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Biomedical subjects

S Ripa

Publications and source records attributed to S Ripa.

At least 37 records · Page 2Linked to original sources

[Zinc and arterial pressure].

There are complex relations between zinc and arterial pressure. The mineral, which enters in the composition of zinc-enzyme "angiotensin-converting-enzyme" (ACE), takes part in arterial pressure regulation also through influences on others hormonal systems, which carry on many complex actions on circulation (glucocorticoids, catecholamines). It is frequent to find in hypertensive subjects low levels of plasmatic zinc (and high of cadmium): in "essential" hypertensive patients, particularly, it would be present a primary genetic defect leading, through transmembrane desregulation of ionic pumps, to high intracellular zinc and, secondarily, to high intracellular calcium. On the other hand, the same hypertensive process causes zinc and copper metabolism modifications, with an increase in zinc tissue concentration (opposite behaviour of copper). Moreover the plasmatic zinc reduction causes a proportional decrease of plasmatic and tissue ACE activity and arterial hypotension: zinc administration, in vitro and in vivo, clearly increases ACE action, with normalization of altered parameters due to zinc deficit.

Blood Pressure↗

Survey of clinical isolates of Staphylococcus aureus for borderline susceptibility to antistaphylococcal penicillins.

On the basis of the MICs of methicillin and oxacillin, 975 clinical isolates of Staphylococcus aureus were categorized as having resistance, borderline susceptibility or full susceptibility to penicillinase-resistant penicillins (PRPs). The borderline phenotype accounted for 122 isolates (12.5%), whereas 562 isolates were fully susceptible and 290 resistant; one remaining isolate had resistance to methicillin and borderline susceptibility to oxacillin. Reductions in the MICs of methicillin and oxacillin in the presence of sulbactam were greater in strains with borderline PRP susceptibility than in fully susceptible or resistant isolates. Over 99% of fully PRP-susceptible strains, 93% with borderline susceptibility and 71% of resistant strains were susceptible to ampicillin/sulbactam. The production of beta-lactamase, assayed in all strains using nitrocefin as substrate, could be detected without prior induction in 729 strains and after induction only in another 156 strains. With only two exceptions, the beta-lactamase negative strains were part of the fully PRP-susceptible group of organisms (88 of 562 isolates). Among the borderline isolates, strong beta-lactamase reactions were encountered with particular frequency, but not in all strains and not exclusively in borderline strains. Although associated with the majority of borderline strains, beta-lactamase hyperproduction thus did not appear to be an essential feature of the borderline phenotype. The results obtained may have implications for laboratory and clinical medicine, also in the light of recent findings suggesting that other mechanisms besides beta-lactamase hyperproduction may account for borderline susceptibility to PRPs.

Ampicillin↗

Pharmacokinetics of fluconazole in normal volunteers.

The pharmacokinetic profile of fluconazole, after 100 mg i.v. infusion or oral administration of a single 50 mg or 150 mg dose, was investigated in 18 healthy volunteers. At a dose of 100 mg i.v., the half-life (t1/2 beta) was 29.73 +/- 8.05h. The mean residence time in the plasma was 27.56 +/- 5.98 h. The post-distributive volume V beta = 52.16 +/- 9.83 l, approximating that of total body water. Renal excretion accounted for 61.64 +/- 8.80% of the drug elimination after 48 h, with renal clearance Clr = 12.91 +/- 2.83 ml/min. Plasma clearance (Clp) was 21.03 +/- 5.07 ml/min. At oral doses of 50 and 150 mg the distribution and elimination of fluconazole resembled that following i.v. infusion. The peak levels in plasma at 2.5 h were 0.93 +/- 0.13 and 2.69 +/- 0.43 micrograms/ml, respectively. The large distribution volume, the long half-life and mean residence times, combined with a rapid absorption after oral administration, suggest that fluconazole will be effective at a wide range of body sites.

Administration, Oral↗

Bacteriolytic effect of teicoplanin.

The glycopeptide antibiotic teicoplanin belongs to the same group as vancomycin and ristocetin and is a valuable tool for studying the autolytic system of sensitive Gram-positive bacteria. Teicoplanin, at a concentration of 1 microgram ml-1, caused rapid lysis of exponential phase cells of Streptococcus faecalis. Bacillus spp. were most sensitive to the antibiotic; effective lysis occurred at 0.1 microgram teicoplanin ml-1. The bacteriolytic effect depended on the antibiotic concentration, the growth phase and growth rate of the target organism. Antibiotic added to overnight cultures did not cause lysis. Mg2+ (50 mM) was unable to prevent lysis. Mutants with decreased autolytic activity were more resistant to teicoplanin and lysed more slowly than the wild-type. Growth of bacteria in slightly acidic medium protected the cells against the lytic effect of teicoplanin typically observed at pH 7 or 8. This pH-dependent antibiotic tolerance was demonstrated with both bacilli and streptococci. Bacterial lysis was prevented by the presence of Ac-L-Lys(Ac)-D-Ala-D-Ala and normal growth was observed when this peptide was added simultaneously with teicoplanin. Bacteria pretreated with teicoplanin, washed and transferred to fresh medium or buffers behaved as if the antibiotic was still present; in neutral or slightly alkaline conditions strong lysis occurred, whereas in acidic buffer only bacteriostasis was observed. In contrast to vancomycin, teicoplanin induced some lysis of bacteria in hypertonic media, presumably by affecting the integrity of the cell membrane.

