Circulating triacylglycerol and apoE levels in response to EPA and docosahexaenoic acid supplementation in adult human subjects

High doses of n-3 PUFA found in fish oils can reduce the circulating concentration of triacylglycerol (TG), which may contribute to the positive impact of these fatty acids on the risk of CVD. The present study aimed to establish the differential impact of EPA and docosahexaenoic (DHA) on plasma lipids and apo in adults. Forty-two normolipidaemic adult subjects completed a double-blind placebo controlled parallel study, receiving an EPA-rich oil (4.8 g EPA/d), DHA-rich oil (4.9 g DHA/d) or olive oil as control, for a period of 4 weeks. No effects of treatment on total cholesterol, LDL-cholesterol or HDL-cholesterol were evident. There was a significant 22 % reduction in TG level relative to the control value following the DHA treatment (P=0.032), with the 15 % decrease in the EPA group failing to reach significance (P=0.258). There were no significant inter-group differences in response to treatment for plasma apoA1, -C3 or -E levels, although a significant 15 % within-group increase in apoE was evident in the EPA (P=0.006) and DHA (P=0.003) groups. In addition, a within-group decrease in the apoA1:HDL-cholesterol ratio was observed in the DHA group, suggesting a positive impact of DHA on HDL particle size. The DHA intervention resulted in a significant increase in the proportion of EPA P=0.000 and DHA P=0.000 in plasma phospholipids, whilst significant increases in EPA P=0.000 and docosapentaenoic acid P=0.002, but not DHA P=0.193, were evident following EPA supplementation (P<0.05). Our present results indicate that DHA may be more efficacious than EPA in improving the plasma lipid profile.     

An increase in reactive oxygen species by dietary fish oil coupled with the attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte apoptosis

We showed previously that the dietary combination of fish oil, rich in (n-3) fatty acids, and the fermentable fiber pectin enhances colonocyte apoptosis in a rat model of experimentally induced colon cancer. In this study, we propose that the mechanism by which this dietary combination heightens apoptosis is via modulation of the colonocyte redox environment. Male Sprague-Dawley rats (n = 60) were fed 1 of 2 fats (corn oil or fish oil) and 1 of 2 fibers (cellulose or pectin) for 2 wk before determination of reactive oxygen species (ROS), oxidative DNA damage, antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)] and apoptosis in isolated colonocytes. Fish oil enhanced ROS, whereas the combination of fish oil and pectin suppressed SOD and CAT and enhanced the SOD/CAT ratio compared with a corn oil and cellulose diet. Despite this modulation to a seemingly prooxidant environment, oxidative DNA damage was inversely related to ROS in the fish oil and pectin diet, and apoptosis was enhanced relative to other diets. Furthermore, apoptosis increased exponentially as ROS increased. These results suggest that the enhancement of apoptosis associated with fish oil and pectin feeding may be due to a modulation of the redox environment that promotes ROS-mediated apoptosis.     

Temporal and spatial variability in the estrogenicity of a municipal wastewater effluent

The estrogenicity of a municipal wastewater effluent was monitored using the vitellogenin biomarker in adult male fathead minnows (Pimephales promelas). The variability in the expression of vitellogenin was evident among the monitoring periods. Significant (alpha< or =0.05) increases in plasma vitellogenin concentrations were detected in March and December, but not in August or June. Additionally, the magnitude of expression was variable. Variability in the spatial scale was also evident during the March and June exposure months. Concurrent exposures in both the creek receiving the effluent from a wastewater treatment plant and an experimental wetland showed estrogenicity to be different with distance from the respective effluent inflow sites. March exposures showed estrogenicity to be somewhat persistent in the receiving creek (>600 m), but to decrease rapidly within the experimental wetland (<40 m). Results are discussed relative to the monitoring season, to the spatial distribution of the response in both receiving systems, and to possible causative factors contributing to the effluent estrogenicity.     

