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Biomedical subjects

P Ferrari

Publications and source records attributed to P Ferrari.

At least 361 records · Page 20Linked to original sources

[Sequential angio-urography (SAU) with photographic image subtraction].

Urography was performed in 250 patients: the technique of bolus injection of a large quantity of contrast medium was used in every case. By means of rapid seriography the early vascular phase was shown and reproduced, when necessary, with image subtraction. The abdominal aorta and the renal arteries were demonstrated in 97.6% of cases. Altogether, in 34.4% of cases the existence of pathological conditions non demonstrable by conventional urography was ascertained; in 12.4% of cases extrarenal pathology was diagnosed. This technique is suggested to be used sistematically, as an alternative to DSA, where digital equipments are not available.

Adolescent↗

Synthesis and in vitro biological evaluation of N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosamino)-L-alanine (L-alanosine AICO ribonucleoside).

L-Alanosine [3-(hydroxynitrosoamino)-L-alanine] is an antitumor antibiotic that at the present is undergoing phase II clinical trials. Its mode of action as well as its metabolism has been extensively studied, and the metabolite N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosoamino)-L-alanine ribonucleotide (L-alanosine AICOR) proved to be an extremely potent inhibitor of de novo purine biosynthesis and is thus primarily responsible for the antitumor activity of the drug. The synthesis of the corresponding ribonucleoside, i.e., N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosamino)-L-alanine ribonucleoside (L-alanosine AICO ribonucleoside), was accomplished by condensation of a suitably protected derivative of L-alanosine with N-succinimidyl-5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1H-im idazole-4-carboxylate followed by the removal of the protective groups. The biological activity of L-alanosine AICO ribonucleoside was tested in vitro on whole tumor cells and on the isolated enzyme adenylosuccinate synthetase and in vivo on murine experimental leukemia. The compound was found to be inactive in these tests.

Antibiotics, Antineoplastic↗

Genetic hypertension and the kidney.

The relationship between the kidney and genetic hypertension has been assessed in light of the changes seen in some kidney and cell functions during the phases preceding and accompanying the development of "genetic" types of hypertension in rats and humans. Comparison of the kidney function of normotensive subjects likely to develop hypertension with that of matched controls resistant to hypertension showed, in the former, a higher glomerular filtration rate (GFR), greater tubular reabsorption, larger 24-h urinary output, larger fraction of cardiac output to the kidney, and lower plasma renin activity. After the transplantation of a kidney from a subject in the hypertension-prone group, recipients had higher blood pressure and required more antihypertensive therapy than recipients of kidneys from the hypertension-resistant group. In humans this finding is not as clear as in rats. During the development of hypertension most of these differences in kidney function in the two groups of subjects tend to disappear. The changes in cell function, measured particularly in rats, were consistent with the organ function changes. Cell volume and sodium content were lower, while the transport rate across the cell membrane was faster in proximal tubular cells of rats with genetic hypertension than in the appropriate controls. This is in keeping with the concept of a primary increase in proximal tubular reabsorption leading, on the one hand, to an increase in GFR and renal blood flow and a decrease in renin and, on the other, to an increase in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Follow-up study of 482 cases with convulsive disorders in the first year of life.

A total of 482 patients who had had one or more seizures in the first year of life were followed for at least five years (most for more than 10 years). The patients were divided into four groups: febrile convulsions, infantile spasms, status epilepticus and 'other'. Of those with febrile convulsions, 62 per cent developed normally, compared with 14 per cent in the group with infantile spasms, 15 per cent with status epilepticus, and 24 per cent in the 'other' group. Findings on recurrent seizures, epilepsy and mental retardation and/or neurological abnormalities are also reported. Epilepsy developed equally frequently among those with partial and with generalised seizures, but the former more frequently became mentally retarded. The effects of severity of seizures and other factors are discussed. In general, this research confirmed the grave prognosis after seizures during the first year of life, and not only for West syndrome and status epilepticus. The outcome was more favourable when the seizures were cryptogenic or febrile, isolated, with onset in the second six months, generalised, and when the EEG was normal between seizures.

Age Factors↗

Multiple sclerosis in the Republic of San Marino.