Amino Acid Sequence↗

In vitro activity of sulbactam/ampicillin against ampicillin-resistant, beta-lactamase-producing bacteria isolated in Italian hospitals.

A multicenter study aimed at assessing the in vitro activity of sulbactam/ampicillin against a wide range of bacterial pathogens was performed using 2,209 clinical strains, all recently collected from inpatients in seven Italian centers and preliminarily screened as being ampicillin-resistant and beta-lactamase producers. In comparative disk diffusion trials using 8 large-spectrum antimicrobials, the percentage of resistance to sulbactam/ampicillin in staphylococci was similar to the percentage of resistance to netilmicin and lower than to the other antibiotics; with gram-negative bacteria, only netilmicin, ofloxacin, and, less consistently, cefotetan showed lower incidences of resistance. The minimal inhibitory concentrations (MICs) of ampicillin alone and sulbactam/ampicillin together were determined using the agar dilution method. The Enterobacteriaceae strains which shifted to ampicillin susceptibility in the presence of sulbactam averaged 68%, but values significantly above or below average were observed in some genera of this family. The percentage of strains which the presence of sulbactam rendered ampicillin-susceptible in vitro reached 97% in Haemophilus strains and 100% in branhamellae and gonococci. High percentages were also recorded in staphylococci, with a peak of 100% in oxacillin-susceptible Staphylococcus aureus strains. In general, center-to-center differences were relatively limited.

Ampicillin↗

Pharmacokinetics of sulbactam/ampicillin in humans after intravenous and intramuscular injection.

We investigated the pharmacokinetic properties of sulbactam/ampicillin (S/A), after intravenous (0.5/1.0 and 1.0/2.0 g) and intramuscular (0.5/1.0 g) coadministration in 10 male subjects. After 1.0/2.0 g intravenous doses of S/A the half-lives (t1/2 beta) were 1.14 +/- 0.14/1.09 +/- 0.16 h. The values for plasma clearance (CLp) were 198.83 +/- 26.27/250.33 +/- 39.28 ml/min and the renal clearance (Clr) 173.50 +/- 19.66/208.80 +/- 26.43 ml/min. The post distributive volumes (V beta) were 19.67 +/- 3.24/23.56 +/- 5.76 liters. Similar values were obtained after 0.5/1.0 g of S/A intravenous coinjection. After 0.5/1.0 g intramuscular coadministration the t1/2 beta values were 1.26 +/- 0.18/1.20 +/- 0.15 h. The values for Clp were 208.00 +/- 28.73/243.17 +/- 33.24 ml/min, for Clr 179.50 +/- 20.26/202.67 +/- 27.61 ml/min and for V beta 22.27 +/- 4.12/25.30 +/- 4.87 liters. The renal clearance of sulbactam is comparable to that of ampicillin and both clearances are greater than the glomerular filtration rate, suggesting active renal tubular secretion of the two drugs. The large volumes of distribution, and the ratio K12/K21 = 0.5 show the extensive distribution of the two drugs into extracellular fluids. The very similar values of the pharmacokinetic parameters of sulbactam and ampicillin confirm that the kinetics of the two drugs closely resemble one another.

Adult↗

Pharmacokinetics of bacampicillin using a compartment model with zero-order absorption.

The pharmacokinetics of bacampicillin, a prodrug of ampicillin which is absorbed from the gastrointestinal tract, were studied in 10 healthy male volunteers after administration of 1,200 mg in a single oral dose. The pharmacokinetic analysis was carried out by applying a single-compartment kinetic model with zero-order absorption. The apparent duration of absorption (T) was about 1 h for all subjects. The peak plasma concentrations (Cmax) were 17.89 +/- 1.82 micrograms/ml, and the mean plasma half-life during beta-phase was 1.17 +/- 0.14 h. The area under the curve was 41.22 +/- 5.29 micrograms.h/ml. The mean urinary recovery during 24 h amounted to 76.4 +/- 3.65% of the dose.

Adult↗

Pharmacokinetics of teicoplanin.

