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Biomedical subjects

J Santoro

Publications and source records attributed to J Santoro.

11 recordsLinked to original sources
PubMed1979

Carbon-13 NMR investigations on ribonuclease A.

The proposed interaction between the amino acid residues Asp 14 and His 48 of ribonuclease A has been confirmed by 13C-NMR spectroscopy. The titration behaviour of the resonance of the side-chain carboxyl group of Asp 14 suggests a pKa of 6.5--7.0 for His 48. An equilibrium between different conformation process of His 48. Upon this deprotonation a hydrogen bond between the side-chains of Asp 14 or His 48 and Tyr 25 seems to be formed as is suggested by the behaviour of a tyrosine C zeta resonance assigned to Tyr 25. One phenylalanine resonance broadens and moves upfield on the addition of the inhibitor Cyd-2'-P, being therefore assigned to Phe 120. The behaviour of this resonance suggests that the upfield shift results from the anisotropy of the cytidine ring. Three signals are assigned to the three Phe residues.

Animals↗
PubMed1979

In vitro activity and pharmacokinetics of cefaclor in normal volunteers and patients with renal failure.

In both Mueller-Hinton agar (MHA) and antibiotic medium no. 1 (AB1) cefaclor was more active than cephalothin or cephalexin against Enterobacteriaceae. Its activity was equivalent to cephalexin against S. aureus in MHA. Cefaclor was particularly active against P. mirabilis. The activity of this antibiotic was greated in AB1 than in MHA. The inoculum effect was pronounced for cefaclor when compared with cephalothin, but cefaclor retained greater activity even against the higher inoculum. In volunteers with normal renal function, cefaclor produced slightly lower blood levels than those reported for cephalexin. Absorption after eating was decreased and delayed. Despite severe renal failure, substantial urine levels of antibiotic were still achieved. In contrast to cephalexin, plasma half-life for cefaclor was only moderately prolonged by renal failure (two-to-threefold) and only minimally shortened by haemodialysis. Adequate concentrations of cefaclor in sputum, active against common respiratory pathogens, could not be consistently demonstrated after the oral administration of a 1 gram dose of cefaclor.

Adult↗
PubMed1978

13C NMR investigations on Npi-[13C1]carboxymethyl-histidine-119 ribonuclease.

The ribonuclease A derivative Npi-[13C1]carboxymethyl-histine-119 ribonuclease prepared by using [13C1]bromoacetate as alkylating reagent has been investigated with high resolution 13C NMR spectroscopy. In the 13C NMR spectra two carbon resonances of relatively high intensity appear which can be assigned to carboxyl groups attached to His-119 and Met-30, their intensity ratio being 10 : 1. The pH dependence of the carbon resonance of the carboxy-methyl group bound to the Npi of His-119 differs in the absence and presence of Cyd-2'-P, thus indicating that the catalytically inactive derivative does bind nucleotides. A mechanism of the alkylation reaction at pH 5.6 is proposed in which the epsilon-amino group of Lys-41 acts as the binding site for the carboxyl group of bromoacetate pushing the bromomethylene group towards the Npi of His-119 or the Ntau of His-12.

Histidine↗
PubMed1978

Treatment of experimental Staphylococcus aureus endocarditis: comparison of cephalothin, cefazolin, and methicillin.

The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactamase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and one-eighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.

Animals↗
PubMed1978

Pharmacology and efficacy of netilmicin.

Twenty-six patients, 20 to 77 years of age, were treated with netilmicin, mean dose 2 mg/kg every 8 h intramuscularly or in a 20-min intravenous infusion. The mean serum half-lives in patients with creatinine clearances of >/=90 ml/min and 60 to 90 ml/min were 3.2 and 3.4 h, respectively. In patients with serum creatinines of </=1.4 mg/100 ml and creatinine clearances of >/=60 ml/min, mean serum levels were 9.0 and 1.2 mug/ml, respectively, 5 to 15 min and 7.5 h post-intravenous infusion, and 7.1 and 1.7 mug/ml, respectively, 1 and 8 h post-intramuscular injection. Twenty-five patients had acute pyelonephritis; 7 of the 25 had bacteremia. The infecting bacteria were Escherichia coli (15), Proteus mirabilis (5), Pseudomonas aeruginosa (2), Klebsiella pneumoniae (1), Enterobacter hafniae (1), and both Proteus rettgeri and Proteus morganii (1). All were inhibited by 6.3 mug of netilmicin per ml, except for the P. rettgeri, which required 25 mug/ml for inhibition. Of 23 patients who could be evaluated, 19 were bacteriologically and clinically cured at follow-up. Of the remaining four, one relapsed, two became reinfected, and one was lost to follow-up. Five patients developed nephrotoxicity; two of the five had previous renal insufficiency. Three patients, one with abnormal renal function, developed ototoxicity detected only with audiograms. These studies suggest that netilmicin is effective in serious gram-negative bacillary infections, but is nephrotoxic and ototoxic in humans.

