Identification of equivalent residues in the gamma, delta, and epsilon subunits of the nicotinic receptor that contribute to alpha-bungarotoxin binding

Cysteine was introduced from residues 116 to 121 of the gamma subunit of the fetal mouse acetylcholine receptor, and the mutant receptors were treated with methanethiosulfonate reagents and examined for changes in ligand binding properties. Of the 18 combinations of mutant and reagent, only receptors harboring gammaL119C treated with the quaternary ammonium reagent MTSET (trimethylammonium-ethyl methanethiosulfonate) show a decreased number of alpha-bungarotoxin (alpha-btx) sites. The decrease of 50% suggests that alpha-btx binding to the site harboring gammaL119C is blocked. Analysis of binding of the site-selective ligands dimethyl-d-tubocurarine (DMT) and alpha-conotoxin M1 (CTX) confirm specificity of modification for the site harboring gammaL119C. Cysteines placed at equivalent positions of the delta and epsilon subunits also lead to selective loss of alpha-btx binding following MTSET treatment. gammaL119C receptors treated with the primary amine reagent MTSEA (aminoethyl methanethiosulfonate) retain alpha-btx binding to both sites but show reduced affinity for DMT and CTX at the modified site. Lysine mutagenesis of Leugamma119, Leudelta121, and Leuepsilon119 mimics MTSEA treatment, whereas mutagenesis of Thralpha119 and Glnbeta119 is without effect, demonstrating subunit and residue specificity of MTSEA modification. MTSET modification of nearby gammaY117C does not block alpha-btx binding but markedly diminishes affinity for DMT and CTX. The overall findings indicate a localized point of interaction between alpha-btx and the modified gammaL119C, deltaL121C, and epsilonL119C.     

Do spatial skills contribute to sex differences in different types of mathematical problems?

A battery consisting of spatial tests from the Kit of Factor-Referenced Cognitive tests, a linguistic test, and mathematical tests covering a wide exploratory collection of problems was administered to 262 female and 314 male students in Grades 10 and 12 to examine the relationship between sex differences on particular spatial tests and sex differences on particular mathematical problems. In general, the magnitude of the sex difference on any mathematical problem was not diminished when spatial and linguistic scores were taken into account. This finding was observed in the context of sex differences in most of the spatial tests and in the linguistic test. A difference in the direction and size of the sex difference as a function of the type of mathematical problem was also observed. Females performed better than males on logical, relatively abstract problems. Males demonstrated greater mastery of proportionality, scale, and 2- and 3-dimensional problems. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial

OBJECTIVE: To test the hypothesis that ibuprofen increases the risk of hospitalization for gastrointestinal bleeding, renal failure, or anaphylaxis among febrile children. DESIGN: Randomized double-blind acetaminophen-controlled trial. SETTING: Outpatient pediatric and family medicine practices. PATIENTS: A total of 84,192 children. INTERVENTION: Patients were randomly assigned to receive 12 mg/kg of acetaminophen, 5 mg/kg of ibuprofen, or 10 mg/kg of ibuprofen. MAIN OUTCOME MEASURES: Hospitalizations for acute gastrointestinal bleeding, acute renal failure, and anaphylaxis. RESULTS: A total of 277 patients (0.3%) were unavailable for follow-up. Overall, 795 participants (1%) were hospitalized, primarily for infectious diseases; hospitalization rates did not differ according to treatment group. Four children had diagnoses of acute, nonmajor gastrointestinal bleeding (two in each ibuprofen dosage group); among ibuprofen-treated children, the observed risk of gastrointestinal bleeding, 7.2 per 100,000 (95% confidence interval, 2 to 18 per 100,000), was not significantly different from the risk among acetaminophen-treated children (P = .31). There were no hospitalizations for acute renal failure or anaphylaxis; the upper 95% confidence bound for the risk of either of these outcomes was 5.4 per 100,000 ibuprofen-treated children. Among a number of other possibly serious adverse drug events, low white blood cell count was marginally associated with ibuprofen treatment. Because this association was observed in the setting of multiple comparisons and white blood cell counts may have been low before treatment, causation is unclear. CONCLUSIONS: The risk of hospitalization for gastrointestinal bleeding, renal failure, or anaphylaxis was not increased following short-term use of ibuprofen in children. These data, however, provide no information on the risks of less severe outcomes or the risks of prolonged ibuprofen use.