Low to moderate alcohol consumption on serum vitamin D and other indicators of bone health in postmenopausal women in a controlled feeding study.

The objective of this study was to evaluate the effect of 8 weeks of no alcohol, low (1 drink or 15 g/day) and moderate (2 drinks or 30 g/day) alcohol consumption on markers of bone health: fasting serum 25-hydroxy vitamin D (25(OH)D), osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), urine deoxypyridinoline (DPD) and helical peptide (HP) in postmenopausal women (n=51). Compared with no alcohol, 1 or 2 drinks/day for 8 weeks had no significant impact on any of the bone markers. Within each alcohol group, obese women had significantly lower serum 25(OH)D and higher DPD concentrations than normal weight women. Season significantly affected the concentrations of serum 25(OH)D, but there was no significant interaction between alcohol and season on serum 25(OH)D concentrations. Low or moderate alcohol consumption for 8 weeks had no significant impact on markers of bone health in postmenopausal women.

Prediction of formulation effects on dermal absorption of topically applied ectoparasiticides dosed in vitro on canine and porcine skin using a mixture-adjusted quantitative structure permeability relationship.

Topical application of ectoparasiticides for flea and tick control is a major focus for product development in animal health. The objective of this work was to develop a quantitative structure permeability relationship (QSPeR) model sensitive to formulation effects for predicting absorption and skin deposition of five topically applied drugs administered in six vehicle combinations to porcine and canine skin in vitro. Saturated solutions (20 µL) of (14) C-labeled demiditraz, fipronil, permethrin, imidacloprid, or sisapronil were administered in single or binary (50:50 v/v) combinations of water, ethanol, and transcutol (6 formulations, n = 4-5 replicates per treatment) nonoccluded to 0.64 cm(2) disks of dermatomed pig or dog skin mounted in flow-through diffusion cells. Perfusate flux over 24 h and skin deposition at termination were determined. Permeability (logKp), absorption, and penetration endpoints were modeled using a four-term Abrahams and Martin (hydrogen-bond donor acidity and basicity, dipolarity/polarizability, and excess molar refractivity) linear free energy QSPeR equation with a mixture factor added to compensate for formulation ingredient interactions. Goodness of fit was judged by r(2) , cross-validation coefficient, coefficients (q(2) s), and Williams Plot to visualize the applicability domain. Formulation composition was the primary determinant of permeation. Compounds generally penetrated dog skin better than porcine skin. The vast majority of permeated penetrant was deposited within the dosed skin relative to transdermal flux, an attribute for ectoparasiticides. The best QSPeR logKp model for pig skin permeation (r(2) = 0.86, q(2) s = 0.85) included log octanol/water partition coefficient as the mixture factor, while for dogs (r(2) = 0.91, q(2) s = 0.90), it was log water solubility. These studies clearly showed that the permeation of topical ectoparasiticides could be well predicted using QSPeR models that account for both the physical-chemical properties of the penetrant and formulation components.

Assessing resistance against macrocyclic lactones in gastro-intestinal nematodes in cattle using the faecal egg count reduction test and the controlled efficacy test.

The main objective of the present study was to evaluate the accuracy of the faecal egg count reduction test (FECRT) to assess the resistance status of ivermectin (IVM)-resistant isolates of the cattle nematodes Ostertagia ostertagi and Cooperia oncophora, using the controlled efficacy test (worm counts) as a reference. The second objective was to investigate whether both IVM-resistant isolates showed side-resistance against moxidectin (MOX) under controlled conditions. Thirty male Holstein calves were experimentally infected with 25,000 L3 of an IVM-resistant O. ostertagi isolate and 25,000 L3 of an IVM-resistant C. oncophora isolate. Twenty-eight days later the calves were randomly divided into 2 treatment groups and 1 untreated control group. Animals in groups 1 and 2 received MOX (Cydectin(®) 1%, Pfizer) and IVM (Ivomec(®) 1%, Merial) respectively, by subcutaneous injection at a dose rate of 0.2mg/kg bodyweight. Faecal samples were collected 7 and 14 days after treatment and animals were necropsied 14/15 days post-treatment. Both the FECRT and the controlled efficacy test demonstrated that the O. ostertagi and C. oncophora isolates were resistant against IVM, with efficacies below 90%. The IVM-resistant O. ostertagia isolate was still susceptible to MOX treatment, as shown by over 99% reduction in egg counts and worm burden. The FECRT suggested borderline resistance against MOX in the IVM-resistant C. oncophora isolate, with egg count reductions between 97% (95% CI: 76; 100) at day 7 and 86% (95% CI: 49; 96) at day 14. However, the controlled efficacy test clearly showed MOX-resistance, with a decrease of only 31% (95% CI: -12; 57) in C. oncophora worm numbers. After MOX treatment, a significantly lower number of eggs per female C. oncophora worms was counted compared to the control group (43% reduction). Due to this reduced fecundity, the FECRT may fail to detect MOX-resistance.

