Investigation of the metabolism of N, N-Dimethylformamide and its metabolites

The industrial solvent N, N-dimethylformamide (DMF) causes liver damage in humans. The hepatotoxicity of N-alkylformamides seems to be linked to their metabolism to N-alkylcarbamic acid thioesters. To clarify the role of metabolism in DMF hepatotoxicity, the metabolic fate of DMF was investigated in rodents. DMF was rapidly metabolised and excreted in the urine as N-hydroxymethyl-N-methyl-formamide (HMMF), N-acetyl-S-(N-methylcarbamoyl) cysteine (AMCC) and a metabolite measured as formamide by GLC. At high doses (0.7 and 7.0mmo1/kg) a small proportion of the dose was excreted unchanged. AMCC, measured by GLC after derivatisation to ethyl N-methylcarbamate, was a minor metabolite. Only 5.2% of the dose (0.1mmo1/kg) in rats or 1.2% in mice was excreted as AMCC. The minor extent of this metabolic pathway in rodents might account for the marginal liver damage induced by DMF in these species. In a collaborative study, volunteers were shown to metabolise DMF to AMCC to a greater extent than rodents. Nearly 15% of the inhaled dose (0.049mmo1/kg) was excreted as AMCC. This result suggests that the metabolic pathway leading to AMCC is more important in humans than in rodents. Consequently the risk associated with exposure to DMF might be higher in humans than in rodents. The metabolism of formamides to S-(N-alkylcarbamoyl) glutathione, the metabolic precursor of the thioester mercapturates, was studied using mouse, rat and human hepatic microsomes. The metabolism of NMF (10mM) to S-(N-methylcarbanoyl)glutathione (SMG) required the presence of GSH, NADPH and air. Generation of S-(N-methyl-carbamoyl)glutathione (SMG) was inhibited when incubations were conducted in an atmosphere of CO:air (1:1) or when SKF 525-A (3.0mM) was included in the incubations. Pre-treatment of mice with phenobarbitone (PB, 80mg/kg for 4 days) or beta-naphthoflavone (BNF, 50mg/kg for 4 days) failed to increase the microsomal formation of SMG from NMF. This result suggests that the oxidation of NMF is catalysed by a cytochrome P-450 isozyme which is unaffected by PB or BNF. Microsomal incubations with DMF (5 or 10mM) failed to generate measurable amounts of SMG although DMF was metabolised to HMMF. Incubations of microsomes with HMMF resulted in the generation of a small amount of SMG which was affected by inhibitors of microsomal enzymes in the same way as in the case of NMF. HMMF was metabolised to AMCC by rodents in vivo. This result suggests that HMMF is a major intermediate in the metabolic activation of DMF.

How well does the theory of planned behaviour predict alcohol consumption? A systematic review and meta-analysis

This study aimed to quantify correlations between theory of planned behaviour (TPB) variables and (i) intentions to consume alcohol and (ii) alcohol consumption. Systematic literature searches identified 40 eligible studies that were meta-analysed. Three moderator analyses were conducted: pattern of consumption, gender of participants and age of participants. Across studies, intentions had the strongest relationship with attitudes (r+ = .62), followed by subjective norms (r+ = .47) and perceived behavioural control (PBC; r+ = .31). Self-efficacy (SE) had a stronger relationship with intentions (r+ = .48) compared with perceived control (PC; r+ = −.10). Intention had the strongest relationship with alcohol consumption (r+ = .54), followed by SE (r+ = .41). In contrast, PBC and PC had negative relationships with alcohol consumption (r+ = −.05 and −.13, respectively). All moderators affected TPB relationships. Patterns of consumption with clear definitions had stronger TPB relations, females reported stronger attitude–intention relations than males, and adults reported stronger attitude–intention and SE–intention relations than adolescents. Recommendations for future research include targeting attitudes and intentions in interventions to reduce alcohol consumption, using clear definitions of alcohol consumption in TPB items to improve prediction and assessing SE when investigating risk behaviours.