We investigated the pharmacokinetic properties of teicoplanin, after 200 mg i.v. and i.m. administration in 10 healthy male subjects by assuming a three-compartment open model with elimination from the central compartment. The mean peak plasma level was 7.16 micrograms/ml reached after 2.26 h. The half-life, the plasma and renal clearances, evaluated from i.v. data were 44.49 h, 15.31 and 9.08 ml/min, respectively. The same parameters after i.m. administration were 45.62 h, 15.31 and 9.46 ml/min. The estimates of creatinine clearance (Clcr greater than 80 ml/min), renal clearance and the low free fraction (fB approximately equal to 0.1) suggested a tubular reabsorption, FR, of the drug. The distribution volume at steady state after i.v. and i.m. administration (Vss = 41.29 and 44.76 litres) were nearly total body water. Bioavailability of the drug (F = 92.4%) showed an almost completely absorption of teicoplanin after i.m. administration. Urinary recovery was 49.6 and 47.9% of the dose after i.v. and i.m. administration, respectively.

Adult↗

Comparative activity in different media of ketoconazole, miconazole and amphotericin B against Candida lusitaniae and sucrose-negative Candida tropicalis.

This study evaluates the susceptibility of sucrose-negative Candida tropicalis and Candida lusitaniae strains to amphotericin B (AMB), miconazole (MCZ) and ketoconazole (KTZ). The susceptibility tests were carried out in different media: Antibiotic Medium 3 (AM-3m) and Earle Minimum Essential Medium (E-MEM) for AMB: Yeast Nitrogen Base (YNB) and E-MEM for imidazole compounds. The minimal fungicidal concentrations (MFCs) of AMB were slightly higher than minimal inhibitory concentration (MICs) except against Candida lusitaniae strains; whereas the MFCs of MCZ and KTZ were higher than the MICs by almost two-fold for all strains tested. AMB was more efficacious against sucrose-negative Candida tropicalis and the MICs were very definite; on the contrary, the MICs with KTZ were difficult to read. The MICs of AMB in E-MEM were essentially the same as those in AM-3m; whereas for KTZ and MCZ determined in YNB the MICs were generally higher than those obtained in E-MEM.

Amphotericin B↗

In vitro antibacterial activity of rifaximin against Clostridium difficile, Campylobacter jejunii and Yersinia spp.

Fifty-four isolates of Campylobacter jejunii, 91 isolates of Yersinia spp. and 56 isolates of Clostridium difficile, recovered from stools of patients with diarrhoea or other intestinal disturbances and from stools of asymptomatic patients receiving antibiotic therapy, were tested in vitro for susceptibility to rifaximin, rifampicin and neomycin. The in vitro antibacterial activities were found to be comparable against the aerobic bacterium; on the contrary, against microaerophilic and anaerobic bacteria rifaximin and rifampicin were much more effective than neomycin.

Campylobacter↗

Pharmacokinetics of cefotetan in elderly subjects after intramuscular administration.

The pharmacokinetics of cefotetan were studied in 10 healthy male subjects 65-75 years of age with normal liver function and a creatinine clearance of greater than 80 ml/min after single 2 g intramuscular doses. The mean plasma level at 0.5 h was 52.50 +/- 9.16 micrograms/ml. Peak concentrations were 91.78 +/- 12.02 micrograms/ml at 3 h, declining to 10.33 +/- 2.18 micrograms/ml at 18 h, 4.0 +/- 1.12 micrograms/ml at 24 h after the start injection. The percentage of the dose recovered in urine (0 to 24 h) was 60.3%. Cefotetan plasma clearance showed a statistically significant correlation (r = 0.956, p less than 0.001) with measured creatinine clearance and the positive intercept ordinate confirmed a nonrenal clearance of the drug (biliary excretion). The normal age-related changes in cefotetan kinetics were relatively small and dosage adjustment was not necessary for normal elderly subjects requiring cefotetan.

Aged↗

Sulbenicillin: pharmacokinetics and penetration into bronchial secretion in elderly patients.

This study evaluates the pharmacokinetics of sulbenicillin (alpha-sulfobenzylpenicillin) in elderly subjects after single and multiple doses and the penetration into bronchial secretion in elderly patients with chronically superinfected bronchial pathology. Peak plasma levels were 53.34 micrograms/ml (group I); 55.80 and 57.82 micrograms/ml (group II) after 1 h. The half-life (t 1/2 beta) was 1.47 h (group I); 1.49 and 1.62 h (group II). Renal clearance was 6.68 l/h; 6.25 and 5.44 l/h; whereas the volume of distribution was 18.02 l; 17.84 and 17.21 l for groups I and II respectively. The mean percentage of the recovered active drug in urine over 12 h was 77.72% of dose. The mean peak reaching the bronchial secretion was 3.60 micrograms/ml at the 4th hour. The results of the multiple dose study indicated that there was no apparent change in the distribution or elimination kinetics of sulbenicillin after 2 g i.m. administration. Thus, the kinetics from the multiple dose study were in close agreement with those from the single dose study and no accumulation of sulbenicillin was observed. This study provided satisfactory results and confirmed the significant presence of sulbenicillin into bronchial secretions.

