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Biomedical subjects

P Ferrari

Publications and source records attributed to P Ferrari.

At least 343 records · Page 19Linked to original sources
PubMed1987

Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. VIII. Opening of the polypeptide chain of teicoplanin aglycone under hydrolytic conditions.

Hydrolysis of teicoplanin (a complex of five closely related factors plus one, more polar component) under selected conditions (acids in a biphasic hydroalcoholic medium) gives the single aglycone with good yields. When the reaction is carried out in homogeneous hydroalcoholic phase the removal of the sugars yields two new compounds. On the basis of fast atom bombardment mass spectra (FAB-MS), acid-base titration, IR, UV and 1H NMR analyses it has been demonstrated that these compounds are two diastereoisomers; they differ from the teicoplanin aglycone in having additional carboxyl and amino groups derived from the hydrolysis of an amide bond. Although the molecular shape of the new aglycones is greatly modified, they still maintain some antibacterial activity which might be correlated with residual binding ability towards the terminal D-alanyl-D-alanine residue of the cell-wall mucopeptides.

Actinomycetales↗
PubMed1987

[CT study of the carpal tunnel. Normal anatomy].

The standard technique for CT investigation of the carpal tunnel and its normal anatomy were studied. Ten healthy asymptomatic volunteers, age 25-45, underwent wrist CT. The hand is placed in prone position with the third metacarpus in line with the radius. Digital radiograph and four axial CT scans are performed respectively: at the distal end of the radius, at the scaphoid tubercle level, at the hamate hook level and at the carpal-metacarpal joint. Standard carpal tunnel diameters are thus available with good reliability and repeatability when correct technique is adopted. The results permit a morphological description of the osseous walls, transverse ligament, flexor tendons with synovial sheets and median nerve. Gujon's canal and its content can also be investigated.

Adult↗
PubMed1986

Triplet pregnancy after low-dose pulsatile gonadotropin-releasing hormone in polycystic ovarian disease.

In a patient with polycystic ovarian disease, low-dose intravenous pulsatile gonadotropin-releasing hormone (5 mcg every hour) and no exogenous human chorionic gonadotropin induced multiple follicular development and elevated estrogen levels and resulted in a triplet pregnancy. Patients with polycystic ovarian disease may have a higher risk of complications and should be monitored more closely during ovulation induction with pulsatile gonadotropin-releasing hormone.

Adult↗
PubMed1986

Renal mechanisms and calcium in the pathogenesis of a type of genetic hypertension.

Results concerning kidney and red blood cell (RBC) function of Milan hypertensive rats (MHS), and of their age- and body weight-matched normotensive controls (MNS), are summarized. Our data suggest a biochemical and physiological link between RBC abnormalities and the renal mechanisms causing hypertension in MHS, and therefore the possibility of using the former as a tool for studying the genetic biochemical mechanisms of hypertension. In particular, the following results are discussed: a positive correlation between blood pressure and RBC Na+-K+ cotransport found in the F2 generation, obtained by crossing F1 (MHS X MNS) hybrids; bone marrow transplantation from MHS and MNS into F1 hybrids, causing a parallel change in recipient RBC characteristics; and similarities between erythrocytes and renal tubular cells in Na+ content, cell volume, and Na+ transport. Ca2+ ATPase or Ca2+ pump at Vmax are lower in MHS renal tubular cells and MHS erythrocytes than in MNS cells. Moreover, isolated kidneys of MHS and MNS, perfused in vitro with media at different Ca2+ concentrations, showed that the function of MNS kidney remained stable over a range of Ca2+ from 0.75 to 1.25 mM, while the function of MS kidney deteriorated at a Ca2+ concentration of 1.25 mM.

Adult↗
PubMed1986

Genetic and experimental hypertension in the animal model-similarities and dissimilarities to the development of human hypertension.

In this article, we present the results we have obtained from experimental and genetic models of human essential hypertension, in order to investigate those findings relevant to understanding the time course and the mechanisms underlying the human disease. With experiments on the renal artery constriction in the conscious dog, we have shown that a kidney lesion can produce a form of hypertension not different, in the established phase, from the essential one and that the onset of this form follows a phasic pattern during which the initial stages are crucial for understanding the mechanisms leading to hypertension. We also consider a rat model (MHS) that spontaneously develops a form of hypertension very similar to the human disease. In this model, we have demonstrated by a kidney cross-transplantation experiment and functional studies that the kidney is responsible for the rise in blood pressure and that the organ dysfunction is probably due to a primary abnormality in ion handling of the cell membrane. This cellular alteration, detected both in MHS erythrocytes and in their kidney proximal tubular cells, should be the cause for the higher rate of kidney Na+ reabsorption observed in the MHS. Comparing this animal model with, at least, a subgroup of humans prone to develop hypertension or already hypertensive, it is possible to detect a series of similarities in the kidney function, hormonal pattern, and cellular function of the two species that allows us to argue that the MHS is a suitable model from which to draw conclusions relevant to the pathogenesis of essential hypertension in some humans.

Animals↗
PubMed1986

Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. VII. Preparation and NMR characteristics of the aglycone of teicoplanin.

