Vitamin C intake and apoptosis in normal rectal epithelium.

Apoptosis, or programmed cell death, may lower the risk of neoplasia by removing genetically damaged or mutated cells. A high rate of apoptosis has been linked to a reduced risk of colorectal adenomas; therefore, it is important to understand factors that impact apoptosis. Antioxidants (e.g., vitamin C) protect cells from harmful oxidation processes but may interfere with apoptosis by protecting genetically damaged cells from reactive oxygen species-dependent cell death. The objective of this study was to evaluate the association between vitamin C intake and apoptosis in normal rectal mucosa. Study participants were part of a large, cross-sectional study, the Diet and Health Study III. Participants were recruited from consecutive, consenting patients who underwent colonoscopy at University of North Carolina Hospitals between August 1, 1998 and March 4, 2000. Vitamin C intake, obtained from a food frequency questionnaire, included both dietary sources and vitamin supplements. Apoptosis was measured by morphological evaluation of H&E-stained sections obtained from pinch biopsy samples of normal rectal mucosa in consenting participants (n = 503). The relationship between vitamin C and apoptosis varied by adenoma status. Among individuals with adenomas, there was an inverse linear association between apoptosis and total vitamin C intake. Similarly, individuals with adenomas in the highest quintile of total vitamin C intake were substantially less likely than those in the lowest quintile to have increased colonic apoptosis (odds ratio, 0.05; 95% confidence interval, 0.01-0.46). Vitamin C was not significantly associated with apoptosis in adenoma-free patients. High vitamin C intake was associated with reduced colorectal apoptosis among individuals with adenomas in this study population. Given that high apoptosis may lower colorectal cancer risk, vitamin C supplements may be contraindicated for patients with a history of adenomas.     

Changes in rapidly extracted auditory evoked potentials during tracheal intubation

BACKGROUND: One of the problems encountered in assessment of the hypnotic level during anesthesia is the extraction of a consistent and reliable measure online and close to real time. Hemodynamic parameters such as heart rate and blood pressure are not, at least with the traditional single parameter versus time presentation, adequate for ensuring an optimal level of anesthesia, especially when using neuromuscular blocking agents (NMBA). In the literature, it has been demonstrated that auditory evoked potentials (AEP) are able to provide two aspects relevant to determining level of anesthesia: firstly, they have identifiable anatomical significance and, secondly, their characteristics reflect the way the brain perceives a stimulus. METHODS: The aim of this study was to evaluate the AEP index based on a system identification model, the autoregressive model with exogenous input (ARX-model), and to compare it to the classical method, the moving time average (MTA). The ARX enables the extraction within 15-25 sweeps, depending on the signal-to-noise ratio (SNR), whereas MTA typically needs 250-500 sweeps. The hypothesis of the present study was that since the ARX-model extracts the AEP faster than the MTA-model, the former should be able to detect changes during the brief, intense stimulus of endotracheal intubation. Twelve female patients scheduled for gynecological surgery were included in the study. Anesthesia was initiated with thiopentone and maintained with isoflurane and alfentanil. The AEP was mapped into an index (AEP-index) normalized to 100 when the individual was awake and decreasing to an average of 25 during thiopentone induced anaesthesia. The results were compared to those obtained by MTA-extracted AEP. RESULTS: During tracheal intubation 9 patients showed an increase in the ARX-extracted AEP-index larger than 15, and 6 of these patients showed an increase larger than 25 (mean increase=33, SD=18). The MTA-extracted AEP-index showed only one patient with an increase larger than 15. The ARX-extracted AEP changed significantly faster than the MTA-extracted AEP. CONCLUSION: The ARX-extracted AEP-index increases during tracheal intubation. There is a significant difference between the ARX-extracted AEP and the traditional MTA-extracted AEP, in terms of response time. In order to trace short-lasting changes in the hypnotic level by AEP, the AEP should be extracted by a method with a fast response such as the ARX-model.     

Evidence that atrazine and diaminochlorotriazine inhibit the estrogen/progesterone induced surge of luteinizing hormone in female Sprague-Dawley rats without changing estrogen receptor action.

