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Biomedical subjects

J Tuomisto

Publications and source records attributed to J Tuomisto.

At least 145 records · Page 8Linked to original sources
PubMed1977

Nomifensine and its derivatives as possible tools for studying amine uptake.

An experimental antidepressive drug, nomifensine, was tested in simultaneous experiments as an inhibitor of the uptake of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) in rat brain synaptosomes. The drug was found to be a very potent inhibitor of NA (Ki 4.7 X 10(-9) M) and DA (Ki 2.6 X 10(-8) M) uptake, but relatively weak inhibitor of 5-HT uptake (Ki appr. 4 X 10(-6) M). According to kinetic studies on dopamine uptake, the inhibition was competitive. Time course studies indicated that the percentage inhibition did not increase with time. This finding suggests that inhibition of membrane uptake rather than inhibition of storage is the mechanism of action of this drug. 3 metabolites of nomifensine were also tested as inhibitors of NA and DA uptake. The addition of a 4-hydroxy group to the phenyl ring of nomifensine slightly decreased the potency, and addition of hydroxy and methoxy groups to the positions 3 and 4 in the phenyl ring, clearly decreased the potency. The structure of nomifensine is compared to that of chlorimipramine. It is suggested that the differences in selectivity as to dopamine and 5-HT uptake mechanisms might be due to 2 conformational differences: one of the phenyl rings is freely rotating in nomifensine but not in chlorimipramine, and the tertiary amine group is in a flexible side chain in chlorimipramine but rigidly tied in nomifensine.

Animals↗
PubMed1977

Sulfadiazine-trimethoprim combination in the treatment of urinary tract infections.

In a clinical double-blind study on 198 patients with a urinary tract infection, no differences were found between comparable groups treated with either sulfadiazine (SD) 1,000 MG/trimethoprim (TM) 320 mg or sulfamethoxazole (SM) 1,600 mg/trimethoprim 320 g daily for 2 weeks. The favorable results were obtained according to the bacteriological control in 85 and 79%, respectively. Also the incidence of side effects was the same (22 and 24%, resp.). The number of cases within which the treatment had to be discontinued did not differ percentually, either (6.6 and 8.4%, resp.). Based on the bacteriological sensitivity tests and the clinical trial, the authors conclude that TM can be combined with SD as well as with SM. Pharmacokinetic advantages, like a lower protein-binding and a lesser metabolism, may even make SD more preferable.

Acute Disease↗
PubMed1977

Evidence for dopaminergic control of thyrotrophin secretion in the rat.

The effects of two dopamine agonists (apomorphine and bromocriptine) and a dopamine antagonist (pimozide) on cold- or thyrotrophin releasing hormone (TRH)-induced TSH secretion were studied in normal male rats. Apomorphine given in various doses (0-5-10 mg/kg body wt) 10 min before exposure to cold significantly depressed TSH secretion. Large doses of bromocriptine (5-10 mg/kg body wt) given 1 h before exposure to cold, also blocked this response whereas a smaller dose (2-5 mg/kg body wt) given 30 min, 1, 3 or 6 h before cold exposure or repeated doses (0-1-2-5 mg/kg body wt) for 3 days did not modify cold-induced TSH secretion. Pimozide given in various doses (-25-2-5 mg/kg body wt) 1 h before exposure to cold did not alter the cold response, but 2-5 mg/kg reversed the inhibition caused by apomorphine or bromocriptine. None of these drugs affected TRH-induced TSH secretion. These results suggest that there are no dopaminergic receptors on the pituitary thyrotrophs, but that dopamine might be an inhibitory transmitter in the brain involved in the regulation of TSH secretion in the rat.

Animals↗
PubMed1976

Conformationally rigid amphetamine analogs as inhibitors of monoamine uptake by brain synaptosomes.