Several hydrolytic reactions that transform teicoplanin or its pseudo-aglycones into the aglycone with good yields are described. The most interesting approach is hydrolytic removal of the sugars in benzyl alcohol with the formation of the aglycone benzyl ester which is then submitted to hydrogenolysis. A detailed description of the 1H and 13C NMR spectra of the teicoplanin aglycone hydrochloride is presented. All the signals were attributed to the hydrogen and carbon atoms using homo and heteronuclear COSY. The relevant interactions through space between the hydrogen atoms were obtained by NOE. The structural aspects are discussed in terms of the well-known mechanism of action of the glycopeptide antibiotics.

Anti-Bacterial Agents↗
PubMed1986

Cell membrane abnormalities and genetic hypertension.

Evidence indicates that an alteration in kidney function has a causal role in the pathogenesis of hypertension in the Milan hypertensive strain (MHS) rat. At the prehypertensive stage, these animals have increased glomerular filtration rate and 24-hour urinary output, whereas plasma renin activity and urinary kallikrein are lower. After transplantation, the MHS kidney increases the blood pressure of a normotensive recipient. Micropuncture experiments, where single nephron filtration rate, tubuloglomerular feedback, proximal tubular reabsorption, micro-pressures in tubuli, and interstitium and interstitial oncotic pressure were measured, suggest that the intrinsic ability of MHS proximal tubular epithelium to reabsorb solute and water is greater in prehypertensive MHS rats than in Milan normotensive strain (MNS) rats. Also rheogenic Na transport across the brush-border vesicles isolated from proximal tubular cells is faster. When erythrocytes and proximal tubular cells of MHS rats are compared to those of MNS rats, the former have smaller volume and Na content, whereas the Na transport is faster and the Ca ATPase at Vmax is lower. This indicates that the genetic cellular abnormality responsible for the renal functional abnormality and hypertension is also present in erythrocytes. Moreover, MHS erythrocyte abnormalities are genetically determined within the stem cells and are genetically associated with hypertension. Because a correlation was also found in human hypertension between erythrocyte Na transport abnormality and renal function, it is proposed that the erythrocyte may be used for studying the genetic molecular mechanisms of hypertension.

Animals↗
PubMed1986

A renal abnormality in the Milan hypertensive strain of rats and in humans predisposed to essential hypertension.

Many similarities in kidney-function abnormalities were found between hypertensive rats of the Milan strain (MHS) and young normotensive human subjects with hypertensive parents, compared with the appropriate controls. These similarities included an increased glomerular filtration rate, increased pressor effect of the kidney after transplantation, increased 24-h urinary output and lower plasma renin activity and urinary kallikrein. The isolated MHS kidney perfused in vitro with an artificial medium had a higher glomerular filtration rate, a higher urinary output, higher tubular sodium reabsorption and higher oxygen consumption than the kidney of control Milan normotensive rats (MNS). Further, reogenic sodium transport across brush border vesicles isolated from proximal tubular cells is faster in MHS than in MNS. Erythrocytes and proximal tubular cells of MHS have a lower volume and sodium content than those of MNS, while sodium transport is faster and the Ca2+-ATPase at Vmax is lower. This indicates that the 'genetic' cellular abnormality responsible for the renal-function abnormality and the hypertension is also present in erythrocytes. Thus these cells may be used to study the genetic cellular mechanisms of hypertension. Experiments with bone marrow transplantation and with F2 hybrids obtained by crossing the F1 (MHS X MNS) hybrids showed that the MHS erythrocyte abnormalities are genetically determined within the stem cells and are genetically associated with the hypertension. Since, in human hypertensives, there was a correlation between abnormal erythrocyte sodium transport and renal function, it is proposed that erythrocytes may be used in studying the cellular molecular mechanisms of hypertension.

Animals↗
PubMed1986

Antagonism of imidazole-induced shaking in the rat: a behavioural tool predictive of antidyskinetic activity?

In rats the intraperitoneal injection of imidazole (IMID) induced shaking behaviour, the effect appearing to be age- and sex-linked; younger animals responded less vigorously than older animals, while females always exhibited a significantly weaker response than males of the same age. After ovariectomy, however, the number of shakes of the two sexes was very similar. A number of drugs were examined for their antagonism of this highly reproducible syndrome. IMID-shakes were antagonized by reserpine, clonidine, high doses of B-HT 920, propranolol, haloperidol, morphine and diazepam, were not affected by apomorphine, (+)3-PPP, physostigmine, naloxone or methysergide, and were potentiated by sulpiride and scopolamine. The results are considered in the light of the possible neurochemical mechanisms underlying the IMID-syndrome; the suggested usefulness of this test for the study of human dyskinetic movements is disputed.

Aging↗
PubMed1985

Medroxyprogesterone acetate bioavailability after high-dose intraperitoneal administration in advanced cancer.

Administration of medroxyprogesterone acetate IP in advanced cancer with peritoneal metastases and ascitic effusion generates considerably higher drug plasma levels than those observed after PO or IM treatment. Comparison of areas under the time-concentration curves (AUC) with reference to the three administration routes indicates that after oral administration only 0.2%-17.4% (mean 5.7%; SD 3.77; 40 patients) of the administered dose is absorbed; after IM treatment a daily absorption of 0.7%-7.7% (mean 2.5%; SD 1.66; 30 patients) of the administered dose per injection site was computed.

