Behavioral and biochemical correlates of chronic administration of quipazine

In Experiment 1 groups of rats received single injections of 1, 3, 10, 20 or 40 mg/kg quipazine, and their total 24-hr food and water intake after a 24-hr deprivation period was recorded; there was a dose-related reduction of both food and water intake. In Experiment 2 a group of 15 rats received 5 mg/kg/day, SC quipazine during 29 days, and a control group received saline injections. During treatment, all animals were exposed to a 24-hr food and water deprivation schedule, alternated with 24 hr of free access. Food and water consumption was measured 2 and 24 hr after drug injection; regional 5-HT concentrations were determined at 1 and 13 treatment days by fluorometric assay. Beginning the first treatment day, food and water intake decreased, but by the 13th day the quipazine group had returned to normal ingestion levels. 5-HT concentrations were increased in cerebellum and cortex in acute conditions, but after 13 days they had decreased in cerebellar samples. In Experiment 3 we found that the effects of quipazine on food and water ingestion were recovered after 14 days of discontinuing chronic drug administration.     

Negative regulation of FcepsilonRI signaling by FcgammaRII costimulation in human blood basophils

BACKGROUND: Signaling through the antigen receptors of human B and T cells and the high-affinity IgE receptor FcepsilonRI of rodent mast cells is decreased by cross-linking these receptors to the low-affinity IgG receptor FcgammaRII. The inhibition is thought to involve the tyrosine phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the FcgammaRIIB cytoplasmic tail, creating binding sites for SH2-containing protein (Src homology domain containing protein tyrosine phosphatase 1 and 2 [SHP-1, SHP-2]) and/or lipid (SH2 domain-containing polyphosphatidyl-inositol 5-phosphatase) phosphatases that oppose activating signals from the costimulated antigen receptors. OBJECTIVE: In human basophils and mast cells FcepsilonRI signaling generates mediators and cytokines responsible for allergic inflammation. We proposed to determine whether FcepsilonRI signaling is inhibited by FcgammaRII costimulation in human basophils and to explore the underlying mechanism as an approach to improving the treatment of allergic inflammation. METHODS: FcgammaR expression on human basophils was examined using flow cytometry and RT-PCR analysis. FcgammaRII/FcepsilonRI costimulation was typically accomplished by priming cells with anti-dinitrophenol (DNP) IgE and anti-DNP IgG and stimulating with DNP-BSA. Phosphatases were identified by Western blotting, and their partitioning between membrane and cytosol was determined by cell fractionation. Biotinylated synthetic peptides and phosphopeptides corresponding to the FcgammaRIIB ITIM sequence were used for adsorption assays. RESULTS: We report that peripheral blood basophils express FcgammaRII (in both the ITIM-containing FcgammaRIIB and the immunoreceptor tyrosine-based activation motif-containing FcgammaRIIA forms) and that costimulating FcgammaRII and FcepsilonRI inhibits basophil FcepsilonRI-mediated histamine release, IL-4 production, and Ca(2+) mobilization. The inhibition of basophil FcepsilonRI signaling by FcgammaRII/FcepsilonRI costimulation is linked to a significant decrease in Syk tyrosine phosphorylation. Human basophils express all 3 SH2-containing phosphatases. CONCLUSIONS: Evidence that FcgammaRII/FcepsilonRI costimulation induces SHP-1 translocation from the cytosolic to membrane fractions of basophils and that biotinylated synthetic peptides corresponding to the phosphorylated FcgammaRIIB ITIM sequence specifically recruit SHP-1 from basophil lysates particularly implicates this protein phosphatase in the negative regulation of FcepsilonRI signaling by costimulated FcgammaRII.     

A diary approach to analysing young adults' drinking events and motivations

Completing a diary over two weeks, 201 young adults recorded each of their drinking events, and information about the context and their motivations for alcohol use. Males reported almost twice as many drinking events and three times the number of drinks over the two-week period. At the same time, males and females mostly drank from Wednesdays to Sundays, with the majority of beer, wine and spirit consumption being between 4 p.m. and midnight. Most drinking occurred in mixed-sex peer groups, and the next greatest in family gatherings. Males mostly drank beer, while females chose either wine or spirits. Most drinking was in bars or at home. Males tended to drink for a wider range of reasons. The advantages of using prospective diaries in studies of young adults' alcohol use are discussed.     

Effect of television advertising of alcohol on alcohol consumption and intentions to drive

The alcohol consumption of 120 male and female college students was measured as they viewed a 90-min videotape of popular prime-time television programmes. Independent measures were the sex of the student, their drinker classification (light or moderate-heavy) and the number of alcohol advertisements (0, 6, 12) shown during the screening of the television programmes. Dependent measures were the number of drinks consumed, and the intentions of students to drive a motor vehicle after viewing the videotaped programmes. As predicted, males consumed more alcohol than females, and moderate-heavy drinkers consumed more than light drinkers. Male and female students who viewed six alcohol advertisements consumed more alcohol than students shown no alcohol advertisements or 12 alcohol advertisements. Analysis of intentions to drive after viewing the programmes revealed that the number of drinks consumed was not a significant covariate of driving intentions. Rather light drinkers of both sexes were less likely to intend to drive than moderate-heavy drinkers. Males exposed to alcohol advertisements were less likely to intend to drive than males who did not view alcohol advertisements. Different levels of exposure to alcohol advertisements did not influence the driving intentions of college females.     

Diclofenac‐induced pseudoporphyria; an under‐recognized condition?

Pseudoporphyria is a photodistributed bullous disorder that is clinically and histologically similar to porphyria cutanea tarda (PCT), but without abnormal porphyrin biochemistry. Renal failure, dialysis, excessive ultraviolet A and medications, particularly nonsteroidal anti‐inflammatory drugs (NSAIDs), have been associated with pseudoporphyria. We report a case of diclofenac‐induced pseudoporphyria in a man with psoriatic arthritis. To our knowledge, this is only the second reported case of pseudoporphyria associated with diclofenac. Diclofenac has hitherto been considered by many dermatologists as a safe alternative in NSAID‐induced pseudoporphyria.