Hopelessness and Excessive Drinking among Aboriginal Adolescents: The Mediating Roles of Depressive Symptoms and Drinking to Cope.

Canadian Aboriginal youth show high rates of excessive drinking, hopelessness, and depressive symptoms. We propose that Aboriginal adolescents with higher levels of hopelessness are more susceptible to depressive symptoms, which in turn predispose them to drinking to cope-which ultimately puts them at risk for excessive drinking. Adolescent drinkers (n = 551; 52% boys; mean age = 15.

Visual impairment and dysfunction in combat-injured servicemembers with traumatic brain injury.

Purpose: The purpose of this study was to determine the frequencies of visual impairment and dysfunction among combat-injured Polytrauma Rehabilitation Center (PRC) inpatient and Polytrauma Network Site (PNS) outpatient military personnel with traumatic brain injury (TBI).

Methods: A retrospective analysis of data from vision screenings of 68 PRC-inpatients with moderate to severe levels of TBI and 124 PNS-outpatients with mild TBI at the VA Palo Alto Health Care System was conducted.

Results: Eighty-four percent of PRC-inpatients and 90% of PNS-outpatients had TBIs associated with a blast event.

Experimental design: computer simulation for improving the precision of an experiment.

An interactive computer-assisted learning program, ExpDesign, that has been developed for simulating animal experiments, is introduced. The program guides students through the steps for designing animal experiments and estimating optimal sample sizes. Principles are introduced for controlling variation, establishing the experimental unit, selecting randomised block and factorial experimental designs, and applying the appropriate statistical analysis.

Sample Power and ExpDesign: tools for improving design of animal experiments.

Proper experimental design, involving the correct number of animals, should be a basic skill for any scientist working with animals. The authors describe a university-developed and freely available tutorial program and an interactive computer-assisted learning program, both of which guide students through the steps necessary for designing animal experiments and estimating optimal sample sizes.

Cardiac effects of benzodiazepine receptor agonists and antagonists in the isolated rat heart: a comparative study.

Effects of PK 11195 and flumazenil on cardiac responses to diazepam, clonazepam and zolpidem were compared. Coronary flow rate was increased at relatively low doses of diazepam and decreased at higher doses. Clonazepam induced a dose-dependent increase, and zolpidem a decrease of coronary flow rate.

L-Methadone and D,L-methadone in methadone maintenance treatment: a comparison of therapeutic effectiveness and plasma concentrations.

The clinical effectiveness of l-methadone maintenance treatment (LMMT) carried out using d,l-methadone or l-methadone have been compared with ambulatory heroin-dependent subjects. A total of 40 heroin-dependent subjects, previously maintained on l-methadone in Frankfurt am Main, were divided into two groups under randomised double-blind conditions and received either an equivalent dose of l-methadone as d,l-methadone or remained on the previous l-methadone treatment. Requests for a change in the dose of d,l-methadone and l-methadone were recorded, urine samples for determination of illicit drug use were collected and the individual level of opiate craving was determined over a 22-day observation period.

Modification of cardiac actions of RO 05-4864 by PK 11195 and flumazenil in the perfused rat heart.

The benzodiazepine analogue Ro 05-4864 [chlorodiazepam] (2.10[-5] to 4.10[-4] M) induced a concentration-dependent increase of coronary flow rate (Emax 82.

Flunarizine but not theophylline modulates inotropic responses of the isolated rat heart to diazepam.

Diazepam (2 x 10(-5)-6 x 10(-4) M) induced a concentration-dependent positive inotropic effect on the perfused rat heart which was preceded by a transient concentration-dependent negative inotropic response. The influence of the Ca(2+)-entry blocking drug, flunarizine, and the adenosine receptor blocking drug, theophylline on these inotropic responses was studied. Flunarizine in concentrations of 10(-9)-10(-6) M antagonized the positive inotropic response to diazepam significantly; the negative inotropic response was reduced as well.

PK 11195 antagonizes the positive inotropic response of the isolated rat heart to diazepam but not the negative inotropic response.

The influence of the ligand PK 11195 (1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl)-3-isoquinolinecarboxamide), antagonist of the peripheral-type benzodiazepine receptor, on the inotropic response of the perfused rat heart to diazepam (7-chloro-5-phenyl-methyl- 1,3-dihydro-2H-1,4-benzodiazepin-2-one) was studied. Diazepam induced a positive inotropic response which was preceded by a transient negative inotropic response. Concentrations of 10(-7) M PK 11195 were ineffective, whereas concentrations of 10(-6) and 10(-5) M PK 11195 reduced the positive inotropic response significantly.

Pharmacokinetics of methadone and its primary metabolite in 20 opiate addicts.