Prevalence of alcohol consumption and pattern of use among the elderly in the WHO European Region

BACKGROUND/AIMS: Alcohol-related problems are relevant in the elderly, particularly in developed countries, but there is a lack of cross-country comparisons. The present work aims to examine the frequency and patterns of alcohol consumption in older adults across different European countries, and to analyze the relationship between socioeconomic status and gender with alcohol consumption. METHODS: General population-based household surveys of randomly selected adults over 60 years of age in 14 European countries. PARTICIPANTS: 10,119 subjects [mean age: 70.4 (SD = 7.1)], 61.9% women. RESULTS: There are marked differences in alcohol consumption across countries. Except for three countries from eastern regions, most people in all countries present moderate consumption regarding the amount of alcohol and pattern of use. However, there are marked gender differences, with a higher intake in men (effect sizes ranging from 0.57 to 1.27), although these differences are relatively proportional across countries. Finally, a higher socioeconomic status is positively related (B = 0.845, 95% CI: 0.30/1.40) with alcohol consumption after controlling for gender, age, health-functioning status and the country's development level. CONCLUSIONS: There are marked differences in consumption of alcohol in the elderly between the different countries, and male gender, as well as a higher SES, were associated with higher alcohol consumption.

Changes in inositol lipids and phosphates after stimulation of the MAS-transfected NG115-401L-C3 cell line by mitogenic and non-mitogenic stimuli

A neuronal cell line (NG115-401L-C3) was stimulated by mitogenic (angiotensin) and non-mitogenic (bradykinin) peptides and examined for the time course of changes in the levels of radiolabelled inositol phosphates and phospholipids. Both peptides stimulated the time-dependent production of Ins(1,4,5)P3 and related metabolites. Bradykinin caused a much larger increase in Ins(1,4,5)P3 than did angiotensin. However, both peptides stimulated similar rises in the levels of Ins(1,3,4)P3 and InsP4. Bradykinin but not angiotensin, caused a rapid (within 2 s) fall in the levels of PtdIns(4,5)P2 and PtdIns(4)P. Serum pretreatment of the cells caused a 2-3-fold potentiation of both the responses to bradykinin and angiotensin. Although significant levels of PtdIns(3)P were detected in resting cells neither mitogenic (angiotensin, insulin-like growth factor I, transforming growth factor beta) nor non-mitogenic (bradykinin, nerve growth factor interleukin-1) receptor activation changed its levels, arguing against regulation of either PtdIns 3-kinase or PtdIns(3)P phosphatase. We conclude that, as judged by the levels of its product. PtdIns(3)P, the enzyme PtdIns 3-kinase is not activated. This questions the significance of this activity in the receptor-mediated initiation of DNA synthesis.

Purification of phosphoric acid by solvent extraction

This work follows a feasibility study (187) which suggested that a process for purifying wet-process phosphoric acid by solvent extraction should be economically viable. The work was divided into two main areas, (i) chemical and physical measurements on the three-phase system, with or without impurities; (ii) process simulation and optimization. The object was to test the process technically and economically and to optimise the type of solvent. The chemical equilibria and distribution curves for the system water - phosphoric acid - solvent for the solvents n-amyl alcohol, tri-n-butyl phosphate, di-isopropyl ether and methyl isobutyl ketone have been determined. Both pure phosphoric acid and acid containing known amounts of naturally occurring impurities (Fe P0 4 , A1P0 4 , Ca3(P04)Z and Mg 3(P0 4 )Z) were examined. The hydrodynamic characteristics of the systems were also studied. The experimental results obtained for drop size distribution were compared with those obtainable from Hinze's equation (32) and it was found that they deviated by an amount related to the turbulence. A comprehensive literature survey on the purification of wet-process phosphoric acid by organic solvents has been made. The literature regarding solvent extraction fundamentals and equipment and optimization methods for the envisaged process was also reviewed. A modified form of the Kremser-Brown and Souders equation to calculate the number of contact stages was derived. The modification takes into account the special nature of phosphoric acid distribution curves in the studied systems. The process flow-sheet was developed and simulated. Powell's direct search optimization method was selected in conjunction with the linear search algorithm of Davies, Swann and Campey. The objective function was defined as the total annual manufacturing cost and the program was employed to find the optimum operating conditions for anyone of the chosen solvents. The final results demonstrated the following order of feasibility to purify wet-process acid: di-isopropyl ether, methylisobutyl ketone, n-amyl alcohol and tri-n-butyl phosphate.

