Clinical Efficacy of the 5-HT3 Antagonist Ondansetron in Alcohol Abuse and Dependence

Medications that act on the serotonergic system have been found to be of benefit in the treatment of alcohol-dependent individuals. In a randomized, placebo-controlled study, the efficacy of 6 weeks of ondansetron, a 5-HT₃ antagonist (0.25 mg bid or 2.0 mg bid), in the treatment of 71 nonseverely alcohol-dependent males was tested. The results showed reduction of drinking differences were steadily increasing toward the end of the treatment period approached significance at week 7 in the 0.25 mg group ( p = 0.06). Twice as many patients in this group showed >2 standard deviations decrease in drinking compared with the other groups. When patients drinking >10 drinks/drinking day at baseline ( n = 11) were excluded from the analysis, significant group differences were found at both treatment and follow-up, with the lower ondansetron dose producing the greatest reduction from baseline (i.e., 2.8 standard drinks; –35% compared with baseline and –21% compared with placebo; p < 0.02–0.001). Within this group, there was an almost 4-fold greater number of patients showing a clinically meaningful decrease in drinking. Lower baseline drinking and higher level of education were significant and strong predictors of drinking reduction during treatment. Ondansetron was very well tolerated; hence, further long-term studies with 5-HT₃ antagonists alone or in combination with other treatment components may offer promise for treatment of alcoholism.     

The relationship of health/food literacy and salt awareness to daily sodium and potassium intake among a workplace population in Switzerland

Background and aims

High sodium (Na) and low potassium (K) intake are associated with hypertension and CVD risk. This study explored the associations of health literacy (HL), food literacy (FL), and salt awareness with salt intake, K intake, and Na/K ratio in a workplace intervention trial in Switzerland.

Selective Inhibition of Alcohol Intake in Diverse Alcohol-Preferring Rat Strains by the 5-HT2A Antagonists Amperozide and FG 5974

The present studies sought to elucidate the role of 5-HT_2A receptor antagonists in suppressing alcohol intake by comparing the effects of amperozide and FG 5974 on alcohol, food, and water intake in strains of alcohol-preferring rats: P, Alko Alcohol (AA), and Fawn-Hooded (FH). Both amperozide and FG 5974 have 5-HT_2A receptor antagonist properties, but FG 5974 also shows presynaptic 5-HT_1A receptor agonist activity. After establishment of stable baselines for intake measures in a two-bottle continuous access paradigm, rats ( n = 10) were injected with 1 of 5 doses (0, 1.0, 2.5, 5.0, and 10.0 mg/kg, sc) of amperozide or FG 5974 at weekly intervals. Amperozide dose-dependently reduced alcohol intake, total fluid intake, and alcohol preference in all three strains under continuous access conditions, whereas FG 5974 was less effective. Food intake was also suppressed by amperozide at higher doses, whereas it was increased by FG 5974. Amperozide also dose-dependently reduced alcohol intake when it was available for only 1 hr/day, but FG 5974 tended to increase it. After oral administration, amperozide was also more effective than FG 5974 in reducing alcohol intake. Despite these differences in efficacy in suppressing alcohol intake, both compounds produced taste aversion to a novel saccharin solution. These complex findings suggest that biochemical properties other than 5-HT_2A receptor antagonism (e.g., 5-HT_1A receptor agonism) may be involved in the effects of amperozide and FG 5974 on alcohol intake and other consummatory behaviors.     

Resistance to subcutaneous and intramuscular insulin associated with deficiency of insulin-like growth factor (IGF) 2

A diabetic patient is described whose serum was deficient in IGF 2. The patient responded appropriately to intravenous insulin but was resistant to subcutaneous and intramuscular insulin. His serum degraded insulin in vitro. This degradation was inhibited by IGF 2 and to a lesser extent by IGF 1 and insulin. We propose that this patient inactivated insulin at the injection site because of an insulin protease in his tissues that would normally be inhibited by serum IGF 2.     

The significance of platelet-vessel wall prostaglandin equilibrium during exercise-induced stress

Alterations in platelet-generated thromboxane A₂ (TXA₂) and vessel wall-generated prostacyclin (PGI₂) have been assoclated with myocardial ischemia. To examine TXA₂ - PGI₂ equilibrium at rest and during exercise stress, we studied 13 normal subjects and 15 coronary artery disease patients. Plasma TXB₂ and 6-keto-PGF_1α were measured as stable metabolites of TXA₂ and PGI₂, respectively, by radioimmunoassay. In normal subjects, plasma TXB₂ levels increased 24% during exercise from 135 ± 30 to 168 ± 42 pg/ml (p = NS). Plasma 6-keto-PGF_1α levels increased 224% from 54 ± 17 to 175 ± 57 pg/ml (p < 0.05). In coronary artery disease patients, although resting plasma TXB₂ levels (mean 136 ± 43 pg/ml) were comparable to levels in normal subjects, a greater increase (82%) occurred during exercise (mean 248 ± 70 pg/ml; p < 0.02 compared to resting levels). Resting plasma 6-keto-PGF_1α levels (mean 94 ± 28 pg/ml) were also similar to normal subjects but increased only by 43% during exercise (mean 134 ± 53 pg/ml; p = NS compared to resting levels). These data suggest that: in normal subjects TXA₂ and PGI₂ increase during exercise, PGI₂ increasing more than TXA₂, and although coronary disease patients have resting TXA₂ and PGI₂ levels in the normal range, TXA₂ levels increase more than PGI₂ levels during exercise. These observations may have a bearing on the mechanism of exercise-induced angina pectoris in certain coronary artery disease patients.     

Rheumatoid vasculitis: Experience with 13 patients and review of the literature

Rheumatoid vasculitis is an uncommon but potentially catastrophic complication of RA. There are few current extensive experiences and no consensus regarding the clinical, laboratory, histologic features, and management or prognosis of rheumatoid vasculitis. We therefore reviewed selected observations in 13 patients followed over the past decade and compared them with patients reported and with results of a survey of North American Rheumatologists. Our patients were seven men and six women (age, 33 to 70 years) who had had active RA for 4 to 36 years. They exhibited sensory neuropathy, mononeuritis multiplex, Felty syndrome, cutaneous lesions, leg ulcers, gangrene, anemia, leukocytosis, eosinophilia, high titers of RF, hypocomplementemia, and CICs or cryoglobulinemia approximately as frequently as other reported patients with rheumatoid vasculitis, but they displayed constitutional symptoms, subcutaneous nodules, ischemic changes, and proteinuria rather less consistently than in other series. These observations were not necessarily as expected by survey respondents. We, as in other series and suggested by survey respondents, tended to select penicillamine or cytotoxic drugs (or plasmapheresis) for patients with mononeuritis, gangrene, or leg ulcers, and nonsteroidal antiinflammatory drugs, antimalarials, gold, or penicillamine for sensory neuropathy or digital lesions. Four patients died, two deteriorated, and seven were stable or improved, a finding that was also similar to the experiences of others. Rheumatoid vasculitis is an uncommon, potentially catastrophic syndrome with varying clinico-pathologic features that have different prognostic implications and should be managed individually.