Previous studies on the prevalence of multiple sclerosis in Italy have grossly underestimated the prevalence of the disease. The prevalence in the Republic of San Marino (near Rimini), in Sicily, and no doubt in the rest of Italy, is of the same order of magnitude as in Europe--that is, 40-60/100 000. The contrast of this with the very low prevalence in Malta (only 60 miles (96 km) away from Sicily) of 4/100 000 should provide a clue to the genetic and environmental factors responsible for multiple sclerosis.

Adult↗

Metabolic pathways of the contragestational agent, 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (DL 111-IT), in the rat.

The metabolic pathways of the non-hormonal anti-fertility agent 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (DL 111-IT) were studied in rats given the 14C-labelled compound intramuscularly. The diaryltriazole, once absorbed, was metabolized rapidly by three phase I reactions: (a) hydroxylation at the C-4 of the methoxyphenyl ring, (b) hydroxylation at the alpha-C of the ethyl chain, and (c) demethylation of the methoxyl function. Seven free metabolites and three conjugates have been isolated and characterized by u.v., i.r., n.m.r. and mass spectroscopy. The products of the first step of metabolism of the diaryltriazole were tested for their pregnancy-terminating activity in the rat. They were only 5-9% as effective as the parent compound, indicating that the unchanged drug is the active molecule.

Abortifacient Agents↗

Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. V. Aromatic constituents.

Oxidative and hydrolytic degradation reactions were carried out on teicoplanin in order to characterize the aromatic portion of the molecule and relate it to the other members of the class of glycopeptide antibiotics. Seven aromatic rings, obtained as triphenyl ether, diphenyl ether, and diphenyl moieties after oxidation nd hydrolysis of teicoplanin, were identified. They are present in teicoplanin as aromatic amino acids and constitute the peptidic part of the molecule. The diphenyl ether and diphenyl moieties, which were isolated both as esters after oxidation and as alpha-amino acids after acid hydrolysis clearly indicate the nature of the corresponding amino acids in teicoplanin. The triphenyl ether moiety, which was isolated only as ester, allows the hypothesis that the corresponding amino acids are the same as those of the other glycopeptide antibiotics.

Actinomycetales↗

Histaminergic H1 and H2 receptors do not mediate cortisol release in response to naloxone in normal men.

In order to evaluate the role of histamine as a possible mediator of the ACTH-cortisol response to naloxone, a specific opioid receptor antagonist, 12 normal men were treated with naloxone before and after the administration of dexchlorpheniramine and cimetidine, respectively H1 and H2 histamine receptor antagonists. Cortisol levels in the plasma were measured before and after drug injections. Naloxone significantly stimulated the secretion of cortisol in all subjects; the administration of dexclorpheniramine or cimetidine failed to modify this response. These data confirm the stimulatory effect of naloxone on cortisol secretion, but do not support the hypothesis that a histaminergic pathway mediates this response.

Adrenocorticotropic Hormone↗

Structure identification of rifampicin N-oxide.

1H- and 13C-N.M.R. spectra, in addition to previous physicochemical data, confirm the structure of rifampicin N-oxide and indicate that the oxygen atom is bonded to the piperazine N--CH3 group.

Chemical Phenomena↗

[Early infantile autism and its biochemistry].

In the first part of this paper the different orientations of biochemical research in early infantile autism are recalled. The most significant results of these studies concerning the dopaminergic, noradrenergic and indolaminergic (serotonin, efflux, uptake) systems as well as the various enzymatic complexes are also reviewed. In the second part, the methodologic problems which arise in biochemical research in the field of autism are addressed.

Autistic Disorder↗

Medroxyprogesterone acetate (MAP) plasma levels after multiple high-dose administration in advanced cancer patients.

Medroxyprogesterone acetate plasma levels were measured in advanced cancer patients after multiple PO or IM administration (500, 1000, 2000, 3000, 4000, and 5000 mg/day PO and 500, 1000, 2000 mg/day IM for 30 days). After PO administration, the plasma concentration rises quickly and plateau level is reached in 4-10 days. Discontinuation of the treatment produces a fast decay (t1/2 = 62.4 h) of the drug levels. When medroxyprogesterone acetate is given IM plasma levels, steadily increase and after drug discontinuation no noticeable decay is observed for at least 6 months; plateau plasma levels are about three times higher than after the corresponding PO treatment. Extremely high interpatient variation in bioavailability is present with both administration routes. These data may well rationalize the results of previous clinical trials and will help in planning treatment schedules.

