Biomedical subjects

G Tran

Publications and source records attributed to G Tran.

5 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↗

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↗