Biomedical subjects
Publications and source records attributed to A Longo.
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The problem of the HLA association of Type 1 (insulin-dependent) diabetes was re-examined by testing Class II antigenic specificities detectable by radioimmunoassay. Established (DRw53, DQw1, DQw2, DQw3) as well as newly described (DC5, DCalpha3) specificities were typed. The data obtained suggest that the association with DR3 and DR4 is secondary to that with DQ specificities in linkage disequilibrium with DR3 and DR4.
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Ibopamine (SB-7505), the 3,4-diisobutyrylester of N-methyldopamine (epinine), was rapidly hydrolyzed to epinine by plasma esterases of rat as well as of other animal species and man. Ibopamine was rapidly and extensively metabolized after oral administration to rat. Plasma levels of free epinine peaked at 30-60 min from the administration; conjugated epinine was present in larger amount, with a maximum at 3 h. Both free and conjugated epinine were still detectable at 6 h, but not at 24 h. Epinine 4-O-glucuronide, 4-hydroxy-3-methoxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid appeared as main urinary metabolites; epinine 3-O-sulphate, epinine 3-O-methylether and its glucuronide, and trace amounts of epinine 4-O-sulphate were also detected.
Ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine (epinine), exerts, on oral administration, cardiovascular effects similar to those of intravenously infused dopamine. Plasma levels and urinary excretion of metabolites were investigated in dogs after oral administration of 4 mg/kg of ibopamine hydrochloride. Epinine, which was readily formed from ibopamine by esterases hydrolysis, was present in plasma in free and sulphate-conjugated form. The urinary metabolites after 6 h from the administration amounted to 62% of the dose, as a sum of 37% of epinine 3-O-sulphate, and 15 and 10% of 4-hydroxy-3-methoxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid, respectively, both in free and conjugated form. When the main metabolite, epinine 3-O-sulphate, was administered intravenously it appeared to be excreted in urine without being deconjugated to any detectable extent, while it appeared to be partially deconjugated on oral administration.
In order to describe kinetics after single administration and to test dose independence in the therapeutic dose range, ibopamine (SB-7505), the 3,4-diisobutyrylester of N-methyldopamine (epinine), was given orally to six healthy volunteers at multiple dose levels in a cross-over fashion. Doses employed were 50, 100 and 200 mg with a wash-out period of at least three days between doses. Plasma levels were studied after the 100 mg dose, and urinary recoveries of the major metabolites were measured after each dose. After oral intake of ibopamine, both conjugated and free epinine were detectable in plasma at the earliest sampling times (i.e. 5-10 min), with a hybrid absorption half-life of 0.25 h. Peak plasma concentration mean values of total and free epinine were 33 mumol/l and 35 nmol/l, respectively, and mean time to plasma peak concentration was 1.5 and 0.71 h, respectively. 24-h urinary recovery of conjugated epinine, homovanillic acid and dihydroxyphenylacetic acid accounted for about two thirds of the dose, without dose-dependent mechanisms affecting total elimination. Presystemic sulfate conjugation as a potentially saturable metabolic step at higher dose levels is discussed, although evidence was not found of its saturation in the studied dose range.
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A sample of 14 patients suffering from stable effort angina has been examined by means of exercise ECG test, in order to evaluate the efficacy, the onset of action and duration of effect of buccal nitroglycerin in the treatment of effort angina. The optimal dose of buccal NTG was predetermined for each patient through the analysis of heart rate changes (increase of at least 10 beats/min) and/or of blood pressure modifications (decrease of at least 10 mmHg). By applying a randomized double-blind design, the variations observed during exercise ECG tests after 20 minutes and 4 hours from the administration of buccal NTG (at the given dosage) or of placebo, have been evaluated. The following variables have been analyzed: heart rate, blood pressure, double product, time of onset of angina and/or of ST depression, amount of ST depression, duration of exercise test and maximum work-load. No significant changes have been observed for heart rate, blood pressure and double product both at the maximum effort and at the same level of effort as in the basal test. For each of the remaining variables a significant difference has been shown in favour of buccal NTG as compared to placebo, both after 20 min. and 4 hs. More in detail, the duration of the exercise test has been 6.14 +/- 2.77 mins on buccal NTG and 4.42 +/- 2.08 mins on placebo (+ 38%; p less than 0.05) after 20 mins and 6.40 +/- 3.19 on buccal NTG and 5.15 +/- 2.73 on placebo, after 4hs (+ 24%; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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Methionine-enkephalin, substance P, and homovanillic acid concentrations were measured in the CSF of subjects not affected by neurologic disorders (group 1), and in parkinsonian patients who had a slight or moderate (group 2) or severe (group 3) disability. Homovanillic acid and substance P concentrations in the CSF of groups 2 and 3 were respectively lower and higher than in group 1. On the contrary, an increase in CSF methionine-enkephalin content was found only in group 2. Our results confirm in humans the close relation between the dopaminergic and peptidergic transmissions in the nigrostriatal system that has been observed in experimental animals.
The authors appraise the weight modifications of residual splenic parenchyma after partial splenectomy (25%, 50%, 75%) in grown up rats. After the values of platelet rate in the blood had come back to standard, the residual spleens were removed and weighed. No difference of weight of the spleen was remarked in the control animals in which a mobilization of spleen and a resection of 500 mg. of hepatic parenchyma were performed; a difference of 0,15 g. (P greater than 0,05), 0,21 g. (P less than 0,05) and 0,18 g. (P less than 0,05) respectively was observed in rats with 25%, 50%, 75% splenectomy.
The authors report the modifications of platelet rate in the blood in a succession of total and partial splenectomies (25%, 50%, 75%) from the 40th day after operation till normalization. The values of platelet rate got back to standard in the 50th day in the animals subjected to 25% splenectomy, and in the 60th, 70th and 80th day from operation in the rats with 50%, 75% and 100% splenectomy. The data remarked suggest the period of thrombocytosis is in direct relation with the entity of plastrinosis, whereas the modalities of decrease are similar in all groups of animals.