Pharmacological Manipulation of Immune-Induced Food Aversion in Rats

Background: Mice allergic to ovalbumin (OVA) avoid drinking a solution containing this antigen. This was interpreted as related to IgE-dependent mast cell degranulation and sensory C fiber activation. Methods: We employed pharmacological manipulation to further investigate the mediators involved in immune-induced food aversion. Results: While nonimmunized rats preferred a sweetened OVA solution, immunized rats avoided it. We also employed a paradigm in which rats are conditioned to drink water for two 10-min sessions a day. Tolerant rats presented lower IgE titers, and this manipulation abrogated food aversion. Dexamethasone (1.0 mg/kg) prevented the aversion of OVA-immunized rats to the antigen-containing solution. Combined blockade of H(1) and 5-hydroxytryptamine (5-HT)(2) receptors by promethazine (3.0 mg/kg) plus methysergide (5.0 mg/kg) was unable to alter food aversion. Blockade of 5-HT(3) receptors by ondansetron (1.0 mg/kg) caused a twofold increase in the ingestion of the sweetened OVA solution by immunized rats, suggesting the involvement of 5-HT(3) receptors in food aversion. Finally, we showed that dexamethasone or promethazine plus methysergide, but not ondansetron, effectively prevented the IgE-dependent mast-cell-degranulation-induced increase in vascular permeability in rats. Conclusion: We suggest that regardless of whether or not they cause edema, IgE-mediated mast cell degranulation and consequent 5-HT(3) signaling are involved in the process that triggers avoidance to the source of the allergen in allergic rats. Copyright (C) 2008 S. Karger AG, Basel

Alpha-conotoxins: Nicotinic acetylcholine receptor antagonists as pharmacological tools and potential drug leads

Alpha-Conotoxins are small disulfide rich peptides from the venoms of marine cone snails. They target specific nicotinic acetylcholine receptor (nAChR) subtypes with high affinity and potency and are therefore valuable as neurophamacological probes and potential drug leads. This article gives a general overview of the chemical and biological features of alpha -conotoxins, including their pharmacology, binding interactions and structure. A detailed analysis of recently reported three-dimensional structures from members of different subfamilies of the alpha -conotoxins, including those with 3/5, 4/3, 4/6 and 4.7 spacings of their two intracysteine loops is given. The structures are generally well defined and represent useful frameworks for the display of amino acid residues to target molecules.

International childcare practices study: Infant sleeping environment

Background: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. Methods: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to “reduce the risks of SIDS” were available at the time of the survey. Results: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2–88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58–100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. Conclusions: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of “typical” bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Attitudes and practices of general practitioners in the diagnosis and management of attention-deficit/hyperactivity disorder

Objective: To assess understanding of, and actual and potential roles in management of attention-deficit/hyperactivity disorder (ADHD) among GPs. Methods: A cross-sectional questionnaire survey of Queensland GPs selected randomly from the Royal Australian College of General Practitioners directory of members was carried out. Main outcome measures were knowledge levels of ADHD, current management practices, referral patterns and self-perceived information and training needs. Results: Three hundred and ninety-nine GPs returned a completed questionnaire (response rate 76%). Roles identified by GPs were: the provisional diagnosis of ADHD and referral to specialist services for confirmation of the diagnosis and initiation of management; assistance with monitoring progress once a management plan was in place; education of the child and their family regarding the disorder; and liaison with the school where necessary. Perceived barriers to increased involvement of GPs were: time and resource constraints of general practice; concerns regarding abuse and addiction liability of prescription stimulants; complex diagnostic issues associated with childhood behavioural problems; and lack of training and education regarding ADHD. Conclusions: General practitioners identify a role for themselves in ADHD care that is largely supportive in nature and involves close liaison with specialist services.

Amino Acids involved in differences in the pharmacological profiles of the rat and human noradrenaline transporters

It has been suggested from a previous study in our laboratory that differences in the pharmacology of the species variants of the noradrenaline transporter (NET) are the result of four non-conservative amino acid exchanges from the total of 26 amino acids that are divergent between the rat NET (rNET) and human NET (hNET). The aim of this study was to examine the effects of changing the rNET at each of these four amino acid residues, which markedly alter local charge distribution, to the amino acid found in hNET. Site-directed mutagenesis was used to create mutant cDNAs from rNET cDNA. The mutant NETs (rK71), rE62K, rK375N and rR612Q), rNET and hNET were expressed in transiently transfected COS-7 cells to determine the effects of the mutations on the differing pharmacological properties of the species variants. The ratios of V-max for noradrenaline uptake and B-max for nisoxetine binding (which are a measure of the turnover number of the transporter, i.e. the number of transport cycles per min) were greater for rNET and rR612Q than for hNET, rK71), rE62K and rK375N. The K-m of noradrenaline was lower for hNET, rK713, rE62K and rK375N than for rNET or rR612Q. There were no differences between the K-i values for inhibition of noradrenaline uptake by nisoxetine for rNET, hNET or the mutants, but the K-i values of cocaine were lower for hNET, rE62K and rR612Q than rNET or rK375N. Hence, the study showed that: (1) the aspartate 7. lysine 62 and asparagine 375 amino acid residues are important in determining the lower substrate translocation by hNET than rNET; (2) the aspartate 7 and lysine 62 residues in the N-terminus of hNET determine the higher affinities of substrates for the hNET than the rNET; and (3) the lysine 62 and glutamine 612 residues in the N- and C-termini, respectively, of hNET Lire determinants of the higher cocaine affinity for the hNET than rNET.

Practices and attitudes to derivatives use in Australian commonwealth organisations

Little is known about risk management in the public sector This study reports on a survey of senior officers in Australian Commonwealth companies and statutory authorities concerning their practice and attitudes towards the use of derivative instruments for risk management. Using a variety of tests, the most important issue identified by respondents concerning the use of derivatives is for budgeting purposes. Of note, respondents rank commonly cited reasons advanced in the private sector such as reduced bankruptcy costs and taxation, as being relatively unimportant, which is consistent with arguments advanced in the paper The results also indicate that there are significant differences in the level of importance in some issues regarding derivatives use across public sector organisations, particularly those differentiated by a documented risk management plan. The study also documents for the first time the extent of derivatives use in the Australian public sector.