Absorption↗

Antibodies anti-HTLV III and lymphocyte subsets of high risk subjects.

208 assay for the research into anti-HTLV III antibodies and lymphocytes subsets were carried out on the same number of patients at risk. 11 homosexual man, 143 intravenous drug users (i.d.u.) and 3 children of drug addicts from hospitals in the Marche and Abruzzo and 51 haemophiliacs from hospital in Florence were examined. 3 determination of anti-HTLV III antibodies were taken from each subject using 3 different commercial Kits. The results concur with and confirm similar epidemiological studies that have been done. The haemophiliac group had the highest positive percentage (39.2%), then came i.d.u. (11.9%) and the homosexuals (10.0%). Furthermore, of the 38 positive totals, there were 22 with only one kit, 18 with two, and 15 with all three. The evaluation of the lymphocyte subsets did not strictly correlate with the presence of the antiretrovirus antibodies.

Acquired Immunodeficiency Syndrome↗

Pharmacokinetics of cefoperazone after single and multiple doses.

The pharmacokinetics of cefoperazone was determined following single and multiple intravenous and intramuscular administrations in man. Ten subjects at each dose level were given eleven successive doses, at 12 h intervals of 500 and 1000 mg i.m. and i.v.. Serum concentrations and urinary excretion were determined in all subjects after the first, fifth and eleventh doses. The first i.m. doses yielded mean peak serum levels of 37 micrograms/ml and 76 micrograms/ml at 1.0 h after injection. The first i.v. doses yielded mean serum levels of 93 and 180 micrograms/ml at 5 min after the injection. No tendency toward drug accumulation was observed on multiple dosage. The pharmacokinetics could be described by a linear, open, two-compartment model of drug distribution. The terminal serum half-life (2.1-2.4 h after i.v. doses and 2.6-2.8 h after i.m. doses) remained essentially constant over the period of the study by dose levels. The no-significant differences of areas under the curve between the two routes, at two doses, show the absolute bioavailability of cefoperazone was about 95% following i.m. administration. The high binding to serum proteins (90%) influences favourably the pharmacokinetic parameters of cefoperazone. It yielded high and prolonged serum concentrations and has very useful distribution properties. These favourable properties, together with its good antibacterial activity, suggest that cefoperazone will be effective in treating bacterial infections in human beings.

Adult↗

Determination of cefatrizine levels in blood, tonsils, paranasal sinuses and middle ear.

Levels of cefatrizine, a new oral cephalosporin, were determined in blood and in tonsils, paranasal sinus secretions and middle ear exudates from 18 patients with acute infections at these sites. Three and six hours after administration of 500 mg cefatrizine satisfactory levels of the antibiotic were found at all the sites examined. Levels in the tonsils and middle ear were higher than those in blood, while lower levels were recorded in nasal secretions.

Bacterial Infections↗

[Production of coagulase and thermonuclease in 366 strains of staphylococci belonging to different lyogroups].

366 human staphylococci were tested for the production of coagulase and thermonuclease and were subdivided into lyogroups. 98% of the isolates showed uniformly positive or uniformly negative results for the production of two enzymes. All uniformly positive strains belonged to the species Staphylococcus aureus, whereas coagulase-thermonuclease negative strains were easily subdivided into five lyogroups. Seven strains produced only one of two enzymes and were identified by analysis of their bacteriolytic activity. Two of these strains were identified as Staphylococcus aureus, one was coagulase negative and the other thermonuclease negative.

Coagulase↗

Pharmacokinetics of cefatrizine after oral administration in human volunteers.

The oral bioavailability of cefatrizine was studied in four groups, each of ten healthy young male volunteers. Capsules and suspension formulations were each administered at doses of 250 and 500 mg. Both the capsules and suspensions had mean peak plasma levels at 1.6 h at both dose levels. Mean peak plasma levels were 4.1 and 4.3 micrograms/ml for the 250 mg capsule and suspension doses respectively and 7.1 and 7.5 micrograms/ml for the 500 mg capsules and suspension doses respectively. The overall mean half-life was 1.7 h. For both types of formulations and at both dose levels 63-65% of the doses were excreted in the urine as intact cefatrizine, 85% of this amount within 8 h. The overall mean renal clearance was 157 ml/min. The cefatrizine capsule and suspension formulations were completely bioequivalent in regard to both rate and extent of bioavailability. Plasma concentrations and urinary recoveries of cefatrizine were higher than those previously reported, due to precautions taken in sample collection and storage.

Administration, Oral↗