Using sobriety tests to increase awareness of alcohol impairment

There is a need to investigate methods by which drinkers canbe made aware of their level of alcohol impairment prior todriving. In the current research, 195 students at various bloodalcohol concentration (BAC) levels participated in an evaluationof three simple sobriety tests: a ruler drop/reaction time task,a balance test and a verbal task. Although self-reported measuresof impairment were the best predictors of BAC, both the rulerdrop and body balance tests accounted for significant portionsof BAC variance. These tasks were also perceived by the studentsas reflecting substantial driving ability. Unfortunately, asBAC increased, poor test performance was less likely to resultin a decision not to drive. These results are discussed in termsof the need to continue studying ways to educate drinkers abouttheir level of alcohol impairment so that they can make informeddrinking/driving decisions.     

Microsomal UDP-glucuronyltransferase-catalyzed bilirubin diglucuronide formation in human liver

Human liver microsomal bilirubin UDP-glucuronyltransferase catalyzes formation of bilirubin mono- and diglucuronide. KmUDPGA and Vmax of the enzyme are 0.6 mM and 1.69 nmol/mg protein X min. In vitro, bilirubin readily dissolves in the microsomal lipid phase. Taking this into account a Kmbilirubin of 60.6 microM was found, which is much higher than the in vivo microsomal UCB concentration of human liver (2.9-11.4 microM). The total capacity of human liver to form bilirubin mono- and diglucuronide in vitro exceeds the in vivo mono- and diglucuronide production rates by a factor 8 to 10. Radiation-inactivation studies reveal that human liver microsomal bilirubin UDP-glucuronyltransferase is a tetrameric enzyme with a molecular mass of 209 000 +/- 20 000 Da. The complete tetrameric enzyme catalyzes both glucuronidation steps, formation of bilirubin monoglucuronide and conversion of mono- to diglucuronide. In its monomeric form, the enzyme with molecular mass of 55 000 +/- 1 500 Da catalyzes only the first step of bilirubin glucuronidation, the formation of bilirubin monoglucuronide.     

Carnitine deficiency associated with ornithine transcarbamylase deficiency

An infant with X-linked recessive ornithine transcarbamylase deficiency is described who also had severe deficiency of plasma and liver carnitine during normoammonemic periods. Treatment with L-carnitine (100 mg/kg/day) for 12 months decreased the frequency of hospitalizations for hyperammonemia, although it did not alter his neurologic status. This report demonstrates that persistent carnitine deficiency may be present in patients with ornithine transcarbamylase deficiency even when plasma ammonia is normal. Carnitine evaluation and supplementation may be important in the treatment of patients with this metabolic disorder.     

Overview of the Clinical Efficacy of Lamotrigine

Summary: Testing the efficacy of lamotrigine (LTG) in epileptic patients has been approached in several ways. The first pilot study examined the effect of a single dose of LTG in patients with frequent interictal spikes, and a reduction in spike frequency was observed. Subsequently, single doses reduced photosensitivity in appropriate patients. Single-blind administration of LTG for 1 week in addition to the patients' regular antiepileptic drugs (AEDs), in patients with refractory seizures, reduced seizures despite the short duration of therapy. This regimen was continued using a placebo-controlled crossover study with 1-week duration of treatment. Efficacy in partial and tonic-clonic seizures was subsequently confirmed in four double-blind crossover studies; a meta-analysis of these four studies showed a 30% reduction in partial seizures despite the intractable nature of the seizures in the patients included. Current studies aim at evaluating the drug as monotherapy and in different seizure types.     

Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo.

Killer lymphocytes play a major role in host defense against tumors and infectious diseases. Previously, we reported that delta-9-tetrahydrocannabinol (THC) and II-hydroxy-delta-9-tetrahydrocannabinol (II-hydroxy-THC) suppressed the cytolytic activity of cultured natural killer (NK) cells. Also, we showed that the drugs appeared to be affecting a stage in the killing process subsequent to the binding of the killer cell to the target cell. In the present report, we have extended these studies to an examination of the effect of cannabinoids on the activity of cytotoxic T lymphocytes (CTLs). The cytolytic activity of CTLs generated by cocultivation with either allospecific stimulators or TNP-modified-self stimulators were suppressed by both THC and II-hydroxy-THC treatment. Allospecific CTLs generated in vivo were also inhibited by an in vitro exposure to either THC or II-hydroxy-THC, and the sensitivity of these cells to drug effects appeared to be greater than the sensitivity of the in vitro generated CTLs. Suppression of cytolytic function by THC and II-hydroxy-THC was maximal after a 4-h drug treatment, suggesting that the drug effects were inducible and therefore required a finite period of time to develop maximally. As seen in previous studies involving NK cells, drug treatment of mature CTLs appears to have little effect on the binding capacity of these cells for the target. However, the maximal killing capacity of the cells and the frequency of CTLs were significantly reduced by drug treatment. In addition to suppressing the cytolytic activity of mature effector CTLs, we also show that drug treatment inhibits both the proliferation of lymphocytes responding to an allogeneic stimulus and the maturation of these lymphocytes to mature CTLs. Similarly, CTL activity developing in vivo could be inhibited by THC injection. These results suggest that CTLs are inhibited by cannabinoids by at least two mechanisms. First, the cytolytic activity of mature killers is suppressed at some point beyond the binding to the target cell. Second, the cannabinoids appear to suppress the normal development of these mature effector cells from less mature precursor cells.     

Nomogram for the prediction of unbound phenytoin concentrations in patients on a combined treatment of phenytoin and valproic acid

The interpretation of the total phenytoin (PT) concentration can be problematic if valproic acid (VPA) is given as a comedication, because VPA displaces PT from the protein binding sites and can increase the free fraction of PT. In order to estimate the free or unbound PT concentration (PTf) from the total PT concentration (PTt) and VPA concentration, a nomogram was constructed and evaluated. Data of 84 patients on combined therapy with PT and VPA were used in drawing up the regression equation (PTf = 0.0792.PTt + 0.000636.PTt.VPA) from which the nomogram was constructed. The predictions were checked using another 33 patients whose serum concentrations were determined in the morning and in addition several times during the day. The results show that using this method the PTf concentrations can be accurately estimated from the PTt and VPA concentrations.     

Gas chromatographic assay of methyltestosterone in tablets.

A simple gas chromatographic procedure has been developed for the determination of methyltestosterone in bulk powders and in tablets. Two new silyl ether derivatives of methyltestosterone have been prepared using dimethylethylsilylimidazole (DMESI) and dimethylisopropylsilylimidazole (DMiPSI). The method is accurate and selective for methyltestosterone within the concentration range 0.1-1.5 micrograms microliters-1.