Biomedical subjects

G Tran

Publications and source records attributed to G Tran.

9 recordsLinked to original sources

PubMed1992

Effects of alcohol dependence on shock-induced fighting: action of muscimol and homotaurine.

We have applied the electroshock-induced fighting behavior to the study of experimental alcohol dependence. Adult Wistar rats were intoxicated chronically with ethanol (10 g/kg/24 h) for 13 days. Electroshock-induced fighting behavior was studied during chronic intoxication and withdrawal in comparison with normal rats receiving a water-carbohydrate solution isocaloric to ethanol. Rats were divided into groups receiving respectively muscimol (0.25 mg/kg), a GABAA agonist; homotaurine (140 mg/kg) a GABA mimetic; and physiological saline (10 ml/kg), intraperitoneally. During chronic intoxication, rats showed an increase in defensive-fighting behavior. Withdrawal accentuated the aggressive behavior and muscimol and homotaurine inhibited it. These results confirm the relevance of the electroshock-induced defensive fighting behavior test in chronic intoxication with alcohol, but to show the involvement of GABAergic transmission in the behavioral effects of alcohol withdrawal, additional experiments with other GABA mimetics and with GABA antagonists should be considered.

Aggression↗

PubMed1992

Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats.

Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H-GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour.

Acamprosate↗

PubMed1990

Circadian variations in vigilance states in the alcohol-dependent rat.

Waking and sleep states were studied in the alcohol-dependent rat after administration of ethanol (416 mg/kg/hr) by indwelling intragastric catheter (IGC) for 13 days. Electropolygraphic recordings performed for a total of 24 hr from the start of withdrawal were compared with those of control rats receiving water by IGC and showed 1) that rapid eye movement sleep was the most sensitive of the four vigilance states studied. A decrease was noted both for the total duration of recording and for the light period; 2) that nonactive wakefulness was the only vigilance state to show an inversion of percentages between the light and dark period; 3) that the light period was the best time for studying changes in vigilance states. Changes included increased percentages of active and nonactive wakefulness and decreased percentages of slow-wave and rapid eye movement sleep. This was due to a change in the number of episodes rather to a change in their mean duration. No significant change occurred during the dark period.

Alcohol Withdrawal Delirium↗

PubMed1990

Acamprosate appears to decrease alcohol intake in weaned alcoholics.

Five hundred and sixty-nine alcoholics were included in a double-blind placebo-controlled randomized multicenter study of the effects of Acamprosate (calcium acetylhomotaurinate (CA), 1.3 g/day) on indicators of alcoholic relapse after withdrawal. One hundred and eighty-one patients in the CA group versus 175 in the placebo group completed the three-month study. The major efficacy criterion was plasma gamma-glutamyl transpeptidase (GGT), as an indicator of recent alcohol ingestion. This analysis was completed by criteria concordance analysis on a number of indicators of alcohol intake. Patients in both groups were similar initially. After 3 months of treatment, the patients in the CA group had significantly lower GGT (1.4 +/- 1.56 versus 2.0 +/- 3.19 times normal, P = 0.016). All significant differences (P less than 0.05) or trends (0.10 greater than P greater than 0.05) were in favor of a superior effect of CA over placebo. The major side-effect of CA was diarrhea (present in 13% of CA patients versus 7% of placebo, P = 0.04). CA proved superior to placebo on the evolution of markers of alcohol ingestion at three months, in this large-scale multicenter study. It could be a new modality in the drug therapy of alcoholism, not involving an antabuse effect, an antidepressant action, or conditioning.

Acamprosate↗

PubMed1985

Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics.

After they had been weaned off alcohol in hospital 85 severe alcoholics (above 200 g alcohol/day) were included in a double-blind study of calcium bis acetyl homotaurine (Ca AOTA, 25 mg/kg/day), a new gamma-aminobutyric acid agonist, versus placebo. Patients were treated as outpatients during the 3-month study. The only other treatment that patients received was meprobamate, 800 to 1200 mg/day, in the first month. The criterion for success was abstinence at 3 months (with normal gamma-glutamyl transpeptidase being one of the criteria). Of the 70 patients who completed the study, 33 received Ca AOTA and 37 placebo. 20 patients on Ca AOTA did not relapse, compared with 12 on placebo (p less than 0.02 by X2 test). Side-effects were noted by 7 patients on Ca AOTA and 2 on placebo. The results suggest that Ca AOTA may be useful in helping severe alcoholics who have been weaned off alcohol not to relapse.

Acamprosate↗

PubMedDate not supplied

Dose-dependent suppression of the high alcohol intake of chronically intoxicated rats by Ca-acetyl homotaurinate.