Out in psychology:lesbian, gay, bisexual, trans and queer perspectives

There has been a recent explosion of interest in Lesbian, Gay, Bisexual and Trans Perspective Psychology amongst students and academics, and this interest is predicted to continue to rise. Recent media debates on subjects such as same–sex marriage have fuelled interest in LGBTQ perspectives. This edited collection showcases the latest thinking in LGBTQ psychology. The book has 21 chapters covering subjects such as same sex parenting, outing, young LGBTQ people, sport, learning disabilities, lesbian and gay identities etc. The book has an international focus, with contributors from UK, US, Canada, Australia and New Zealand List of Contributors. Foreword by Jerry J. Bigner. 1. Introducing Out in Psychology (Victoria Clarke and Elizabeth Peel). 2. From lesbian and gay psychology to LGBTQ psychologies: A journey into the unknown (Victoria Clarke and Elizabeth Peel) 3. What comes after discourse analysis for LGBTQ psychology(Peter Hegarty). 4. Recognising race in LGBTQ psychology: Power, privilege and complicity (Damien W. Riggs). 5. Personality, individual differences and LGB psychology (Gareth Hagger Johnson). 6. Heteronormativity and the exclusion of bisexuality in psychology (Meg Barker). 7. A minority within a minority: Experiences of gay men with intellectual disabilities.(Christopher Bennett and Adrian Coyle). 8. Closet talk: The contemporary relevance of the closet in lesbian and gay interaction (Victoria Land and Celia Kitzinger) 9. Romance, rights, recognition, responsibilities and radicalism: Same-sex couples’ accounts of civil partnership and marriage (Victoria Clarke, Carole Burgoyne and Maree Burns). 10. The experience of social power in the lives of trans people (Clair Clifford and Jim Orford). 11. What do they look like and are they among us? Bisexuality, (dis.closure and (Maria Gurevich, Jo Bower, Cynthia M. Mathieson and Bramilee Dhayanandhan). 12. Heterosexism at work: Diversity training, discrimination law and the limits of liberal individualism (Rosie Harding and Elizabeth Peel). 13. Out on the ball fields: Lesbians in sport (Vikki Krane and Kerrie J. Kauer). 14. Homophobia, rights and community: Contemporary issues in the lives of LGB people in the UK (Sonja J. Ellis). 15. Striving for holistic success: How lesbians come out on top (Faith Rostad and Bonita C. Long). 16. On Passing: The Interactional Organization of Appearance Attributions in the Psychiatric Assessment of Transsexual Patients (Susan A. Speer and Richard Green). 17. Alcohol and gay men: Consumption, promotion and policy responses (Jeffrey Adams, Timothy McCreanor and Virginia Braun). 18. Towards a clinical-psychological approach to address the hetero sexual concerns of intersexed women (Lih-Mei Liao). 19. Educational psychology practice with LGB youth in schools: Individual and institutional interventions (Jeremy J. Monsen and Sydney Bailey). 20. Que(e)rying the meaning of lesbian health: Individual(izing and community discourses (Sara MacBride-Stewart). 21. Transsexualism: Diagnostic dilemmas, transgender politics and the future of transgender care (Katherine Johnson). Index.

Chlorhexidine and the prevention of surgical site infection

Surgical site infections (SSI) are a prevalent health care-associated infection (HAl). Prior to the mid-19th century, surgical sites commonly developed postoperative wound complications. It was in the 1860's, after Joseph Lister introduced carbolic acid and the principles of antisepsis that postoperative wound infection significantly decreased. Today, patient preoperative skin preparation with an antiseptic agent prior to surgery is a standard of practice. Povidone-iodine and chlorhexidine gluconate are currently the most commonly used antimicrobial agents used to prep the patient's skin. In this current study, the epidemiology, diagnosis, surveillance and prevention of SSI with chlorhexidine were investigated. The antimicrobial activity of chlorhexidine was assessed. In in-vitro and in-vivo studies the antimicrobial efficacy of 2% (w/v) chlorhexidine gluconate (CHG) in 70% isopropyl alcohol (IPA) and 10% povidoneiodine (PVP-I) in the presence of 0.9% normal saline or blood were examined. The 2% CHG in 70% IPA solutions antimicrobial activity was not diminished in the presence of 0.9% normal saline or blood. In comparison, the traditional patient preoperative skin preparation, 10% PVP-I antimicrobial activity was not diminished in the presence of 0.9% normal saline, but was diminished in the presence of blood. In an in-vivo human volunteer study the potential for reduction of the antimicrobial efficacy of aqueous patient preoperative skin preparations compromised by mechanical removal of wet product from the application site (blot) was assessed. In this evaluation, 2% CHG and 10% povidone-iodine (PVP-I) were blotted from the patient's skin after application to the test site. The blotting, or mechanical removal, of the wet antiseptic from the application site did not produce a significant difference in product efficacy. In a clinical trial to compare 2% CHG in 70% IPA and PVP-! scrub and paint patient preoperative skin preparation for the prevention of SSI, there were 849 patients randomly assigned to the study groups (409 in the chlorhexidine-alcohol and 440 in the povidone-iodine group) in the intention-to-treat analysis. The overall surgical site infection was significantly lower in the 2% CHG in 70% IPA group than in the PVP-I group (9.5% versus 16.1 %, p=0.004; relative risk, 0.59 with 95% confidence interval of 0.41 to 0.85). Preoperative cleansing of the patient's skin with chlorhexidine-alcohol is superior to povidone-iodine in preventing surgical site infection after clean-contaminated surgery.

