two treatment groups did not differ in the mean age, body mass index, acne lesion counts, SHBG, DHEAS, or free and total testosterone. Mean acne lesion counts decreased significantly in both groups from baseline (P <.02). In subjects completing 9 months of therapy, acne decreased by 52.8% in the EE/levonorgestrel group (n = 9) and by 58.5% in the EE/desogestrel group (n = 7) (between groups: P not significant). Mean SHBG increased by 46.3 nmol/L in the EE/desogestrel group (P not significant), and 20.0 nmol/L in the EE/levonorgestrel group (P <.05). Decreases in free testosterone from baseline occurred in each group, but these differences did not reach statistical significance. CONCLUSION: Oral contraceptives containing EE/desogestrel and EE/levonorgestrel were both effective in treating acne.

Acne Vulgaris↗
PubMed2003

Expression of messenger ribonucleic acid encoding steroidogenic enzymes in postmenopausal ovaries.

To investigate expression of steroidogenic enzymes involved in androgen and estrogen synthesis in the stroma of postmenopausal ovaries.Ovarian stromal tissue samples were obtained at hysterectomy from postmenopausal women who had hysterectomy and oophorectomy. Tissues were frozen immediately in liquid nitrogen and kept frozen until RNA was extracted. Total RNA was examined by Northern blot analysis using (32)P-labeled cDNA probes encoding human P450 side chain cleavage (P450(SSC)), P450(17alpha), and cytochrome P450 aromatase (P450(arom)). Concentrations of mRNA encoding cytochrome P450(SSC), cytochrome P450 17alpha-hydroxylase (CYP17), and P450(arom) were determined in the ovarian stroma. We detected P450(SSC) mRNA in all postmenopausal ovaries studied. P450(SSC) mRNA was increased threefold in the ovarian stroma of postmenopausal women with endometrial cancer and endometrial hyperplasia. CYP17 mRNA was detected in the ovarian stroma of all women with endometrial cancer. P450(arom) mRNA was not detected in the ovaries studied. Postmenopausal ovaries possess enzymes for initiation of steroidogenesis. Enzymes essential for androgen synthesis were expressed in the ovarian stroma of postmenopausal women with endometrial cancer or hyperplasia.

Aged↗