Four 3-phenyl-2-amino-trans-decalin isomers were synthesized in order to obtain derivatives of phenylethylamine with a rigid conformation between the phenyl ring and the amino function. The stereoisomers were tested as inhibitors of catecholamine uptake by rat brain synaptosomes, and their potency was compared with that of amphetamine. The most potent inhibitor of catecholamine uptake was the diaxial 2(a)-amino-3(a)-phenyl-trans-decalin, which was one-fourth to one-third as potent as (+/)-amphetamine. As a dopamine uptake inhibitor in the stiatum, this compound was competitive. The results differ from those obtained earlier with similar analogs with a norepinephrine moiety incorporated into the decalin structure, since a gauche derivative [2(a)-amino-3(e)-3,4-dihydroxyphenyl-3-trans-decalol] was then the most potent and over 20 times as potent as the diaxial anti derivative. It remains to be seen whether this indicates that the mode of binding of phenylethylamines is different from that of catecholamines.

2-Naphthylamine↗
PubMed1976

Effect of cold-exposure on serum thyrotrophin levels in man.

Serum TSH levels were measured after exposing male volunteers to cold, or successively to warmth and to cold, causing clear changes in body temperature. Very moderately heated Finnish sauna bath increased body temperature to about an average of 39 degrees C, and cooling in a relatively warm swimming pool (+25 to +28 degrees C, 30 min) decreased body temperature to below 35 degrees C after sauna, and to about 33 degrees C without sauna. In both cases a slight but significant initial increase of serum TSH was demonstrated. No changes in serum T3 or ETR were seen. The results suggest that a similar mechanism of initial TSH response may exist in humans as has previously been demonstrated in rats.

Adult↗
PubMed1975

Neurotransmitter control of thyrotropin secretion in the rat.

In rats adapted to a +30 degrees C temperature for one week, transfer to a temperature of +4 degrees C increased immunoassay-able serum TSH from 150-300 ng/ml to 800-2000 ng/ml in 30 min. Since this response, as well as the level of serum TSH without stimulation, were decreased by reserpine, phentolamine, phenoxybenzamine, disulfiram and diethyldithiocarbamate, noradrenaline may be involved in the stimulation of TSH secretion. TRH-induced TSH increased was not blocked by reserpine. 1-Dopa, a noradrenaline precursor, decreased the TSH response to cold; alpha-methyl-p-tyrosine increased the TSH level. Apomorphine decreased the level of serum TSH and inhibited the response to cold. The possibility of a dopaminergic inhibitory factor released from the hypothalamus is discussed. 5-HT has possibly a role in the regulation of TSH secretion, since its precursor 5-HTP decreased the response to cold. No indication was found that acetylcholine is involved.

Acetylcholine↗
PubMed1975

Absorption of erythromycin. A cross-over study in healthy volunteers.

The absorptions of 6 erythromycin preparations were compared in a cross-over study in healthy humans. In a single-dose study, 500 mg of each preparation was, after an overnight fast, given to 10 volunteers. The two enterosoluble preparations of erythromycin base studied were absorbed slowly, and the peak serum concentration (1.5-2 mg/l) was achieved only at 4 h. The absorption of the stearates was quick, but especially one of them was poorly absorbed, the serum concentration being always below 1 mg/l. Both of the two estolates gave highest apparent concentrations, and the maximum serum level (2-2.5 mg/l) was achieved at 2 h, but the concentration of active erythromycin remains unknown. In the second part of the study, two erythromycin stearates and one base preparation were given at 6-h interval in a cross-over fashion, each for 4 days. On the 4th day, blood samples were analyzed. The erythromycin base gave higher serum concentrations than did the two stearates, which were equivalent. It seems doubtful that the erythromycin stearate at the dose of 250 mg every 6th hour would give satisfactory serum levels of erythromycin which would be effective against most bacteria during the whole treatment.

Biopharmaceutics↗
PubMed1975

Uptake of histamine by rabbit hypothalamic slices.

The accumulation of [-14C] histamine into slices of rabbit hypothalamus was studied. All areas of hypothalamus took up histamine against a concentration gradient. The highest accumulation was into the infundibular area and the lowest into the mamillary body. The uptake did not correlate with the level of endogenous histamine. The uptake continued for at least two hours and a maximum tissue/medium ratio of about 5.6 was reached. The major part of radioactivity was chromatographically shown to be histamine. The uptake was temperature dependent and required sodium. It was not significantly inhibited by compound 48/80, but it could be inhibited with desipramine and 5-hydroxytryptamine. Therefore, the uptake of histamine shares many characteristics of the uptake of monoamines by brain slices, even if the rate of uptake appeared to be slower.

Animals↗