Mass transfer and chemical reaction on a distillation plate

A multistage distillation column in which mass transfer and a reversible chemical reaction occurred simultaneously, has been investigated to formulate a technique by which this process can be analysed or predicted. A transesterification reaction between ethyl alcohol and butyl acetate, catalysed by concentrated sulphuric acid, was selected for the investigation and all the components were analysed on a gas liquid chromatograph. The transesterification reaction kinetics have been studied in a batch reactor for catalyst concentrations of 0.1 - 1.0 weight percent and temperatures between 21.4 and 85.0 °C. The reaction was found to be second order and dependent on the catalyst concentration at a given temperature. The vapour liquid equilibrium data for six binary, four ternary and one quaternary systems are measured at atmospheric pressure using a modified Cathala dynamic equilibrium still. The systems with the exception of ethyl alcohol - butyl alcohol mixtures, were found to be non-ideal. Multicomponent vapour liquid equilibrium compositions were predicted by a computer programme which utilised the Van Laar constants obtained from the binary data sets. Good agreement was obtained between the predicted and experimental quaternary equilibrium vapour compositions. Continuous transesterification experiments were carried out in a six stage sieve plate distillation column. The column was 3" in internal diameter and of unit construction in glass. The plates were 8" apart and had a free area of 7.7%. Both the liquid and vapour streams were analysed. The component conversion was dependent on the boilup rate and the reflux ratio. Because of the presence of the reaction, the concentration of one of the lighter components increased below the feed plate. In the same region a highly developed foam was formed due to the presence of the catalyst. The experimental results were analysed by the solution of a series of simultaneous enthalpy and mass equations. Good agreement was obtained between the experimental and calculated results.

Predicting binge-drinking behaviour using an extended TPB:examining the impact of anticipated regret and descriptive norms

Aims: To investigate the utility of an extended Theory of Planned Behaviour (TPB), including descriptive norms and anticipated regret, in predicting binge-drinking intentions and behaviour. Methods: A total of178 undergraduates completed a questionnaire containing measures of TPB variables, descriptive norms, anticipated regret, and previous binge-drinking behaviour. One week later, 104 students completed a measure of binge-drinking behaviour. Results: Hierarchical regression demonstrated that attitudes (beta = 0.30, P < 0.001) and anticipated regret (beta = 0.47, P < 0.001) were significant predictors of intentions, with the final equation accounting for 58% of the variance. Hierarchial regression found that intentions (beta = -0.21, P < 0.05) and previous binge-drinking behaviour (beta = 0.36, P < 0.01) predicted current drinking behaviour, accounting for 33% of the variance. Conclusions: The study suggests that modifying attitudes and inducing regret may be effective strategies for reducing binge-drinking intentions among undergraduates, which should reduce subsequent binge-drinking behaviour. © The Author 2006. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved.

The primary amine metabolite of sibutramine stimulates lipolysis in adipocytes isolated from lean and obese mice and in isolated human adipocytes

Sibutramine is a satiety-inducing serotonin-noradrenaline reuptake inhibitor that acts predominantly via its primary and secondary metabolites. This study investigates the possibility that sibutramine and/or its metabolites could act directly on white adipose tissue to increase lipolysis. Adipocytes were isolated by a collagenase digestion procedure from homozygous lean (+/+) and obese-diabetic ob/ob mice, and from lean nondiabetic human subjects. The lipolytic activity of adipocyte preparations was measured by the determination of glycerol release over a 2-hour incubation period. The primary amine metabolite of sibutramine M2, caused a concentration-dependent stimulation of glycerol release by murine lean and obese adipocytes (maximum increase by 157 ± 22 and 245 ± 1696, respectively, p < 0.05). Neither sibutramine nor its secondary amine metabolite M1 had any effect on lipolytic activity. Preliminary studies indicated that M2-induced lipolysis was mediated via a beta-adrenergic action. The non-selective beta-adrenoceptor antagonist propranolol (10-6M) strongly inhibited M2-stimulated lipolysis in lean and obese murine adipocytes. M2 similarly increased lipolysis by isolated human omental and subcutaneous adipocytes (maximum increase by 194 ± 33 and 136 ± 4%, respectively, p < 0.05) with EC50 values of 12 nM and 3 nM, respectively. These results indicate that the sibutramine metabolite M2 can act directly on murine and human adipose tissue to increase lipolysis via a pathway involving beta-adrenoceptors. © Georg Thieme Verlag KG Stuttgart.

