Publications

In order to estimate within-subjects variability in 24-hour energy expenditure at a fixed physical activity programme with a physical activity index of 1.30, this quantity was measured in four apparently healthy subjects once a month over 10 months. The coefficient of variation of the measurements was found to be between 2.7 and 4 per cent and in agreement with previously published data.

As measured by electromagnetic blood flow transducers, direct infusion of epinephrine, norepinephrine, and dopamine into the portal vein (PV) produced a 40-50% decrease in hepatic arterial (HA) blood flow; isoproterenol increased HA flow by about 69%. No changes in PV flow or pressure were observed. Direct HA infusion of the vasoconstrictors decreased HA flow by amounts comparable to those occurring after PV infusion. However, HA infusion of isoproterenol increased HA flow only 15% suggesting a difference in beta-receptor population in the two vessels. When infused directly into the superior mesenteric artery (SMA), epinephrine and norepinephrine reduced SMA flow by about 45% and PV flow by 20-25%; HA flow increased 6-8%. Infusion of isoproterenol and dopamine into SMA increased SMA flow by 115% and 206% and PV flow by 60% and 70%, respectively, whereas HA flow decreased by 25% and 50%. Portal vein pressure increased less than 3 mmHg. Alpha- and beta-receptor blockade of the liver did not change significantly the alterations in hepatic arterial blood flow that were secondary to changes in portal venous blood flow. It is likely that regulation of hepatic arterial flow resides in mechanisms located within the liver sinusoids.

RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level.

The reaction of the analgesic amidopyrine (100 mg) with nitrite extracted from cured meats and from spinach in varying degrees of spoilage was studied. Unde physiological conditions the carcinogenic dimethylnitrosamine was formed at milligram levels at nitrite concentrations as low as 4 mg (in 175 ml extracted from 100 g boiled ham). The rate of decrease in concentration in the human stomach after ingestion of amidopyrine and of nitrite contained in boiled ham or in a broth from boiled ham was also measured.

Phenothiazine-induced bone marrow depression (BMD) was evaluated in three separate but complementary data bases: (1) Among 1,048 patients admitted to psychiatric hospitals, there was no evidence of subclinical depression of the white blood cell (WBC) count attributable to phenothiazines used before admission. (2) Among 18,587 medical inpatients, there were 34 patients admitted for BMD in the absence of neoplasia or prior cytotoxic drug therapy; one of the latter reported using chlorpromazine hydrochloride, but it is doubtful whether this drug was the cause of the BMD. (3) Among 24,795 medical, surgical, and gynecological patients surveyed over a ten-month period in 1972, there were four who were admitted for BMD; one of the latter had a reversible leukopenia attributed to trifluoperazine hydrochloride.

About 30% of boar seminal plasma nitrogen is maximally precipitated at room temperature by 6 to 10 mM zinc in citrate solution at pH 8. A rise in the total nitrogen precipitated by 1 to 6 mM zinc is accompanied by a fall in the haemagglutinin titre of the supernatant fluid. At 6 mM zinc addition, 95% of the haemagglutinin is precipitated, but much of this is recoverable by re-solution of the zinc precipitate. Protein profile studies by gel-filtration chromatography of the zinc precipitate solution reveals a mixture of proteins, some of which are not by themselves zinc-precipitable.