Moderate alcohol consumption and 24-hour urinary levels of melatonin in postmenopausal women.

CONTEXT: Low overnight urinary melatonin metabolite concentrations have been associated with increased risk for breast cancer among postmenopausal women. The Postmenopausal Women's Alcohol Study was a controlled feeding study to test the effects of low to moderate alcohol intake on potential risk factors for breast cancer including serum and urinary levels of hormones and other biomarkers. Previously, we observed significant increases in concentrations of serum estrone sulfate and dehydroepiandrosterone sulfate in participants after consumption of 15 or 30 g (one or two drinks) of alcohol per day. OBJECTIVE: In the present analysis, we evaluated the relationship of alcohol consumption with 24-h urinary 6-sulfatoxymelatonin (6-SMT) concentration (micrograms per 24 h). DESIGN AND PARTICIPANTS: Healthy postmenopausal women (n = 51) consumed a controlled diet plus each of three treatments (a nonalcoholic placebo beverage or 15 or 30 g alcohol/d) during three 8-wk periods in random order under conditions of weight maintenance. MEASURES: 6-SMT was measured in 24-h urine samples that were collected at entry into the study (baseline) and at the midpoint (4 wk) and end (8 wk) of each of the three diet periods. RESULTS: Concentration of 6-SMT was not significantly modified by the alcohol treatment after adjustment for body mass index, hours of sleep, daylight hours, and baseline level of 6-SMT. CONCLUSIONS: These results suggest that low to moderate daily alcohol consumption does not significantly affect 24-h urinary levels of melatonin among healthy postmenopausal women.

Anti-social behaviour in a large Irish teaching hospital.

BACKGROUND: Anti-social behaviour affects staff physically and psychologically and has financial implications. More information on its occurrence is required for effective risk management. AIMS: We undertook to audit the complete dataset on anti-social behaviour in an urban Irish hospital. METHODS: Data, collected from computerised incident reports between January 2005 and December 2008, were analysed with respect to date, location, incident type, person affected, type and severity of injury. RESULTS: There were 3,727 incidents over 4 years, with numbers rising annually at the approximate rate of 20%. Most involved nursing staff. Incidents occurred primarily on medical and surgical wards and were usually classified as minor. Physical or verbal assaults were most frequently reported. CONCLUSION: Anti-social behaviour appears to be increasing. Certain wards and categories of healthcare professionals are at particular risk. More research is required to explain factors leading to such behaviour and optimum strategies for its active management.

Is dental care utilization associated with oral cavity cancer in a large sample of community-based United States residents?

OBJECTIVES: Cancer of the oral cavity and pharynx remains one of the 10 leading causes of cancer deaths in US. Besides smoking and alcohol consumption, there are no well-established risk factors. While poor dental care had been implicated, it is unknown if lack of dental care, implying poor dental hygiene predisposes to oral cavity cancer. This study aimed to assess the relationship between dental care utilization during the past 12 months and the prevalence of oral cavity cancer. METHODS: A cross-sectional design of the National Health Interview Survey of Adult, noninstitutionalized US residents (n=30 475) was used to assess the association between dental care utilization and self-reported diagnosis of oral cavity cancer. Chi-square statistic was used to examine the crude association between the explanatory variable, dental care utilization and other covariates, while unconditional logistic regression was used to assess the relationship between oral cavity cancer and dental care utilization. RESULTS: There were statistically significant differences between those who utilized dental care during the past 12 months and those who did not with respect to education, income, age, marital status, and gender (P<0.05), but not health insurance coverage (P=0.53). In addition, those who utilized dental care relative to those who did not were 65% less likely to present with oral cavity cancer, prevalence odds ratio (POR), 0.35, 95% confidence interval (CI), 0.12-0.98. Further, higher income, advanced age, people of African heritage, and unmarried status were statistically significantly associated with oral cavity cancer (P<0.05), but health insurance coverage, alcohol use, and smoking were not, P>0.05. After simultaneously controlling for the relevant covariates, the association between dental care and oral cavity cancer did persist but imprecise. Thus, when compared with those who did not use dental care, those who did were 62% less likely to be diagnosed with oral cavity cancer, adjusted POR, 0.38, 95% CI, and 0.13-1.10. CONCLUSIONS: Among US adults residing in community settings, use of dental care during the past 12 months was marginally statistically significantly associated with oral cavity cancer, but clinically relevant in assessing oral cavity cancer prevalence in this sample. However, because of the nature of our data, which restricts temporal sequence, a large sample prospective study that may identify modifiable factors associated with oral cavity cancer development, namely poor dental care is needed.

Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats.

The present study characterizes the safety, pharmacokinetics, and anti-emetic effects of the selective NK-1 receptor antagonist maropitant in the cat. Safety of maropitant was determined following 15 days of subcutaneous (SC) administration at 0.5-5 mg/kg. Maropitant was well tolerated in cats at doses that exceeded the efficacious anti-emetic dose range of the drug by at least a factor of 10 and adverse clinical signs or pathological safety findings were not noted at any dose.The pharmacokinetics of maropitant in cats were determined following single dose oral (PO), intravenous (IV) and SC administration. Maropitant had a terminal half-life of 13-17 h and a bioavailability of 50 and 117% when administered PO and SC, respectively. Efficacy was determined against emesis induced either by xylazine or by motion. A dosage of 1 mg/kg maropitant administered IV, SC or PO prevented emesis elicited by xylazine. The compound had good oral antiemetic activity and a long (24 h) duration of action. Maropitant (1.0 mg/kg) was highly effective in preventing motion-induced emesis in cats. These studies indicate that the NK-1 receptor antagonist maropitant is well tolerated, safe and has excellent anti-emetic properties in cats.

Dietary boron and hormone replacement therapy as risk factors for lung cancer in women.

Hormone replacement therapy (HRT) may reduce lung cancer risk. Dietary boron may have actions similar to those of HRT; however, no previous study has reported the associations between dietary boron intake and lung cancer risk or the joint effects of boron intake and HRT use on lung cancer risk. The authors examined the associations between boron intake and the joint effects of boron intake and HRT on lung cancer risk in women. In an ongoing case-control study in Houston, Texas (July 1995 through April 2005, end date for this analysis), 763 women were diagnosed with lung cancer, and 838 were matched healthy controls with data on both diet and HRT. Multiple logistic regression analyses were conducted to assess the associations between dietary boron and HRT with lung cancer risk. After adjustment for potential confounders, the odds ratios for lung cancer with decreasing quartiles of dietary boron intake were 1.0, 1.39 (95% confidence interval (CI): 1.02, 1.90), 1.64 (95% CI: 1.20, 2.24), and 1.95 (95% CI: 1.42, 2.68) mg/day, respectively, for all women (p(trend) < 0.0001). In joint-effects analyses, compared with women with high dietary boron intake who used HRT, the odds ratio for lung cancer for low dietary boron intake and no HRT use was 2.07 (95% CI: 1.53, 2.81). Boron intake was inversely associated with lung cancer in women, whereas women who consumed low boron and did not use HRT were at substantial increased odds.

Measures of adiposity and body fat distribution in relation to serum folate levels in postmenopausal women in a feeding study.

OBJECTIVE: To assess the associations between serum folate concentration and measures of adiposity in postmenopausal women. DESIGN: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n=51) consumed 0 g (control), 15 g (one drink) and 30 g (two drinks) alcohol (ethanol)/day for 8 weeks as part of a controlled diet. Subjects in one treatment arm were crossed-over to another arm after a 2- to 5-week washout period. Body mass index (BMI) was measured, and dual energy X-ray absorptiometry (DEXA) scan administered to the women during the control (0 g alcohol) treatment, and a blood sample from this group was collected at baseline and week 8 of each diet period and analyzed for folate, B12, homocysteine and methylmalonic acid. SETTING: This study was conducted at the Beltsville Human Nutrition Research Center, MD, USA. RESULTS: In multivariate analysis, women who were overweight had a 12% lower, and obese women had a 22% lower serum folate concentrations compared to normal weight women (P-trend=0.02). Vitamin B12 also decreased with increasing BMI (P-trend=0.08). Increased BMI, percent body fat, and absolute amounts of central and peripheral fat were all significantly associated with decreased serum folate, but were unrelated to serum B12, homocysteine or methylmalonic acid. CONCLUSIONS: Our data show that adiposity is associated with lower serum folate levels in postmenopausal women. With obesity at epidemic proportions, these data, if confirmed by prospective or randomized controlled studies, have important public health implications.

