Children's beliefs about drinking

This paper reports the results of a study in which age (grade level), racial/ethnic, and gender differences in beliefs and perceived norms about drinking were examined in a multi-ethnic urban sample of 4th through 7th grade children. Results showed that older children held beliefs and perceived norms that were more favorable toward drinking than younger children. The major difference between older and younger children lay in their differential estimates of the likelihood of certain consequences occurring and not in their evaluation of these consequences of drinking. Further, older children not only displayed less motivation to comply with their parents and greater motivation to comply with their peers, but they also perceived their parents, as well as their peers, as less disapproving of drinking than did younger children. There were few gender or race/ethnicity differences at these ages in children's beliefs and perceived norms about drinking.     

Pharmacological modulation of endothelial function by insulin in the rat aorta

The aim of this study was to investigate the transdermal iontophoresis of a newly designed capsaicin derivative, sodium nonivamide propionate (SNP). The iontophoretic permeation of SNP from various pH buffers increased following the decrease of pH values. This trend was consistent with that of sodium nonivamide acetate (SNA) which is another synthetic analogue of capsaicin. However, the iontophoretic permeability of SNP was much lower than that of SNA. SNP was also delivered iontophoretically from hydrogel formulations. It is suggested that ionizable polymers should be avoided for iontophoretic delivery to maintain good penetration capacity of drugs. Both nonionic cellulose polymers of methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) showed higher iontophoretic flux for SNP than the others did. Furthermore, the flux of SNP leveled off with an increase in the amount of polymers in hydrogel, indicating that the viscosity of vehicles plays an important role in the permeation of SNP. Comparing the various iontophoretic application modes, the discontinuous on/off cyclic mode showed higher penetration capacity than did the continuous mode although they possessed the same electrical energy. Moreover, the desorption time of SNP from skin was approximately 20 min which was longer than that of SNA.     

Driveway crush injuries in young children: a highly lethal, devastating, and potentially preventable event

BACKGROUND/PURPOSE: The aim of this study was to investigate driveway-related injuries in children, identify associated risk factors, and evaluate outcome compared with other mechanisms of blunt trauma. METHODS: A 6-year review (1991 to 1996) of pediatric (age less than 18 years) pedestrian injuries treated at two urban trauma centers was conducted: one regional pediatric trauma center and one level I trauma center with pediatric commitment. Five hundred twenty-seven children injured in pedestrian accidents were identified from the trauma registry; 51 children (10%) sustained traumatic injuries as a result of being struck in their driveway. Data are reported as mean +/- SEM. RESULTS: Children less than 5 years of age (n = 41) had an injury severity score (ISS) of 12.3+/-2.3, 15 (37%) sustained closed head injury, 13 (37%) had torso trauma, 19 (46%) skeletal trauma, and eight (20%) died. Children > or = 5 years old (n = 10) had an ISS of 10.7+/-2.4, three (30%) sustained closed head injury, four (40%) torso trauma, six (60%) skeletal trauma, and none died. In contrast, all other pediatric pedestrian accidents analyzed over the same time period had a mortality rate of only 2% (11 of 476). CONCLUSIONS: Pediatric driveway trauma carries a significant risk of head injury and a 10-fold increase in mortality in children under 5 years of age when compared with all other pediatric pedestrian accidents. More emphasis must be placed on injury prevention and public education to prevent this devastating mechanism of injury in these young, vulnerable children.     

Design, synthesis, and conformational analysis of a novel series of HIV protease inhibitors

A combination of structure-based design and both solution, and solid-phase synthesis were utilized to derive a potent (nM) series of HIV-1 protease inhibitors bearing a structurally novel backbone. Detailed structural analysis of several inhibitors prepared in this series has suggested that rigidification of the P1/P2 region of this class of molecules may result in compounds with improved potency.     