Administration, Oral↗

Effects of antihypertensive drugs on sexual behaviour of male rats.

Equiactive antihypertensive doses of clonidine, alpha-methyldopa, hydralazine, propranolol and of a novel compound 355-1057 were tested in an experimental model in which sexual activity was stimulated pharmacologically by lisuride. It was found that those antihypertensive drugs known to cause disturbances in sexual function in men, i.e., clonidine, alpha-methyldopa, hydralazine and propranolol, inhibited lisuride-induced mounting behaviour in male rats, as measured by a decrease in the percentage of animals mounting or in the number of mounts per active animal. The novel antihypertensive compound 355-1057, that seemed in preliminary clinical trials to be devoid of sexual side-effects in men, had no significant effect on the mounting behaviour. It seems, therefore, that the present experimental model could be predictive for antihypertensive drug-induced sexual side-effects in man.

Animals↗

Renal dysfunction as a possible cause of essential hypertension in predisposed subjects.

In 65 young normotensive subjects with two hypertensive parents (HP), and in 55 matched subjects with two normotensive parents (NP), the following factors were measured: renal plasma flow (RPF), glomerular filtration rate (GFR) both as Inutest and creatinine clearances; 24-hr urinary output; plasma renin activity (PRA); Na and K in plasma and in 24-hr urine and 24-hr urinary excretion of aldosterone. In 30 HP and in 34 NP, the cardiac output and plasma concentrations of noradrenaline, adrenaline, and dopamine were also measured in the supine position and after 10 min of standing. The HP have greater RPF (P less than 0.01), faster GFR (P less than 0.02), greater 24-hr urinary output (P less than 0.05), and lower PRA (P less than 0.01) than the NP. All the other factors were similar in the two groups of patients. It is proposed that the differences in renal function in the HP and the NP may be due to an abnormality in tubular handling of ions and water in the HP, which may be responsible for the increase in blood pressure in a proportion of patients with essential hypertension.

Adolescent↗

Disposition and metabolism of a new steroidal anti-inflammatory agent, deflazacort, in cynomolgus monkeys.

The kinetics and metabolic fate of 2'-14C-deflazacort, a new steroidal antiinflammatory agent, were studied in the cynomolgus monkey after both p.o. and i.v. administration (5 mg/kg). There is no unchanged deflazacort in the plasma or urine after either p.o. or i.v. treatment. As judged from the plasma AUC and urinary elimination values, the oral availability of both total 14C and metabolites seems to be lowered because of a route-dependent first-pass. Both radioactivity and the main metabolite (21-desacetyl deflazacort) are eliminated from the plasma with half-lives of 2--3-5 h. The i.v. administered 14C is eliminated mainly in the urine (52--55% of dose), but biliary excretion is also quantitatively important. Six metabolites were isolated from urine and identified by physico-chemical analysis. Among them desacetylated deflazacort and its 6 beta-hydroxy derivative were shown to be the major radioactive products in plasma and urine, respectively. Minor metabolites were: 21-desacetyl, 6 alpha-hydroxy deflazacort; 21-desacetyl, 5 alpha, 1-eno, deflazacort; 21-desacetyl, 20 beta hydroxy deflazacort; and 21-desacetyl, 11-keto deflazacort.

Animals↗

Expression at the haemopoietic stem cell level of the genetically determined erythrocyte membrane defects in the Milan hypertensive rat strain (MHS).

Both humans and rats with essential or genetic arterial hypertension show many alterations of erythrocyte membrane ion transport. The Milan hypertensive rat strain (MHS) has smaller red cells and faster Na+/K+ cotransport across erythrocyte membrane when compared with the control strain (MNS). In order to distinguish if these alterations are due to some inherited cell membrane characteristics or are secondary to some extrinsic factor responsible for hypertension, we have transplanted bone marrow (BM) cells from MHS or MNS rats to two groups of F1 hybrids, lethally irradiated (850 R). Three months after BM transplantation the F1 recipients were killed and their erythrocytes studied. The differences between erythrocytes of F1 MHS BM recipients and F1 MNS BM recipients follow the same pattern described for the donor parental strains. These results indicate that the MHS red cell abnormalities are present in the haemopoietic stem cell and therefore the MHS erythrocyte defects are not due to some extrinsic factors.

Animals↗