In vitro and in vivo characterization of a novel naphthylamide ATP-sensitive K+ channel opener, A-151892

1. Openers of ATP-sensitive K(+) channels are of interest in several therapeutic indications including overactive bladder and other lower urinary tract disorders. This study reports on the in vitro and in vivo characterization of a structurally novel naphthylamide N-[2-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-naphthalen-1-yl]-acetamide (A-151892), as an opener of the ATP-sensitive potassium channels. 2. A-151892 was found to be a potent and efficacious potassium channel opener (KCO) as assessed by glibenclamide-sensitive whole-cell current and fluorescence-based membrane potential responses (-log EC(50)=7.63) in guinea-pig bladder smooth muscle cells. 3. Evidence for direct interaction with KCO binding sites was derived from displacement of binding of the 1,4-dihydropyridine opener [(125)I]A-312110. A-151892 displaced [(125)I]A-312110 binding to bladder membranes with a -log Ki value of 7.45, but lacked affinity against over 70 neurotransmitter receptor and ion channel binding sites. 4. In pig bladder strips, A-151892 suppressed phasic, carbachol-evoked and electrical field stimulus-evoked contractility in a glibenclamide-reversible manner with -log IC(50) values of 8.07, 7.33 and 7.02 respectively, comparable to that of the potencies of the prototypical cyanoguanidine KCO, P1075. The potencies to suppress contractions in thoracic aorta (-log IC(50)=7.81) and portal vein (-log IC(50)=7.98) were not substantially different from those observed for suppression of phasic contractility of the bladder smooth muscle. 5. In vivo, A-151892 was found to potently suppress unstable bladder contractions in obstructed models of unstable contractions in both pigs and rats with pED(35%) values of 8.05 and 7.43, respectively. 6. These results demonstrate that naphthylamide analogs exemplified by A-151892 are novel K(ATP) channel openers and may serve as chemotypes to exploit additional analogs with potential for the treatment of overactive bladder and lower urinary tract symptoms.     

Synthesis and structure-activity relationships of a novel series of tricyclic dihydropyridine-based KATP openers that potently inhibit bladder contractions in vitro

Structure-activity relationships were investigated on a novel series of tricyclic dihydropyridine-containing K(ATP) openers. This diverse group of analogues, comprising a variety of heterocyclic rings fused to the dihydropyridine nucleus, was designed to determine the influence on activity of hydrogen-bond-donating and -accepting groups and their stereochemical disposition. Compounds were evaluated for K(ATP) activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a subset of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation.     

Estimated blood alcohol concentration correlation with self-reported negative consequences among college students using alcohol

OBJECTIVE: The estimated blood alcohol concentration (eBAC) is a potentially useful index of alcohol-induced intoxication and impairment. This study investigates the association of the eBAC with negative consequences associated with alcohol use. METHOD: Self-reported negative consequences were assessed using a stratified random sampling of 4,708 undergraduate students at a public university with a total enrollment of 12,550. Survey questions permitted the calculation of the "typical" eBAC for each respondent. The eBACs were correlated with demographic characteristics and self-reported negative consequences. The effectiveness of eBAC in predicting negative consequences was compared with drinks per week and consumption at or above the heavy episodic drinking level by calculating receiver operator characteristic values and incremental validity through multiple logistic regressions. RESULTS: The odds of reporting a higher eBAC were significantly elevated for men, underage underclassmen and members of Greek organizations. The odds of reporting a negative consequence were highly associated with each incremental increase in the eBAC. In correlating with negative consequences, the performance of the eBAC index was not significantly different from drinks per week and the heavy episodic drinking index. CONCLUSIONS: As an index of alcohol consumption, the "typical" eBAC is correlated with 17 self-reported social and health consequences. There are potential advantages in using the eBAC index for assessing alcohol use among college drinkers.     

A randomized, controlled comparison of the efficacy and tolerability of low and high doses of haloperidol in the treatment of first-episode psychosis

While haloperidol is still widely used in the treatment of psychoses, the optimal daily dose remains a topic of controversy, particularly in first-episode psychosis. Previous studies have suggested that doses as low as 2 mg/d may be effective, whereas others have indicated superiority for higher over lower doses. This double-blinded, randomized controlled study compared the efficacy and tolerability of 2 vs. 8 mg/d of haloperidol over 6 wk in 40 subjects with first-episode psychosis. Both treatments were equally effective in reducing the PANSS Total and subscale scores. The low dose of haloperidol was better tolerated, with fewer extrapyramidal side-effects, less frequent use of anticholinergic medication and smaller elevations in prolactin levels. Using a low dose of haloperidol is at least as effective as, and better tolerated than a high dose of haloperidol in the treatment of first-episode psychosis.     

