[An evaluation of the therapeutic activity and tolerance of ST-679 in patients with osteoarthritis at different sites. A controlled double-blind study vs tolmetin]. / Valutazione dell'attività terapeutica e della tollerabilità di ST-679 in pazienti affetti da osteoartrite a diversa localizzazione. Studio doppio cieco controllato vs tolmetina.

A multicentered study was carried out, under double-blind conditions, on 160 elderly patients afflicted with differently localized symptomatic osteoarthritis, for the purpose of evaluating the therapeutical efficacy and tolerability of ST-679 (per-os at a dose of 1200 mg pro die in 80 patients) and to compare them with those of tolmetin (per os at a dose of 1200 mg pro die in 80 patients). It was demonstrated that ST-679 was significantly active on all of the clinical parameters of the illness already recorded after a month of treatment. ST-679 was always excellently tolerated as shown by the scarce incidence of adverse reactions. Results of laboratory tests, of tests for hidden blood in the feces and of a gastroduodenoscopy confirmed the excellent biological and gastric tolerability of ST-679. ST-679 demonstrated, moreover, a significantly better tolerability with respect to tolmetin.

Role of acetyl-L-carnitine in the treatment of cognitive deficit in chronic alcoholism.

Preliminary data are reported from a multicentred double-blind placebo-controlled study concerned with the effects of acetyl-L-carnitine (LAC) on some cognitive deficits of at least one month-abstinent alcoholics. Fifty-five patients, showing impaired performance in at least two out of six mnemonic, praxic and verbal tasks, were randomly assigned to either LAC 2 g/day or a placebo group. They were tested by means of a neuropsychological battery exploring the areas of memory, constructional praxia, deductive-logical functions and language. Testing time was on baseline (T0), after 45 (T45) and 90 (T90) days. On the Rey's 15 word memory test (long-term), the Wechsler memory scale (logical memory), and the Similarities WAIS subtest, the T90 difference between LAC and the placebo was significant in favour of the former treatment. On the copying drawing test (simple copy), the placebo group did not show any T0-T90 variation, while significant improvement in the LAC group was greater than in the placebo group. As LAC has proved to ameliorate the performance or to accelerate the recovery on tests representative of all cognitive areas explored, it is conceivable that the drug acts diffusely, either at the cholinergic transmission or at the neuronal metabolism level. It is concluded that acetyl-L-carnitine can be a useful and safe therapeutic agent in the subtle cognitive disturbances of chronic alcoholics.

Lethal effect of the serotonin-xylocaineR association in ganglion-blocked rats.

In rats anestetized with urethane and under ganglionic blockade by hexamethonium (20 mg/kg, i.v.), the i.v. injection of serotonin (60 mug/kg) determined apnea, ECG alterations and a brief hypotensive response which is similar to that as elicited when 5-HT is given to intact rats. During the hypertension which follows that initial response, apnea is still present along with more severe ECG changes. After that, blood pressure falls into a prolonged hypotension, which is invariably accompanied by death. Neither norepinephrine, nor respiratory analeptics (CoramineR, RemeflinF) were able to prevent the fatal outcome. Only artificial respiration was found to be useful in some instances. It was concluded that the association serotonin plus lidocaine becomes lethal when given to ganglion-blocked rate, and this toxic effect can be ascribed mainly to the respiratory depressor activity of the drugs.

[Sensitization of bradycardia during final hypotension induced by serotonin in rats: effect of lidocaine]. / Sensibilisation de la bradycardie pendant l'hypotension finale déclenchée par la sérotonine chez le rat: effet de la lidocaine

It was studied the sensibilizing effect of lidocaine (8.5 mg/kg, i.v.) on the ECG (heart rate, P-R interval, QRS complex and Q-T interval) of both intact and bilaterally vagotomised rats, in the nadir of the final hypotension determined by serotonine (60 mug/kg, i.v.). The results showed (1) a certain degree of selectivity of the vagi, and (2) the effects of serotonine either isolated or associated to lidocaine on P-R interval and heart rate were reinforced when intact animals were used. Although no significant alterations of Q-T were elicited by the drugs, lidocaine surprisingly enlarged the QRS complex in a more significant fashion for the intact than for the vagotomised animals.