Differential activation of protein kinase C isoforms by euxanthone,revealed by an in vivo yeast phenotypic assay

The protein kinase C (PKC) modulatory effects of euxanthone, isolated from the wood of Cratoxylum maingayi, on isoforms alpha, betaI, delta, eta and zeta were characterised using an alternative in vivo yeast phenotypic assay. The present study shows that euxanthone can activate isoforms alpha, betaI, delta, eta and zeta, being more effective on PKC-betaI, -delta, -eta and -zeta than the established PKC activators used (the phorbol ester PMA and arachidonic acid for PKC-zeta). Furthermore, euxanthone presents differences on its potency towards individual PKC isoforms, showing a remarkable selectivity for PKC-zeta. These results can help to clarify the molecular basis of the euxanthone-mediated effects.     

Investigation into the significance of task difficulty and divided allocation of resources on the glucose memory facilitation effect

RATIONALE: Memory for a list of 20 words can be enhanced by preceding learning with consumption of 25 g glucose rather than an equally sweet aspartame solution. In previous studies, participants performed a secondary hand-movement task during the list-learning phase. OBJECTIVE: The present placebo-controlled, double-blind study examined whether the additional cognitive load created by a secondary task is a crucial feature of the glucose memory facilitation effect. METHODS: The effect of glucose administration on word recall performance in healthy young participants was examined under conditions where the primary memory task and a secondary task were competing for cognitive resources (across a range of secondary tasks), and where task difficulty was increased but dual task-mediated competition for cognitive resources did not exist. Measures of non-verbal and working memory performance were also compared under the different glycaemic conditions (glucose versus aspartame drinks). RESULTS: In the present study, a beneficial effect of glucose on memory was detected after participants encoded a 20-word list while performing a secondary task, but not when participants encoded the list without a secondary task, nor when the 20 target words were intermixed with 20 non-target words (distinguished by gender of speaker). In addition, glucose significantly enhanced performance on spatial and working memory tasks. CONCLUSION: The data indicate that possible "depletion" of episodic memory capacity and/or glucose-mediated resources in the brain due to performing a concomitant cognitive task might be crucial to the demonstration of a glucose facilitation effect. Possible implications regarding underlying cognitive and physiological mechanisms are discussed in this article.     

Enhanced oxidative stress as a potential mechanism underlying the programming of hypertension in utero

Maternal undernutrition during critical periods of organ development is known to impair fetal growth and predispose to the development of adulthood diseases, such as hypertension, coronary heart disease and type II diabetes that are linked to low birth weight and are characterized by endothelial dysfunction. Increased oxidative stress, in rats submitted to intrauterine undernutrition, provides a potential explanation for the endothelial dysfunction development. The aim of this study was to determine the oxidative stress and its consequence on mesenteric arteriolar responses to vasoactive agents in offspring from diet-restricted dams. For this, female pregnant Wistar rats were fed either normal or 50% of normal intake diets, during the whole gestational period. In male offspring, arterial blood pressure was determined by the tail cuff method in anesthetized rats, mesenteric arteriolar reactivity and superoxide anion generation were studied using intravital microscopy and superoxide dismutase activity was determined in mesentery by spectrophotometric assay. Intrauterine undernutrition induced hypertension, decreased vasodilation to acetylcholine and bradykinin but did not alter the responses to sodium nitroprusside. Topical application of superoxide dismutase and superoxide dismutase mimetic manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin significantly improved the altered arteriolar responses to acetylcholine and bradykinin. A decreased superoxide dismutase activity and an increased superoxide anion concentration were observed in the offspring of diet-restricted dams. This study shows for the first time that intrauterine undernutrition enhances oxidative stress in vivo and relates this to the impaired endothelium-dependent vasodilation.     

Environmental contexts surrounding resolution of drinking problems among problem drinkers with different help-seeking experiences

OBJECTIVE: This study investigated whether similar environmental contexts surround abstinent resolutions associated with different intervention experiences, including no assistance. METHOD: Participants were selected in a 3 x 2 design (25-30 per group, N = 167) according to their help-seeking experiences (no assistance, Alcoholics Anonymous [AA] only, treatment plus AA) and current drinking status (resolved abstinent [RA] for >2 years or nonresolved [NR] controls). Life events were assessed retrospectively over a 4-year period that spanned the 2 years before and 2 years after the initiation of stable abstinence by RA participants or over a matched interval for NR participants. Collateral or reliability interviews were conducted for 84% of the sample as checks on participant reports. RESULTS: Across help-seeking groups, RA participants reported decreased negative events and increased positive events from the pre- through the post-resolution period. Interventions, especially treatment, enhanced the postresolution improvements in RA participants' life circumstances. This pattern was absent among NR participants. CONCLUSIONS: The findings suggest that a similar molar environmental context surrounds resolutions achieved with and without interventions and that interventions are associated with enhanced improvements during maintenance.     

