Effect of ethanol on toxicity and metabolism of amphetamine in the mouse.

Ethanol, 3 g/kg i.p., did not significantly alter the acute toxicity of amphetamine in the mouse. However, the urinary metabolite pattern was changed, suggesting that ethanol suppressed metabolism of the stimulant during the initial 6 h period. After 24 h, the mouse metabolized the same fraction of a given dose of amphetamine, whether it was given as amphetamine alone or amphetamine mixed with 2,3 or 4 g/kg ethanol.     

Research and Reflection: Potential Impact on the Professional Development of Undergraduate Occupational Therapy Students

In occupational therapy education in South Africa, community service (CS) focuses learning opportunities during fieldwork placements. CS therefore enabled the researcher to utilise successive small scale research projects to guide learning of students during fieldwork while simultaneously developing the occupational therapy service at a residential care facility. This community setting provided a powerful environment through which research, in combination with opportunities for reflection, contributed to nurturing skills needed by these future health professionals. A technical action research (AR) approach incorporated AR cycles and opportunities for structured reflection. Therefore situations were created for the students to embrace experiential learning. Experiential learning in the form of anticipatory reflection, reflection-in-action, reflection on reflection and retrospective reflection impacted on the quality of the students’ work. Besides encouraging unique leaning opportunities for students when engaging in research during their fieldwork placement, engagement in AR cycles simultaneously improved service delivery to residents in the facility. Key benefits of this investigation were that fieldwork education utilising AR cycles within a CS situation promoted students to identify voids in their theoretical background as well as practice skills; to apply reflective practice that could contribute to their personal and professional development; and to utilize learning opportunities optimally. Despite positive gains showed by this study, the role of power relations between the researcher as fieldwork educator and the students prohibited the AR cycles from being more emancipatory in nature and should be addressed in follow-up studies.     

An improved branch-and-bound algorithm to minimize the weighted flowtime on identical parallel machines with family setup times

This article investigates identical parallel machines scheduling with family setup times. The objective function being the weighted sum of completion times, the problem is known to be strongly NP-hard. We propose a constructive heuristic algorithm and three complementary lower bounds. Two of these bounds proceed by elimination of setup times or by distributing each of them to jobs of the corresponding family, while the third one is based on a lagrangian relaxation. The bounds and the heuristic are incorporated into a branch-and-bound algorithm. Experimental results obtained outperform those of the methods presented in previous works, in term of size of solved problems.     

Children's family change: reports and records of mothers, fathers and children compared

Family change, when adults depart or arrive around children, raises policy issues. Its measurement depends upon the evidence collected and from whom. This paper compares British children's histories obtained from fathers and mothers. The evidence, on one birth cohort of parents, comes from two sources: the National Child Development Study and the ONS Longitudinal Study. The resulting account of family change is not substantially different between parents. There is some under-reporting of children not living with their fathers. This is due to under-reporting by those included in the studies and to under-representation in them of absent fathers and lone parents.     

Cellular responses to mild heat stress

Since its discovery in 1962 by Ritossa, the heat shock response has been extensively studied by a number of investigators to understand the molecular mechanism underlying the cellular response to heat stress. The most well characterized heat shock response is induction of the heat shock proteins that function as molecular chaperones and exert cell cycle regulatory and anti-apoptotic activities. While most investigators have focused their studies on the toxic effects of heat stress in organisms such as severe heat stress-induced cell cycle arrest and apoptosis, the cellular response to fever-ranged mild heat stress has been rather underestimated. However, the cellular response to mild heat stress is likely to be more important in a physiological sense than that to severe heat stress because the body temperature of homeothermic animals increases by only 1–2°C during febrile diseases. Here we provide information that mild heat stress does have some beneficial role in organisms via positively regulating cell proliferation and differentiation, and immune response in mammalian cells.Received 14 May 2004; received after revision 2 August 2004; accepted 16 August 2004     

Human peripheral blood monuclear cells transfected with messenger RNA stimulate antigen-specific cytotoxic T-lymphocytes in vitro

The efficiency of test vaccines needs to be evaluated by quantification of the triggered cellular immune response. Usually, for these assays, autologous target cells expressing the vaccine antigen are required. In the context of messenger RNA (mRNA)-based vaccinations, the target cells used for the read-out are mRNA-transfected monocyte-derived dendritic cells (Mo-DCs). Their production typically requires samples of 100 ml blood from the patients, and limits the number of assays that can be performed. We show here that fresh peripheral blood mononuclear cells (PBMCs) can be transfected with mRNA by electroporation. Such cells are as efficient as mRNA-transfected Mo-DCs for their ability to activate memory T cells in vitro. Thus, mRNA-transfected PBMCs are a convenient replacement of mRNA-transfected Mo-DCs for the in vitro monitoring of natural or vaccine-induced immune responses.Received 17 February 2005; received after revision 1 May 2005; accepted 7 Juni 2005     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005     

Leptin receptor action and mechanisms of leptin resistance

The adipose tissue-derived hormone leptin regulates energy balance and neuroendocrine function. Resistance to the appetite-suppressing effects of leptin is associated with common forms of obesity. Here, we review the mechanisms by which leptin activates intracellular signals and the roles that these signals play in leptin action in vivo. Furthermore, we discuss potential mechanisms of leptin resistance, specifically focusing on data regarding the neuroanatomical locus of leptin resistance and potential mechanisms by which expression of the suppressor of cytokine signaling-3 may impair leptin action.Received 30 September 2004; received after revision 12 November 2004; accepted 23 November 2004