Evaluation and comparison of commercially available Aloe vera L. products using size exclusion chromatography with refractive index and multi-angle laser light scattering detection

Raw materials supplied as Aloe vera L. (sometimes referred to as Aloe barbadensis) samples often contain different composition of low and high molecular weight components when analyzed by size exclusion chromatography. One major reason for variable compositions of commercial A. vera L. materials is that they are produced by different manufacturing techniques. Consistent composition of matter based upon a given standard has been difficult to define. In addition, the method of quantifying and characterization of these commercially available materials has not been agreed upon within the industry. The end user, whether a researcher, a manufacturer, a marketing arm of industry or the consumer, should know that they are receiving a consistent product. A blind study of 32 various A. vera L. samples from different manufacturers, and a prepared sample of fresh A. vera L. gel with the commercial, biologic drug Acemannan Immunostimulanttrade mark, were analyzed for content of high molecular weight (polysaccharides) material by size exclusion chromatography with refractive index detection (SEC/RI) and SEC/RI coupled with multi-angle laser light scattering (MALLS) detection. Results from the SEC/RI analysis showed significant variation in the high molecular weight content, and the MALLS analysis also showed significant variation versus SEC/RI. In addition, HPLC analysis of the anthraquinone content showed that all samples contained significantly less than that of the raw, unwashed aloe gel. The variation of results from all analysis is attributed to differing methods in which the samples were processed by the different manufacturers.     

Estimating the survival benefits gained from providing national cancer genetic services to women with a family history of breast cancer

The aim of this paper is to compare a service offering genetic testing and presymptomatic surveillance to women at increased risk of developing breast cancer with its predecessor of no service at all in terms of survival and quality-adjusted survival (QALYs) by means of a Markov cohort chain simulation model. Genetic assessment and presymptomatic care provided between 0.07-1.61 mean additional life years and 0.05-1.67 mean QALYs over no services. Prophylactic surgery and surveillance extended mean life expectancy by 0.41-1.61 and 0.32-0.99 years, respectively over no services for high-risk women. Model outcomes were sensitive to all the parameters varied in the sensitivity analysis. Providing cancer genetic services increase survival and as long as services do not induce adverse psychological effects they also provide more QALYs. The greatest survival and QALY benefits were found for women with identified mutations. As more cancer genes are identified, the survival and cost-effectiveness of genetic services will improve. Although mastectomy provided most additional life years, when quality of life was accounted for oophorectomy was the optimal strategy. Delayed entry into coordinated genetic services was found to diminish the average survival and QALY gains for a woman utilising these services.     

Sun exposure may protect against non-Hodgkin lymphoma: a case-control study

Ultraviolet radiation is a hypothesised risk factor for non-Hodgkin lymphoma (NHL) but no epidemiological study has examined this association using direct measures of sun exposure in individuals. Adults aged 20-74 years living in NSW and ACT, Australia, were the study population. Cases (704 of 829 invited to take part, 85%) were diagnosed January 2000 to August 2001. Controls (694 of 1,136 invited to take part, 61%) were randomly selected from state electoral rolls and frequency-matched to cases by age, sex and state of residence. A self-administered questionnaire and telephone interview measured outdoor hours on working and nonworking days and vacations at 10, 20, 30, 40, 50 and 60 years of age. Logistic regression models of NHL and sun exposure contained the 3 matching variables, ethnicity and sun sensitivity measures as covariates. Contrary to expectations, risk of NHL fell with increasing reported sun exposure hours. Relative to 1.0 for the lowest quarter of total sun exposure hours, the odds ratios (ORs) for successively higher quarters were 0.72 (95% CI 0.53-0.98), 0.66 (0.48-0.91) and 0.65 (0.46-0.91) (p(trend)=0.01). The association of sun exposure on nonworking days with NHL was stronger; OR for highest quarter 0.47 (0.34-0.66) (p(trend)=0.0001). Risk also fell with sun exposure on vacations; OR for highest quarter 0.60 (0.43-0.85) (p(trend)=0.003). These associations appeared strongest in women and in childhood. There was little evident trend in risk with exposure on working day. Our results provide strong statistical evidence for an inverse association between sun exposure and NHL. Increasing evidence that vitamin D may protect against cancer makes UV-mediated synthesis of vitamin D a plausible mechanism whereby sun exposure might protect against NHL.