Antineoplastic Agents↗
PubMed1985

Metabolic fate of zetidoline, a new neuroleptic agent, in man.

Healthy volunteers administered orally a single dose (20 mg) of [2-14C]zetidoline, a new dopamine antagonist, exhibited rapid absorption of radioactivity with peak plasma levels of 250-300 ng/ml achieved in 1 h. The compound underwent intensive metabolic first-pass so that plasma radioactivity was represented mostly by two products, metabolite B endowed with neuroleptic activity, and metabolite D inactive, while unchanged zetidoline was not detected. Disappearance of radioactivity from plasma was rapid with a half-life of 1.78 +/- 0.20 h. The simultaneous assay of plasma prolactin showed increased levels of the hormone (+ 464% at the peak time) up to the 6th h after dosing, with plasma concentration profile which mimic those of metabolite B. The radioactive test-dose was eliminated mainly via the kidneys with an average urinary recovery of 84.7 +/- 1.7% in 4 days (73.4 +/- 1.1% within 8 h). The main urinary metabolite (metabolite G) and two minor ones (metabolites B and D) were purified and their structures assigned by IR, MS and NMR spectroscopy, they are: 1-(3-chloro-4-hydroxyphenyl)-3 [2-(3,3-dimethyl-1-azetidinyl)ethyl]imidazolidin-2-one, metabolite B; 1-[2-(3,3-dimethyl-1-azetidinyl)ethyl]-imidazolidin-2-one, metabolite D and the 4'-O-sulphate ester of metabolite B, metabolite G. The metabolic fate of zetidoline in man follows the same phase I reactions demonstrated in rats and dogs, while the phase II reaction is sulphoconjugation instead of the glucuronidation observed in animals.

Adult↗
PubMed1985

Muscarinic cholinergic mediation of LHRH-induced LH and FSH secretion in normal men.

LHRH (100 micrograms i.v. bolus) was given to six young healthy men under basal conditions and after the administration of pirenzepine (10, 20, 30 or 40 mg i.v. 10 min before LHRH), which is a selective blocker of muscarinic cholinergic receptors. Pretreatment with 10 mg of pirenzepine did not modify LH and FSH responses to LHRH, whereas larger amounts of the drug significantly reduced gonadotrophin responses to LHRH. A dose-related effect of the drug was not observed, since a maximal reduction of LHRH-induced gonadotrophin secretion was already present when 20 mg of pirenzepine were used. When the effect of pirenzepine (20 mg) on the basal concentrations of FSH and LH was studied in four additional sex and age matched subjects, no significant changes were observed for at least 120 min after the injection. These results demonstrate that LHRH-induced LH and FSH secretion involves a muscarinic cholinergic mechanism.

Adult↗
PubMed1985

Metabolic pathways of the anti-hypertensive agent, N-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine+ ++ hydrochloride. I. Studies in the rat.

The metabolic fate of a new anti-hypertensive, 1-pyrrolyl pyridazinamine, was studied in male Wistar rats after both p.o. and i.v. administration (1 mg/kg). The compound undergoes rapid metabolism, disappearing from the central compartment with a half-life of about 0.5 h. Plasma concn. of the parent drug and its major metabolite I following i.v. and p.o. administration suggest a route-dependent first-pass metabolism. Ten metabolites were isolated from the urine and identified by u.v., i.r., mass and 1H-n.m.r. spectroscopy. The structure of some was confirmed by 13C-n.m.r. and chemical synthesis. All biotransformations are restricted to the pyrrole ring which undergoes oxidative cleavage followed by a series of chemical rearrangements. A minor pathway leads to the formation of methyl sulphinyl and methyl sulphonyl pyrroles. It is suggested that, as with natural indoles, the pyrrole might be oxidized by a 2,3-dioxygenase. The three major metabolites, I, II and IX, along with two minor ones, VI and VII, were inactive when tested i.v. for antihypertensive activity.

Administration, Oral↗
PubMed1985

Metabolic pathways of the anti-hypertensive agent, N-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine hydrochloride. II: Studies in the dog.

The metabolic fate of a new anti-hypertensive, 1-pyrrolyl-pyridazinamine, was studied in male Beagle dogs given both p.o. and i.v. doses of the 14C-labelled drug (1 mg/kg). The compound given as a single i.v. injection disappeared from the central compartment with a half-life of about 0.9 h. Plasma levels of total 14C were represented mostly by metabolites. Eight urinary metabolites designated as metabolites I, II and XI-XVI were purified and their structures assigned by means of u.v., i.r., n.m.r. and mass spectrometry. Quantitatively the primary metabolic attack involved the morpholine moiety of the molecule which undergoes oxidative opening. A minor pathway afforded the cleavage of the pyrrole followed by chemical rearrangements to form six-membered sidnone-like products or a triazole derivative. The major (XIII) and three minor metabolites were studied for their antihypertensive activity in rats and were shown to be inactive.

Administration, Oral↗