Nutritional management of blood glucose levels

Background and Objectives: Nutritional management of blood glucose levels is a strategic target in the prevention and management of type 2 diabetes mellitus (T2DM), applicable across the population. To implement a successful strategy it is essential to understand the impact of dietary modulation on the postprandial rise in blood glucose concentrations. Methods: Using the highest quality data, a systematic and comprehensive literature review was undertaken. Included in this review were the major macronutrients (carbohydrate, pro-tein, fat), micronutrient vitamins and minerals, non-nutrient phytochemicals and additional foods such as low-calorie sweeteners, vinegar and alcohol. Results: The strongest corroboration of efficacy for improving glucose homeostasis was for insoluble and moderately fermentable cereal-based fiber and mono-unsaturated fatty acids as replacement of saturated fat. Postprandial glycaemia was decreased by intake of viscous soluble fiber and the predominant mechanism of action was considered to be by delaying absorption of co-ingested carbohydrates. There was weaker but substantial evidence that certain phytochemical-rich foods were likely to be effective. This may be associated with the su-ggestion that the gut microbiota plays an important role in me-tabolic regulation, which includes provision of phytochemical and other metabolites. Conclusions: Based on the evidence, it is clear that dietary components have significant and clinically relevant effects on blood glucose modulation. This suggests that employing a dietary regimen to attenuate the postprandial rise in blood glucose levels along with previously identified targets (reducing excess body weight and an increase in physical activity) will benefit the health of the population and limit the increasing worldwide incidence of T2D.

Influence of alkyl chain length on sulfated zirconia catalysed batch and continuous esterification of carboxylic acids by light alcohols

The impact of alkyl chain length on the esterification of C2–C16 organic acids with C1–C4 alcohols has been systematically investigated over bulk and SBA-15 supported sulfated zirconias (SZs). Rates of catalytic esterification for methanol with acetic acid are directly proportional to the sulfur content for both SZ and SZ/SBA-15, with the high dispersion of SZ achievable in conformal coatings over mesoporous SBA-15 confering significant rate-enhancements. Esterification over the most active 0.24 mmol gcat−1 bulk SZ and 0.29 mmol gcat−1 SZ/SBA-15 materials was inversely proportional to the alkyl chain length of alcohol and acid reactants; being most sensitive to changes from methanol to ethanol and acetic to hexanoic acids respectively. Kinetic analyses reveal that these alkyl chain dependencies are in excellent accord with the Taft relationship for polar and steric effects in aliphatic systems and the enthalpy of alcohol adsorption, implicating a Langmuir–Hinshelwood mechanism. The first continuous production of methyl propionate over a SZ fixed-bed is also demonstrated.

Using alcohol unit-marked glasses enhances capacity to monitor intake:evidence from a mixed-method intervention trial

AIMS: In the UK, people tend to have poor knowledge of government guidelines for alcohol use, and lack the motivation and skills required to use them to monitor their drinking. The study aim was to determine whether using glasses marked with such guidelines would improve knowledge and attitudes, increase frequency of counting units and lower alcohol intake. METHODS: A total of 450 adults in the UK participated in an intervention vs control study with 1-month follow-up. The intervention group was encouraged to use glasses supplied by the researchers that indicated the unit content of drinks of different strengths and volumes, and stated the intake guidelines. Data were collected online. A further more in-depth interview with 13 intervention group participants enquired into their experiences of using the glasses. RESULTS: Analyses adjusted for baseline variables showed that the intervention improved the following: knowledge of unit-based guidelines, ability to estimate the unit content of drinks, attitudes toward the guidelines and frequency of counting unit intake. However, there was no significant difference in alcohol consumption between the groups at follow-up. Interviews suggested that the glasses encouraged people to think about their drinking and to discuss alcohol with other people. The design of the glasses was not appealing to all, and their initial impact did not always persist. CONCLUSION: Use of unit-marked glasses led to changes in people's reported use of unit-based guidelines to monitor their drinking but, in the short term, no change in consumption. Qualitative data suggested that the glasses could have an impact at the individual level (on knowledge and attitudes) and at a broader level (by prompting discussion of alcohol use).