In a closed metabolic ward the pharmacokinetics of methadone and its primary metabolite (EDDP) were studied in 20 long-term opiate addicts. After administration of the daily oral dose of methadone HCl (mean 60 mg, range 10-225 mg) blood samples were taken and analysed, using a newly developed high-performance liquid chromatography (HPLC) method. The steady-state plasma concentrations of the 20 subjects varied from 65-630 ng x ml(-1) and from 5 to 55 ng x ml(-1), whereas the peak concentrations were 124-1255 ng x ml(-1) and 10-301 ng x ml(-1) for methadone and the AUC(0-24 h) for EDDP varied from 5.

Ivermectin detection in serum of onchocerciasis patients: relationship to adverse reactions.

Ivermectin treatment of onchocerciasis patients can be accompanied by adverse reactions. Not much is known concerning the pathogenesis of these reactions. Previous studies have demonstrated that the occurrence and extent of adverse reactions are related to infection intensity.

Actions of benzodiazepines on the inotropy of the perfused rat heart.

The inotropic responses of four benzodiazepines (diazepam, midazolam and the more recently developed adinazolam and alprazolam) have been studied in a Langendorff heart preparation of the rat. Added to the perfusate in increasing concentrations (2 x 10(-5) to 6 x 10(-4) M), diazepam induced a concentration-dependent biphasic effect on the contractile force (n = 12), and, in low concentrations (2 x 10(-5) to 1 x 10(-4) M), a significant enhancement which diminished after concentrations higher than 1 x 10(-4) M were applied. The increase in contractile force was preceded by a transient short-lasting concentration-dependent inhibition.

The effects of pentobarbital and benzodiazepines on GABA-responses in the periphery and spinal cord in vitro.

Pentobarbital and benzodiazepines were compared in their interaction with the gamma-aminobutyric acid (GABA) antagonists picrotoxin and bicuculline on GABAA receptor-mediated events. On excised vagal nerves and dorsal roots pentobarbital, in contrast to the benzodiazepines diazepam, lorazepam and flurazepam, was able to enhance GABA-induced depolarizations recorded in the presence of picrotoxin or bicuculline. On hemicord preparations picrotoxin simultaneously depressed the electrically evoked dorsal root-dorsal root potential and enhanced the dorsal root-ventral root potential.

Changes induced by diazepam in the synaptic vesicle size of rat phrenic nerve terminals.

The effect of diazepam (Valium), administered by i.p. injection on the cross-sectional area of synaptic vesicle profiles of the endplate-rich area of the rate diaphragm was studied by electron microscopy at 15-180 min after treatment.

Presynaptic, facilitatory effects of the corticosteroid dexamethasone in rat diaphragm: modulation by beta-bungarotoxin.

Low concentrations of dexamethasone (up to 200 nM) increase the accumulation of choline (Ch) and its incorporation into acetylcholine (ACh) in the endplate rich area (EPA) of stimulated and unstimulated diaphragms in the presence of 10 microM Ch. Tissue ACh is not significantly altered, even after 140 min incubation. The specific radioactivity of the ACh in the EPA is thus increased by dexamethasone (Dex).

Ion channel block in rat diaphragm by the venom of the digger wasp Philanthus triangulum.

In the rat phrenic nerve-diaphragm preparation the twitch tension and tetanic contractions, already reduced by d-tubocurarine, succinylchloride or neostigmine, are further reduced by the venom of the digger wasp Philanthus triangulum F. The venom reduces the temperature- and voltage-sensitivity of the acetylcholine-receptor-activated ion channels, at the motor end-plate, and shortens the decay time of the miniature end-plate currents, analogous to a block described for the purified toxin, delta-PTX, on insect glutamate-activated channels. Preliminary results show that delta-PTX has an effect similar to that of the total venom on the decay phase of miniature end-plate currents.

Effects of corticosteroids on the myoneural junction. A morphometric and electrophysiological study.

The mean size of the synaptic vesicles in the nerve endings of the isolated rat diaphragm was significantly increased after incubation with the glucocorticoids prednisolone (10(-5) mol/l) and dexamethasone (2 X 10(-7) mol/l). The shape of the vesicles was also changed, i.e.

Effects of corticosteroids on neuromuscular blocking actions of d-tubocurarine.

Dexamethasone (50 microgram/kg) significantly increased the LD50 of d-tubocurarine (d-TC) when administered i.p. simultaneously with d-TC.

The effect of prednisolone on neuromuscular transmission in the rat diaphragm.

Prednisolone, in concentrations of 0.004--0.032 mmol/l, increased the amplitude of the miniature end-plate potentials (MEPPs).