[Pharmacokinetic, bacteriological and clinical studies on biapenem (L-627) in children].

The results are summarized as follows: 1. A total of 10 patients were treated with biapenem (L-627). We received informed consent from all of their parents. Each dose was 6 mg/kg, and it was administered 3 times daily (40 mg/kg, 4 times daily in meningitis), in a 30-minute intravenous drip infusion for 5-17 days. The clinical efficacies of L-627 in 10 patients with bacterial infections (1 with purulent meningitis, 1 with sepsis, 5 with pneumonia, 2 with urinary tract infection and 1 with purulent tonsillitis) were evaluated as excellent in 8 patients, as good in 2 patients with an efficacy rate of 100%. Seven causative organisms found in 5 patients (Streptococcus pneumoniae in 2, Moraxella (Branhamella) catarrhalis in 2, Haemophilus influenzae in 2 and Pseudomonas aeruginosa in 1) were eradicated. No adverse reaction was observed in any of the 10 patients. 2. Pharmacokinetic studies Peak plasma concentrations of L-627 were 12.5-13.7 micrograms/ml at the dose of 6 mg/kg administered by 30-minute drip infusion. Plasma half-lives of L-627 in the beta-phase averaged 0.72 hour (0.63-0.80 hour). CSF concentration/plasma concentration ratios of L-627 were 1.12/8.16 micrograms/ml (Day 2, 1.17 hours after at dose of 20 mg/kg), 0.88/3.44 micrograms/ml (Day 3, 4.0 hours after at dose of 30 mg/kg) and 0.68/5.12 micrograms/ml (Day 13, 3.0 hours after at dose of 40 mg/kg) administered by 30-minute drip infusion in the child with purulent meningitis (case 1).(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacokinetic, bacteriological and clinical studies on S-1108 in children].

Pharmacokinetic, bacteriological and clinical studies on S-1108 were performed in children. The results were as follows: 1. A total of 11 patients were treated with S-1108. Each dose was 3 mg/kg, orally administered 3 times daily for 4-14 days. The clinical efficacies of S-1108 in 10 patients with bacterial infections (1 with bacteremia, 4 with pneumonia, 1 with acute maxillary sinusitis, 1 with scarlet fever and 2 with streptococcal pharyngitis) were evaluated as excellent in 8 patients and as good in 2 patients with an efficacy rate of 100%. Only one patient with staphylococcal scalded skin syndrome due to methicillin resistant Staphylococcus aureus (MRSA) who received gamma-globulin was not evaluated. Fourteen causative strains of 5 species were found in 10 patients. Three strains of Streptococcus pneumoniae out of 5, 2 of 3 Branhamella catarrhalis strains, none of Staphylococcus aureus and all 3 strains of Streptococcus pyogenes were eradicated. No adverse reaction was observed in any of the 11 patients. 2. MICs of S-1108 against 5 clinically isolated S. pneumoniae from cases of infections were examined. All of them were relatively highly resistant to penicillins. S-1108 was compared with cefteram pivoxil, cefpodoxime proxetil, cefaclor and cefixime, and it showed better antibacterial activity or than other cephems. 3. Double peaks were obtained in plasma levels of S-1108 orally administered at a dose of 3 mg/kg at 30 minutes after meal and were 1.03 microgram/ml and 0.74 microgram/ml at 1 and 4 hours after administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Mammalian subtilisin-related proteinases in cleavage activation of the paramyxovirus fusion glycoprotein: superiority of furin/PACE to PC2 or PC1/PC3.

The fusion glycoprotein precursor of Newcastle disease virus is ubiquitously cleaved in the constitutive secretory pathway if it possesses an oligobasic cleavage motif (RRQR/KR), whereas the precursor is refractory to cleavage if the motif is monobasic (GR/KQGR). We examined the cleavage activity of the mammalian subtilisin-related proteinases furin/PACE, PC2, and PC1/PC3, which are thought to be responsible for proprotein processing in either the constitutive (furin/PACE) or the regulated (PC2 and PC1/PC3) secretory pathway, for the viral precursors with different cleavage motifs. Only furin/PACE was fully capable of cleaving the precursors with the oligobasic motif. PC2 and PC1/PC3 were incapable or only partially capable of cleaving at this motif. None of the proteinases cleaved the monobasic motif. These results suggest involvement of furin/PACE in viral protein processing in the constitutive secretory pathway.

Magnificent expression of asialo GM1 on thymus cells and spleen T cells of the musk shrew, Suncus murinus.

The expression of asialo GM1 (GA1) was observed on almost all thymocytes from young musk shrew, at the age of 4 weeks by flow cytometric analysis. In adult shrew aged 10 months, the ratio of GA1-negative thymocytes was increased. Among several anti-glycolipid antibodies used, anti-GM1 and anti-Forssman also reacted with the thymocytes. Protein fraction of the thymocytes was analyzed by SDS-PAGE followed by immunoblotting. Anti-GA1 and anti-GM1 showed two bands and one band, respectively, however, their mobilities were different from each other. Anti-Forssman did not stain any protein. The GA1-positive population in spleen T cell fraction was not detected in young shrew but most of the T cells were changed to GA1-positive cells in adult shrew. When mixed lymphocyte culture was performed, the GA1-negative spleen T cells in young shrew were changed to express GA1 marker on their cell surface by differentiation. Abbreviations used were as follows: GA1, Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc-Cer; GM1, Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4Glc-Cer; Forssman, GalNAc alpha 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc-Cer.