Calorie intake misreporting by diet record and food frequency questionnaire compared to doubly labeled water among postmenopausal women.

OBJECTIVE: We assessed the extent of energy misreporting from the use of a self-administered 7-day diet record (7-DDR) and a widely used food frequency questionnaire (FFQ) compared to total energy expenditure from doubly labeled water (DLW) in a group of postmenopausal women. DESIGN: At baseline, 65 healthy postmenopausal women were instructed to fill out the National Cancer Institute's (NCI) FFQ and a 7-DDR. Average total energy expenditure using the DLW method was also performed at baseline. RESULTS: On average, the women underestimated total energy intake compared to total energy expenditure assessed from DLW by 37% on the 7-DDR and 42% on the FFQ. CONCLUSIONS: These findings suggest that the interpretation of findings from the 7-DDR- and FFQ-based energy-disease association studies in postmenopausal women needs further evaluation. SPONSORSHIP: This research was supported (in part) by the Intramural Program of the NIH (National Cancer Institute).

No association between alcohol supplementation and autoantibodies to DNA damage in postmenopausal women in a controlled feeding study.

Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used.

Estimating the relative risk of developing melanoma in INK4A carriers.

Estimation of the relative risk of cancer due to rare germline mutations using population-based epidemiological techniques is challenging, since studies with very large numbers of subjects are required. In this pilot study using a novel study design, we evaluated the role of INK4A mutations in melanoma by comparing patients with multiple primary melanomas to those with single primaries. Patients were ascertained from the Surgery and Dermatology Clinics at Memorial Sloan-Kettering Cancer Center and at the Yale University Pigmented Lesion Clinic. Subjects completed a questionnaire covering risk factors for melanoma and were tested for INK4A mutations. Five (8%) of 65 patients with multiple primaries had a mutation, compared with none of 88 patients with single primaries (P=0.03). Examination of other factors, such as number of nevi on the arms of the patients, fair skin, hair and eye colour, and other phenotypic characteristics associated with the risk of melanoma, demonstrates that these factors exhibit higher prevalence in the multiple primary cases than in the single primaries. These results provide evidence of the utility of the new study design in evaluating the impact of rare but highly penetrant cancer risk factors.

Randomized, placebo-controlled trial of dietary supplementation of alpha-tocopherol on mutagen sensitivity levels in melanoma patients: a pilot trial.

We evaluated the effects of vitamin E (dl-alpha-tocopherol) on mutagen sensitivity levels in a randomized placebo-controlled pilot trial. In brief, a dietary supplement of 1000 mg/day vitamin E or a placebo was randomly administered for 3 months to melanoma outpatients clinically free of the disease. Plasma vitamin E and mutagen sensitivity levels were measured at baseline and at the end of the trial after 3 months. At baseline, we found no significant differences in plasma vitamin E and mutagen sensitivity levels between the two groups. We also measured dietary intake at baseline and found dietary vitamin E to be a poor predictor of plasma levels of vitamin E. After 3 months of supplementation, we found that plasma levels of alpha-tocopherol increased significantly (P = 0.0005) in the vitamin E compared to the placebo group. We also found a non-significant, but consistent decrease in plasma gamma-tocopherol concentrations in the vitamin E supplemented compared to the placebo group. We did not find any significant difference between the vitamin E and placebo groups in mutagen sensitivity levels either at baseline or after 3 months of supplementation. We conclude that short term vitamin E supplementation, although it causes increased blood levels of alpha-tocopherol, does not provide protection against bleomycin-induced chromosome damage.

Alpha-tocopherol dietary supplement decreases titers of antibody against 5-hydroxymethyl-2'-deoxyuridine (HMdU).