Adult↗
PubMed1978

Pharmacology of cefaclor in normal volunteers and patients with renal failure.

After a 500-mg dose of cefaclor, the mean peak plasma level was 12.4 mug/ml and after a 250-mg dose it was 5 mug/ml in normal volunteers. Food intake significantly reduced absorption. Probenecid prolonged plasma levels. Mean plasma half-life in normal volunteers was 0.8 h. Only about 50% of the dose was excreted in the urine within 4 h in normal volunteers. Plasma half-life in patients with renal insufficiency was only about 3 h, which suggests that cefaclor may be eliminated by nonrenal mechanisms in humans. Urinary levels of cefaclor were adequate to inhibit susceptible pathogens even in patients with moderately severe renal failure. Plasma half-life during hemodialysis was 2.1 h and rose to 2.8 h after dialysis.

Adult↗
PubMed1978

Rat model of experimental endocarditis.

A simple model of infective endocarditis was produced in rats. With the aid of a guide wire, polyethylene catheters were passed into the left ventricle through the right carotid artery of Sprague-Dawley rats weighing 300 to 350 g. A volume of 1 ml of an overnight culture of Streptococcus mitis, Staphylococcus aureus, or Streptococcus faecalis was intravenously injected 1 to 2 days after catheterization. Bacterial titers of Streptococcus mitis in vegetations were about 10(4)-fold greater than in other tissues. Blood cultures were always positive after 6 h. Mortality was 19% at 1 week and 82% at 2 weeks. Catheters were pulled 24 h after infection, and vegetation titers of greater than 7.0 log10 colony-forming units per g were sustained at 5 days. In intravenously infected rats without catheters, blood and tissues were sterile after 3 to 5 days. With Staphylococcus aureus, vegetations had greater than 9.0 log10 colony-forming units and with Streptococcus faecalis 8.8 +/- 0.3 log10 colony-forming units per g at 2 days. The rat model of infective endocarditis should prove to be suitable for further pathological and therapeutic studies.

Animals↗
PubMed1977

In vitro activity and clinical efficacy of clindamycin in the treatment of infections due to anaerobic bacteria.

Clindamycin, rosamicin, josamycin, and metronidazole had similar inhibitory activity against 29 clinical isolates of Bacteroides fragilis, i.e., 100% of strains were inhibited by 0.8 microng of metronidazole or josamycin/ml and 100% by 1.6 microng of clindamycin or rosamicin/ml. Metronidazole was bactericidal against 97% of the isolates, and clindamycin or rosamicin (in concentrations of 1.6 microng/ml) was bactericidal against 80%. Erythromycin and josamicin were the least bactericidal agents in vitro. Thirty-two patients with pleuropulmonary and intraabdominal or pelvic infections caused by anaerobic bacteria were treated with clindamycin. Cure was achieved in 27 patients. In another group of 37 patients treated with parenteral clindamycin, diarrhea developed in 30% and was significantly more common in those patients with abdominal or pelvic infection. Only one patient developed pseudomembranous colitis. These observations suggest that clindamycin is an excellent and relatively safe antibiotic for treatment of infections caused by anaerobes when combined with surgery or with other antibiotics selected for activity against aerobic gram-negative bacilli.

Aminoglycosides↗
PubMed1977

In vitro activity of cefaclor, a new orally administered cephalosporin antibiotic.

The in vitro antibacterial activity of cefaclor, cephalothin, and cephalexin against 261 clinical isolates of Staphylococcus aureus and Enterobacteriaceae was compared. Cefaclor and cephalexin were about equally active against S. aureus. Cefaclor was the most active cephalosporin against Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. The effect on the antimicrobial activity using a relatively high and low inoculum was pronounced for cefaclor when compared with that of cephalothin.

Bacteria↗