[Experimental studies on the passage of CS-1170 into the cerebrospinal fluid (author's transl)].
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Biomedical subjects
Publications and source records attributed to T Haruta.
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Broadcillin 'Banyu', which contains an equal amount of ampicillin and oxacillin was given intravenously to children with acute bacterial infections and the following results were obtained. 1. Patients were 55 children with the following bacterial infections; respiratory tract infections (8 cases), pneumonia (34), sepsis (1), meningitis (1), cutaneous and subcutaneous suppurative inflammation (5), osteomyelitis (1), urinary tract infection (2), enteritis (1), and chemoprophylaxis (2). They ranged in age from newborns to 8 year old, but most of them were infants. In the majority of the patients, broadcillin 'Banyu' was administered 50 approximately 150 mg/day in three to four equally divided doses by one shot-injection or by a continuous drip infusion for a period of 2 approximately 10 days. The overall efficacy rate was 88.7% in 53 cases after two cases of chemoprophylaxis were excluded, i.e., excellent in 28, good in 19 and failure in 6: excellent in 4 and good in 4 in 8 cases of respiratory tract infections; excellent in 20, good in 11 and failure in 3 in 34 cases of pneumonia (an efficacy rate 91.2%); failure in sepsis and meningitis: excellent in 2 and good in 3 in 5 cases of cutaneous and subcutaneous suppurative inflammation; excellent in osteomyelitis; excellent in 1 and good in 1 of 2 cases of urinary tract infection; failure in enteritis. 2. Adverse reactions were noted on 10 occasions in 9 cases (16.4%), including 1 case of skin eruption, 1 case of eosinophilia, 5 cases of slight elevation of GOT, 1 case of slight elevation of GPT and 2 cases of slight elevation of BUN. 3. Based on the above results, it was concluded that clinical effect of broadcillin 'Banyu' by an intravenous administration is comparable to its intramuscular route and that safety of intravenous usage seems to be verified as long as the above described dosage is followed.
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Passage of cephaloridine, cephalothin and cefazolin into cerebrospinal fluid (CSF) was evaluated in Staphylococcus aureus meningitis in rabbits and the following results were obtained. 1. Concentration in CSF (microgram/ml) [CSF/serum ratio (%)] was determined 1/2, 1 and 2 hours after a single intravenous injection of 100 mg/kg of each antibiotic, respectively; cephaloridine-7.5 [8.9], 9.7 [13.8], 9.1 [22.6]; cephalothin-0.42 [3.6], 0.23 [6.4], not detectable [0]; cefazolin-7.5 [11.8], 5.2 [19.3], 2.0 [17.5]. 2. When results with cefazolin after an intravenous injection 100 mg/kg and 200 mg/kg were compared, a definite dose response was noted in blood concentration but not in CSF concentration. 3. A standard error of CSF concentrations of each antibiotic was larger than that of penicillins, and "Unpredictability" of their passage into CSF was considered to be one of the characteristics common to these three drugs in respect of their passage into CSF. 4. There was no significant difference noted in antibiotic passage into CSF between cephaloridine of low protein binding rate and cefazolin of very high binding rate. Cephalothin, of which binding rate was intermediate, showed a remarkably lower passage into CSF. These results indicate that a correlation does not always exist between protein binding rate of the antibiotics and their passage into CSF. 5. Based on the above results, a review of the literature was made on clinical applicability of these three antibiotics in the treatment of bacterial meningitis. Low transport rate of cephalothin into CSF and nephrotoxicity of cephaloridine make them to be unsuitable for bacterial meningitis. Cefazolin is considered to be suitable in the treatment of ampicillin-resistant Escherichia coli meningitis and Gram-positive coccal meningitis in which penicillins are not applicable.
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The metabolism of a mutant insulin, [LeuB25]-insulin, was studied in vitro and in vivo. Porcine or mutant insulin (4 micrograms/kg body weight) was injected i.v. into streptozotocin-induced diabetic rats and their plasma glucose and insulin levels were determined. The half-lives of porcine and mutant insulin were 3 min and 18 min, respectively. The ability of the mutant insulin to lower the blood glucose levels was 38% of that of normal when the glucose levels at the nadir were compared. Receptor-mediated degradation of the mutant insulin assessed by chromatography of the degraded materials in the media after incubation with cells was less compared with that of porcine insulin (4% vs. 24%). The media containing the insulin degrading enzyme (IDE) of IM-9 cells and rat livers degraded porcine and mutant insulin to the same extent. These results suggest that the decreased clearance of insulin is due to the decreased receptor binding and the decreased receptor-mediated degradation, but is not due to the decreased degradation by IDE.