Southeast Asians: Asian-Pacific Americans at risk for substance misuse

Projections indicate that by the year 2000 over a million Cambodians, Laotians, and Vietnamese will be living in the United States. There is sparse information relative to the use of substances by these groups due to the absence of national prevalence data. The combined stressors that these refugee groups have faced puts them at high risk for substance misuse. Southeast Asians infrequently use substance misuse and mental health services, which has been perceived as a lack of need for services by these groups. In reality, there is a critical shortage of culturally-appropriate treatment and intervention programs as the prevalence of substance misuse increases in these populations.     

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.     

Non-extraction therapy in maxillary deficiency cases

Combined orthodontic and surgical management of maxillary deficiency with a Class III profile has accomplished efficient treatment and predictable results. Also, orthodontic/orthopedic therapy can give good results; but, in any case, if one of either or a combined therapy is selected, the orthodontist has to be sure of the correct diagnosis. The cephalometric analyses have to be done with care as it is possible to find contradictions among different analyses, especially in the A/P aspect. The Wits appraisal shows good capacity for determining the antero-posterior maxillomandibular relationship because it is sensitive to the osseous dimensional variants and lower anterior facial height. Nevertheless, it is a supplementary evaluation requiring additional data for the localization of the deformity.     

Evidence for a functional role of the dynamics of glycine-121 of Escherichia coli dihydrofolate reductase obtained from kinetic analysis of a site-directed mutant

Two-dimensional heteronuclear (1H-15N) nuclear magnetic relaxation studies of dihydrofolate reductase (DHFR) from Escherichia coli have demonstrated that glycine-121 which is 19 A from the catalytic center of the enzyme has large-amplitude backbone motions on the nanosecond time scale [Epstein, D. M., Benkovic, S. J., and Wright, P. E. (1995) Biochemistry 34, 11037-11048]. In order to probe the dynamic-function relationships of this residue, we constructed a mutant enzyme in which this glycine was changed to valine. Equilibrium binding studies indicated that the Val-121 mutant retained wild-type binding properties with respect to dihydrofolate and tetrahydrofolate; however, binding to NADPH and NADP+ was decreased by 40-fold and 2-fold, respectively, relative to wild-type DHFR. Single-turnover experiments indicated that hydride transfer was reduced by 200-fold to a rate of 1.3 s-1 and was the rate-limiting step in the steady state. Interestingly, pre-steady-state kinetic analysis of the Val-121 mutant revealed a conformational change which preceded chemistry that occurred at a rate of 3.5 s-1. If this step exists in the kinetic mechanism of the wild-type enzyme, then it would be predicted to occur at a rate of approximately 2000 s-1. Glycine-121 was also changed to alanine, serine, leucine, and proline. While the Ala-121 and Ser-121 mutants behaved similar to wild-type DHFR, the Leu-121 and Pro-121 mutants behaved like Val-121 DHFR in that hydride transfer was the rate-limiting step in the steady state and a conformational change preceding chemistry was observed. Finally, insertion of a glycine or valine between amino acids 121 and 122 produced mutant enzymes with properties similar to wild-type or Val-121 DHFRs, respectively. Taken together, these results provide compelling evidence for dynamic coupling of a remote residue to kinetic events at the active site of DHFR.