Importance of entero-salivary recirculation in paracetamol pharmacokinetics

The contribution of an entero-salivary recirculation (salivary secretion-swallowed-reabsorption of drug from the gastrointestinal tract) to the values of the pharmacokinetic parameters of paracetamol was studied in a two-way crossover design. Five healthy volunteers took a tablet of Paracetamol (500 mg) in two occasions separated by a washout period. The difference between the two treatments consisted of saliva that was allowed or not to be swallowed during the 4 h of study. No statistically significant differences were found in the values of the pharmacokinetic parameters between treatments. The half-life time calculated from salivary levels was similar to the values previously reported by other authors. The percent of the oral dose excreted in saliva during 4 h of study was very low (0.1%). Secondary peaks appeared in 8 of 10 profiles. The lack of influence of salivary secretion on the pharmacokinetic parameters of Paracetamol and the low percent secreted in this fluid suggests that entero-salivary recirculation is a possible physiological phenomenon undergoing after oral administration, but it is not one of the principal phenomenon that defines the pharmacokinetic of the drug. We confirm that working with salivary samples in pharmacokinetic studies of paracetamol is a useful tool.     

Pharmacokinetics of a novel surface-active agent,purified poloxamer 188, in rat,rabbit, dog and man

Purified poloxamer 188 (PP188) is a non-ionic, block copolymer surfactant that is currently being evaluated clinically in sickle cell disease vaso-occlusive crisis and acute chest syndrome and preclinically in spinal cord injury and muscular dystrophy. This paper describes the pharmacokinetics of PP188 in rats, pregnant rats, pregnant rabbits, dogs and humans. Plasma protein binding interaction studies demonstrated no clinically significant effects on narcotic analgesics, hydroxyurea, warfarin, diazepam or digitoxin, but an increase in free fraction for propranolol. The plasma concentrations increased proportionate with increasing dose in all species tested. Renal clearance accounted for 90% of total plasma clearance in man. A single metabolite was detected and quantified in the plasma from dogs and humans that was cleared more slowly than parent drug. Allometric scaling of plasma clearance and volume of distribution at steady-state (Vss) across species provided good predictions of the pharmacokinetic parameters in humans. Based on the comparative pharmacokinetics of PP188 in rat, rabbit, dog and man, all three animal species were appropriate models for evaluating various aspects of PP188's toxicological profile.     

Helping hospitalised clients quit smoking: a study of rural nursing practice and barriers

ABSTRACT: Brief interventions have been identified as a useful tool for facilitating smoking cessation, particularly in the acute care setting and in areas where access to specialist staff is limited, such as rural Australia. A self-administered survey was used to determine current rural nursing staff practices in relation to brief intervention for smoking cessation, and to ascertain the perceived level of support, skills, needs and barriers amongst these staff to conducting brief interventions. The major findings include that while the majority of respondents were aware of their patients' smoking status, most were not very confident about assisting smoking patients to quit. Casually employed nurses were much less likely to be aware of patient smoking status than nurses employed full-time or permanent part-time. Only one-quarter to one-third of nurses did not believe assisting patients to quit was part of their role, and the vast majority of nurses reported that they were non-smokers. Future programs incorporating the routine use of brief interventions will need to consider these findings.     

Making meaning: the creative component in qualitative research

Findings in qualitative research are often wondrous and exciting, expounding new knowledge and perceptions previously unknown. Qualitative research requires the researcher to ponder and reflect on the data collected so as to find the meaning within. Helping researchers learn how to perform this step is not well discussed in the qualitative literature, yet this is one of the more crucial components of this type of research. In this article, the incubation, the meaning-making phase of qualitative research, is discussed in relation to the experiences of five researchers who have used traditional processes, models, metaphors, plays, pastiche, poetry, and quilt making and design to help them make meaning.