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Biomedical subjects

S Ripa

Publications and source records attributed to S Ripa.

At least 19 recordsLinked to original sources
PubMed1995

Antianginal and antiischemic efficacy of monotherapy extended-release nisoldipine (Coat Core) in chronic stable angina.

A double-blind, randomized, placebo-controlled study was conducted to test the peak and trough antianginal and antiischemic monotherapy efficacy and safety of a new extended-release formulation of nisoldipine (nisoldipine Coat Core [Bayer Corporation], 20 mg, 40 mg, and 60 mg once daily compared to placebo). Study patients had a history of chronic, stable angina pectoris, exercise-induced angina in association with ST segment depression, and exercise test reproducibility. Of the 483 patients enrolled in the study, results were valid for safety analysis for 312 and for efficacy analysis for 284. There was a statistically significant improvement in total exercise time at both peak and trough for patients taking 20 mg and 60 mg of nisoldipine compared with patients taking placebo, but the group taking 60 mg was not better than the group taking 20 mg (33.9 and 33.7 seconds, respectively, at trough). The results were similar for the secondary endpoints (time to onset of angina and time to 1 mm ST segment depression). No correlation was evident between plasma nisoldipine levels and total exercise duration. Headache and peripheral edema were the most frequently reported adverse events and were dose related. There were no discontinuations due to adverse events in patients randomized to the 20-mg nisoldipine group. No deaths occurred while patients were receiving active nisoldipine therapy. Therapy with this extended-release formulation of nisoldipine is an effective once-daily treatment for chronic stable angina pectoris. It represents one of the few dihydropyridine calcium channel antagonists that has shown efficacy when administered as monotherapy to patients with angina.

Adult↗
PubMed1995

Zinc and the elderly.

It is frequent in the elderly a zinc deficit, for many causes, which frequently occur in old age. Mineral deficit cause humoral and cellular immunity depression, with large increase of susceptibility to infections and increase of morbidity and mortality; besides it increases the proteinic malnutrition so frequent in old people. This condition is particularly presented in surgical patients and in patients undergoing total parenteral nutrition, when not specifically zinc supplemented. The evaluation of plasmatic zinc for diagnostic aims is scarcely significant, because hypoproteinemia (above all, hypoalbuminemia) is constantly present in old people: more useful and important is the leucocytic mineral evaluation, particularly in polymorphonuclear neutrophils. The average of recommended daily allowance of zinc is 15 mg for elderly people.

Aged↗
PubMed1995

[Zinc and diabetes mellitus].

In patients with type 1 and 2 diabetes was frequently found: low blood zinc levels, high zincuria, severe and ubiquitous cellular depletion of zinc, increased basal and after loading blood mineral clearance, and hyperglycaemia due to the reduction of pancreatic insulin secretion and to the reduced biological action of the hormone on liver, as a consequence of chronic zinc deficit. Strong endocellular zinc depletion in diabetics; low insulin secretion; insulin biological action decrease for zinc deficit; IG-I concentration decrease, that happens in this condition; insulin and IGF-I resistance; insulin and IGF-I receptors depletion in diabetics: are strong arguments for zinc pharmacological supplementation, in gastric protective formulation, to avoid gastroenteric problems.

Diabetes Mellitus, Type 1↗
PubMed1994

[Zinc and atherosclerosis].

The relationship between zinc and atherosclerosis is reviewed. Administration of strong doses of the mineral can turn out atherogenic through three mechanisms: 1. Through the alterations of the lipidic arrangement: decrease of HDL, increase of total cholesterol and LDL cholesterol (action promoted by the induced hypocupremia). 2. Through the alterations of the vasal wall, in consequence of the biochemical modifications of the basic substance (again, through secondary hypocupremia). 3. Through the increased platelet aggregation which seems to be produced by strong doses of zinc. In addition to these harmful actions, the antioxidative action, typical of zinc, must be stressed, which prevents oxidation of LDL and consequently stops the main mechanism of atherogenesis. Besides, the mineral restricts and nullifies the loss of metallothionein in zinc, produced by free radicals and subsequent functional alterations. Moreover, the calcium antagonist action of zinc must be considered: it blocks calcium and its several favorable actions on atherogenesis. In consideration of these last aspects, the rule of zinc, in suitable doses, could be considered as basic in the context of a strategy of prophylaxis and therapy of the atherosclerosis process.

Adult↗
PubMed1994

[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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