Noncanonical conformation of nucleic acids: structure with slipped-loops, occurring in DNA oligonucleotides

A HPLC method was developed and validated for the quantitation of 9-cis-retinoic acid (ALRT1057) and its major metabolite, 4-oxo-9-cis-retinoic acid (LG100182) in human plasma. Samples were buffered and extracted with methyl-tert-butyl-ether. The analytes and an I.S. were separated on a C18 HPLC column using a shallow gradient of 70-89% organic solvent. The analytes were quantitated by UV detection at 348 nm. Selectivity against endogenous compounds and potential metabolites (retinol, all trans-, 13-cis-, and 4-hydroxy-9-cis-retinoic acid) was demonstrated. The run time was 29 min. The standard curve was linear from 2.5 to 450 ng ml-1. Interassay precision for both analytes in quality control samples was less than 5.0% RSD. Accuracy was within 11.0% RE for both compounds. Analyte stability during sample storage, extraction processing, and chromatography was established. Method ruggedness was tested by two analysts and on two HPLC systems. This method has been applied to the quantitation of clinical samples.     

Interneuronal frontal-amygdala interactions in cats trained for the quality of the reinforcement

In eight cats the appetitive instrumental conditioned reflexes to light were elaborated by the method of "active choice" of reinforcement quality: the short-latency bar-pressing responses were reinforced with bread-meat mixture and the delayed responses were reinforced with meat. The animals differed in behavior strategy: six cats preferred the delayed pressings (the so-called "self-control" group), and two cats preferred the pressings with short delay (the so-called "impulsive" group). The multiunit activity in the basolateral amygdala and frontal cortex was recorded by chronically implanted nichrome semimicroelectrodes. The interactions of the neighboring neurons in the basolateral amygdala and the frontal cortex (within the local neuronal networks) and between the amygdalar and cortical neurons (distributed neuronal networks of amygdalar-frontal and fronto-amygdalar directions) were estimated by means of statistical crosscorrelation analysis of spike trains. The interneuronal cross-correlations were studied with delays in the range of 0-100 ms. The number of cross-correlations between the neuronal discharges both in the local and distributed networks was significantly higher in "impulsive" cats, mainly, with delays in the range of 0-30 ms. In both groups of animals the number of correlations was the highest during omissions of conditioned pressings, i.e., in cases of difficult choice of reinforcement. We suggest that the basolateral amygdala, frontal cortex, and amygdalar-frontal distributed neuronal networks are involved in the system of brain structures, which determine the individual features of animal behavior.     

Inactivity of N229A thymidylate synthase due to water-mediated effects: isolating a late stage in methyl transfer

Mutation of thymidylate synthase N229(177) to alanine results in an essentially inactive enzyme, yet it leads to formation of a stable ternary complex. The kinetics of N229(177)A show that kcat for Escherichia coli is reduced by 200-fold while the Km for dUMP is increased 200-fold and the Km for folate increased by tenfold versus the wild-type enzyme. The crystal structures of N229(177)A in complex with dUMP and CB3717, and in complex with dUMP alone are determined at 2.4 A, and 2.5 A resolution. These structures identify the covalently bound ternary complex and show how N229(177)A traps an intermediate, and so becomes inactive in a later step of the reaction. Since the smaller alanine side-chain at N229(177)A does not directly sterically impair binding of ligands, the structures implicate, and place quantitative limits on the involvement of the structured water network in the active site of thymidylate synthase in both catalysis and in determining the binding affinity for dUMP (in contrast, the N229(177)V mutation in Lactobacillus casei has minimal effect on activity).     

Sequential assignment of 1H, 15N, 13C resonances and secondary structure of human calmodulin-like protein determined by NMR spectroscopy

Human calmodulin-like protein (CLP) is closely related to vertebrate calmodulin, yet its unique cell specific expression pattern, overlapping but divergent biochemical properties, and specific target proteins suggest that it is not an isoform of calmodulin. To gain insight into the structural differences that may underlie the difference target specificities and biochemical properties of CLP when compared to calmodulin, we determined the sequential backbone assignment and associated secondary structure of 144 out of the 148 residues of Ca2+-CLP by using multinuclear multidimensional NMR spectroscopy. Despite a very high overall degree of structural similarity between CLP and calmodulin, a number of significant differences were found mainly in the length of alpha-helices and in the central nonhelical flexible region. Interestingly, the regions of greatest primary sequence divergence between CLP and calmodulin in helices III and VIII displayed only minor secondary structure differences. The data suggest that the distinct differences in target specificity and biochemical properties of CLP and calmodulin result from the sum of several minor structural and side-chain changes spread over multiple domains in these proteins.