High oral doses of atrazine (ATRA) disrupt normal neuroendocrine function, resulting in suppression of the luteinizing hormone (LH) surge in adult, ovariectomized (OVX) estrogen-primed female rats. While the mechanism by which ATRA inhibits LH secretion is not known, current data indicate that ATRA does have anti-estrogenic properties in vitro and in vivo. In the body, ATRA is rapidly converted to diaminochlorotriazine (DACT). The present study was conducted to investigate the effects of ATRA and DACT on the estradiol benzoate (EB)/progesterone (P) induced LH surge and to determine if such changes correlate with impaired estrogen receptor (ER) function. ATRA, administered by gavage for five consecutive days to adult OVX, female Sprague-Dawley rats, caused a dose-dependent suppression of the EB/P induced LH surge. Although to a lesser degree than ATRA, DACT significantly suppressed total plasma LH and peak LH surge levels in EB/P primed animals by 60 and 58%, respectively. DACT treatment also decreased release of LH from the pituitary in response to exogenous gonadotropin releasing hormone (GnRH) by 47% compared to control. Total plasma LH secretion was reduced by 37% compared to control, suggesting that in addition to potential hypothalamic dysfunction, pituitary function is altered. To further investigate the mechanism by which hypothalamic function might be altered, potential anti-estrogenicity of ATRA and DACT were assessed by evaluating ER function treated rats. Using an in vitro receptor binding assay, ATRA, but not DACT, inhibited binding of [(3)H]-estradiol to ER. In contrast, ATRA, administered to female rats under dosing conditions which suppressed the LH surge, neither changed the levels of unoccupied ER nor altered the estrogen induced up-regulation of progesterone receptor mRNA. Collectively, these results indicate that although ATRA is capable of binding ER in vitro, the suppression of LH after treatment with high doses of ATRA is not due to alterations of hypothalamic ER function.     

The SF-36 health status questionnaire in assessing patients with epistaxis secondary to hereditary hemorrhagic telangiectasia

BACKGROUND: This study assesses the ability of the short form 36 (SF-36), a validated health status survey, to measure the health of patients with epistaxis due to hereditary hemorrhagic telangiectasia (HHT). METHODS: Thirty-eight patients completed the SF-36 and symptom-specific questionnaires. They were asked to rate their epistaxis as severe, moderate, or mild. The SF-36 data are compared with a reference population and analyzed with respect to the subgroups. RESULTS: The scores for each dimension of health were significantly reduced (p < 0.05) when compared with the reference population for all dimensions except pain. When compared with the patients' ratings of severity, a significant correlation was detected in five dimensions (p < 0.05). CONCLUSION: The SF-36 reflects the reduced health status of patients with epistaxis due to HHT. Changes in the SF-36 score could be used as an outcome measure in assessing efficacy of treatment of this condition.     

A prospective study of body size in different periods of life and risk of premenopausal breast cancer.

The prevalence of obesity at all ages is increasing epidemically worldwide. Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce. In 1991 to 1992, a prospective cohort study was assembled in Norway and Sweden. We included in the analysis presented here 99,717 premenopausal women. During the follow-up period, which ended in December 1999, 733 of these women developed a primary invasive breast cancer. Overweight and obesity [body mass index (BMI) > 25 kg/m(2)] at enrollment was associated with a decreased risk of premenopausal breast cancer (P for linear trend = 0.007). Apparent associations between perceived body shape at age 7 and BMI at age 18, with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk, lost their statistical significance after adjustment for BMI at cohort enrollment. Body size at age 7 was correlated with BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48). Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk. Height was related to risk, with a statistically significantly 30% reduced risk only in women shorter than 160 cm as compared with taller ones. The decreased risk of premenopausal breast cancer was observed in overweight and obese women without, but not in those with, a family history of breast cancer.     

Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

OBJECTIVES: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. STUDY DESIGN: Thirty-six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17beta-estradiol (17beta-E(2)), SoyLife 150 or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension recordings. Concentration response curves to carbamylcholine chloride, sodium nitroprusside (SNP) and l-NAME were evaluated after precontraction with potassium. Total RNA was extracted, reverse transcribed and eNOS quantitated by real-time polymerase chain reaction (real-time PCR). RESULTS: Plasma cholesterol was significantly higher at termination in the SoyLife group (P<0.0001), whereas low-density lipoprotein (LDL) cholesterol was comparable in all treatment groups. Neither treatment influenced the endothelium-dependent responses to carbamylcholine chloride or l-NAME or the endothelium-independent response to SNP in any of the arteries. Correspondingly, eNOS mRNA was similarly expressed in all treatment groups in both arteries. CONCLUSIONS: Improvement of cerebral endothelial function by estrogen or soy isoflavones in ovariectomized WHHL rabbits is not supported by the present data. The findings may be unique to the WHHL rabbit in which the hypocholesterolemic effect of estrogens mediated by upregulation of liver LDL receptors is excluded.     

Ascorbinsäure,ein Vorstadium des C-Vitamins. II

Zusammenfassung Es wird eine Mikromethylenblaumethode zur quantitativen Bestimmung der Serumascorbinsäure mitgeteilt.Durch vergleichende Untersuchungen mitLund undLiecks Methylenblaumethode wird die Auffassung bekräftigt, daß die Ascorbinsäure ein Vorstadium des C-Vitamins ist.