This study evaluated the effects of vitamin E (alpha-tocopherol) on oxidative DNA damage in a randomized double-blind Phase II chemoprevention trial. Oxidative DNA damage was measured by the level of auto-antibody (Ab) against 5-hydroxymethyl-2'-deoxyuridine (HMdU) in plasma. After the baseline screening, eligible subjects (n = 31; plasma samples from 28 subjects were available for this study) were randomized to receive 15, 60, or 200 mg of alpha-tocopherol per day for 28 days. Biomarkers were measured twice at baseline--on day 1 (visit 1) and day 3 (visit 2)--and twice after intervention--on day 17 (visit 3) and day 31 (visit 4). At baseline, there was a highly significant inverse correlation between anti-HMdU Ab titer and plasma vitamin E level (r = -0.53; P = 0.004; n = 28). Smoking did not affect baseline anti-HMdU Ab titer; however, anti-HMdU Ab titer levels at baseline were significantly lower in subjects with above-median (0.75 ounce/day) alcohol consumption (P = 0.008). No significant change in anti-HMdU Ab level occurred at either visit 3 or visit 4 for subjects on the lowest dose, 15 mg alpha-tocopherol per day. Subjects receiving 60 mg of alpha-tocopherol per day had a significant decrease in anti-HMdU Ab level at visits 3 and 4 compared with baseline (P = 0.049 and P = 0.02, respectively). However, subjects receiving the highest dose, 200 mg/day, had less consistent results: a significant decrease in anti-HMdU Ab level was seen at visit 4 (P = 0.04) but not at visit 3. Our results demonstrate an inverse relationship between alpha-tocopherol and anti-HMdU Abs in plasma; oxidative DNA damage can be modulated by short-term dietary supplementation of alpha-tocopherol in some subjects.

Effects of dietary supplementation of alpha-tocopherol on plasma glutathione and DNA repair activities.

In a randomized double-blind trial of alpha-tocopherol (vitamin E), we investigated the effects of alpha-tocopherol supplementation on lipid- and water-soluble antioxidants in plasma and DNA repair activities in peripheral mononuclear leukocytes. Baseline levels of antioxidants and DNA repair activities were assessed twice before alpha-tocopherol intervention: on day 1 (visit 1) and day 3 (visit 2). During the second visit, participants were randomized to receive one of three dosages of alpha-tocopherol, 15, 60, or 200 mg/day for 4 weeks. The same biochemical measurements as at baseline were repeated twice after intervention: on day 17 (visit 3) and day 31 (visit 4). A total of 31 healthy volunteers were eligible for the study, completed all four visits and were included in the final data analysis. At baseline, no appreciable differences of dietary intake of vitamin E and plasma alpha-tocopherol were observed among the three dosage groups. In general, supplementation of alpha-tocopherol for 2-4 weeks resulted in a dose-dependent increase of plasma level of alpha-tocopherol (compared to baseline); significant increases of plasma alpha-tocopherol at visits 3 and 4 were observed in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. At visit 4 (but not visit 3), plasma glutathione levels were significantly elevated (compared to baseline) in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In addition, there was an increase in the lipid protection ratio by supplementation of alpha-tocopherol for 2-4 weeks in the two higher dosage groups, 60 and 200 mg, but not in the lowest dosage group, 15 mg. In general, there were no consistent effects of alpha-tocopherol on DNA repair activities in peripheral mononuclear leukocytes after being adjusted for baseline DNA repair activities. Results from this study demonstrate the interrelationship between alpha-tocopherol and other antioxidants in plasma; total plasma antioxidants can be modulated by short-term dietary supplementation of alpha-tocopherol.

The Tobago leg of the Intersalt Study: urine sodium, bloodpressure and body mass index correlations - abstract

Tobago is a participant in the INTERSALT study, a multicentre study of inter-relationships between salt intake, bloodpressure and other variables. In the period 1986-1987, in Tobago, a random sample of 200 men and women, 25 in each of 8 age/sex groups, were enrolled in the study. Systolic and diastolic bloodpressure levels were measured with a Hawksley random sphygmomanometer under defined conditions, a spot urine and 24-hr. urine collection were obtained and information was obtained on cardio-vascular risk factors (questionnaire), drug schedules and alcohol intake. Overall in the INTERSALT study of 52 centres in 32 countries, increase of systolic and diastolic bloodpressure with age was significantly related to the average sodium excretion. In addition, sodium excretion (positive), body mass index (positive), heavy alcohol intake (positive) and potassium excretion (negative) were significantly related to the bloodpressure of individuals. In Tobago, prevalence of raised bloodpressure was 18 per cent. Thirteen per cent of men were heavy drinkers (>300 ml alcohol per week), and an average body mass index of 27.0 (kg/m2) and sodium/potassium ratio 2.77 were recorded (men and women combined). The results indicate above optimal values of these variables in Tobago, and suggest the potential for appropriate lifestyle changes of high bloodpressure in Tobago (AU)