The effect of taurine derivative, Ca-acetyl homotaurinate, on voluntary alcohol intake was investigated in ethanol-dependent and naive rats. A high 24 hr oral intake of a 10% ethyl alcohol solution (9-10 g/kg) was exhibited by rats following 15 days of intragastric infusions of ethanol (7-8 g/kg/day). In four groups, rats were IG injected by short pulses of isotonic saline or a daily dose of 200, 300 and 450 mg/kg respectively, distributed over six daily infusions during alternating 8 hr presentations of ethanol solution and water. Compared to their respective basal intakes during the first two days of injection, the rats demonstrated a dose-dependent 50 to 70% reduction in alcohol consumption with drug treatment. This suppression effect was specific to the ethanol solution and persisted during 4 days of post-treatment observation. In ethanol-naive rats similarly tested and drinking half the amount of alcohol drunk by their ethanol-dependent counterparts, only the highest dose of drug (450 mg/kg) significantly suppressed their alcohol intake. It is suggested that Ca-acetyl homotaurinate interacts with CNS mechanisms involved in the ethanol tolerance-dependence state, underlying an enhanced reinforcing property of ethanol oral intake. Opioid receptors could be the targets in this action.

Acamprosate↗

PubMedDate not supplied

Lack of effects of Ca-acetyl homotaurinate on chronic and acute toxicities of ethanol in rats.

In a previous study, it was shown that in rats Ca-acetyl homotaurinate suppresses or eliminates the high oral intake of ethanol induced by earlier chronic ethanol administration, and to a lesser degree the spontaneous ethanol intake of ethanol-naive rats. The present study examines the effect of the drug on the chronic and acute toxicity of ethanol as a possible mechanism in its alteration of the reinforcing properties of ethanol intake. In the first experiment, it was demonstrated that chronic administration of the drug (45 mg/kg per day) for 15 days, alone or combined with chronic intragastric administration of high doses of ethanol, did not significantly alter subsequent ethanol intake. In two other experiments, it was shown that the drug did not interfere with acute ethanol toxicity as tested by ethanol-induced hypothermia, motor impairment and taste aversion in ethanol-naive rats. It is concluded that the acute activity of Ca-AOTA on CNS mechanisms presumably involved in the state of tolerance-dependence, other than those concerned in ethanol-induced hypothermia, motor impairment and taste aversion, may explain its action on the reinforcing property of ethanol intake.

Acamprosate↗

PubMedDate not supplied

EEG effects of a single low dose of ethanol on afternoon sleep in the nonalcohol-dependent adult.

Three polygraphic recordings (PGR) of afternoon sleep (ANS) related to the duration of one sleep cycle, i.e., 90 min, were performed in 14 healthy adult volunteers (7 men and 7 women): two reference PGR, on two consecutive days (before ingestion of alcohol). Only the second being retained: reference PGR = P1; another recording, on day 3, 50 min after the start of single slow oral ingestion of the equivalent of 0.25 g 95% ethyl alcohol (ETOH) per kg body weight. Alcohol was ingested as 40 degrees whiskey, and the volume administered ranged from 34.5 to 66 ml (ETOH polygraphic recording = P2). Analysis of polygraphic traces was carried out according to the criteria of Rechtschaffen and Kales, and results were presented using the parameters adopted by Gross et al. (2). A single low dose of alcohol, leading to a low mean blood alcohol level (below 30 mg/100 ml, range 9 to 29 mg/100 ml), clearly perturbs sleep in the normal nonalcohol-dependent adult. In this context, ETOH does not appear to be a hypnotic since: a) the latencies to onset of sleep and the appearance of stages II, III, and IV of slow-wave sleep (SWS) are not shortened; b) the total duration of sleep, the percentage of delta sleep, and the duration (and percentage) of rapid eye movement sleep (REMS) are decreased; c) the number, duration, and percentages of intrasleep awakenings are increased, as are the number of stage changes. In addition, the study of afternoon sleep has shown itself to be a sensitive and reliable test for the analysis of the effects of a low dose of alcohol on nonalcohol-dependent subjects.

Adult↗

PubMedDate not supplied

Clinical pharmacology of gallium chloride after oral administration in lung cancer patients.

Pharmacokinetic parameters were determined in 18 lung cancer patients after a single administration of 800 mg/24 h of GaCl3: Cmax = 123 +/- 61 mu/l; Tmax = 5.2 +/- 5.5 h; AUCO-96h = 4690 +/- 3358 micrograms.l-1.h; AUCO - infinity = 6394 +/- 5352 micrograms.l-1.h; T 1/2 beta = 43 +/- 19 h. Serum Ga concentrations at the steady-state (Css) were then determined in these patients after a daily oral administration of 800 mg/24 h of GaCl3 for 15 days: Css = 274 +/- 167 micrograms/l. No correlation was found between Css and the previous pharmacokinetic parameters in each patient. Various doses of GaCl3 were administered daily to 45 patients to correlate Css and dosage. Serum Ga concentrations increased with dosage from 100 to 400 mg/24 h (p less than 0.05), but not with further dosages up to 1400 mg/24 h. The optimal daily dose of GaCl3 in lung cancer patients seems to be 400 mg/24 h. In 2 patients, Ga was assayed after death in tissues. Ga concentrations were more than 10 micrograms/g in metastases, 3.6 +/- 2.9 micrograms/g in the primary tumor and 2.3 +/- 0.9 micrograms/g in the kidney. Due to the lack of renal and hematological toxicities and the significant uptake of Ga by the tumor, GaCl3 can be used orally in conjunction with other cytotoxic agents. We intend to evaluate its efficacy according to a randomized study comparing chemotherapy versus chemotherapy plus 400 mg/24 h of GaCl3.

Administration, Oral↗