Effectiveness of the elcatonin transdermal system for the treatment of osteoporosis and the effect of the combination of elcatonin and active vitamin D3 in rat.

The efficacy of percutaneous elcatonin (EC), a hypocalcemic peptide, in the treatment of experimental osteoporosis in rats was evaluated in vivo. Additionally, the effect of the combined use of EC and active vitamin D3 (1,25(OH)2D3) for the treatment was compared with those of three other groups: 1,25(OH)2D3 alone, estradiol plus 1,25(OH)2D3, and a placebo, and low calcium diet (low Ca). The EC transdermal system and the EC plus 1,25(OH)2D3 system, applied to the rat abdominal skin 6 times for 48 h, significantly increased the ash weight and calcium content of the tibia in the rats, compared with those of placebo group (p < 0.05). The EC systems also slightly lowered the alkaline phosphatase activity in plasma of the morbid rats, without a difference in the plasma calcium content. These EC systems were superior to the 1,25(OH)2D3 system and the estradiol plus 1,25(OH)2D3 system in improving osteoporotic parameters. Thus, the EC systems were concluded to be an efficient drug delivery system for Paget's disease and osteoporosis.

[Therapeutic efficacies of suppository of ceftizoxime against experimental infections in mice].

In experimental infections in mice, the therapeutic efficacies of rectal administration of ceftizoxime (CZX) were compared with those of subcutaneous administration. The efficacies of rectal administration were equivalent to those of subcutaneous administration against intraperitoneal infections due to Streptococcus pneumoniae and Escherichia coli. Against Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Morganella morganii and Serratia marcescens, the efficacies of rectal administration were inferior to those of subcutaneous administration. Against urinary tract and respiratory tract infections, the efficacies of rectal administration were slightly inferior to those of subcutaneous administration. Serum concentrations of CZX for rectal administration were less than those of subcutaneous administration.

[Combined action of cephamycin and aminoglycoside antibiotics].

The combined actions of cefoxitin (CFX) with amikacin (AMK), gentamicin (GM) and dibekacin (DKB) were studied against Gram-positive and Gram-negative bacteria. The following results were obtained. The synergistic actions of CFX with AMK, GM and DKB were observed on S. aureus, S. epidermidis, E. coli, S. marcescens, K. pneumoniae, Proteus spp. and Acinetobacter by checker board titration method. The combination of CFX with AMK was most effective. In case of the combination of CFX with AMK, the simultaneous administration showed the highest bactericidal effect, followed by the case of addition of AMK after adding CFX. The phase-contrast microscopic observation on S. marcescens revealed that the bacterial cell prolonged with CFX showed a filament-like form and with AMK almost a normal form. In the combination, lysed cells were observed. The therapeutic experiment of S. marcescens infection in mice demonstrated that the combination of CFX with AMK showed superior effect than that of each drug alone.

[Studies on the combination action of sisomicin, gentamicin and piperacillin, cefmetazole against Pseudomonas aeruginosa and Serratia marcescens].

The combined actions of sisomicin (SISO), gentamicin (GM) and piperacillin (PIPC), cefmetazole (CMZ) against Pseudomonas aeruginosa E-2 and Serratia marcescens T-55 were studied. The following results were obtained. 1. The combinations of SISO-PIPC, SISO-CMZ, GM-PIPC and GM-CMZ using the checker board dilution method on P. aeruginosa E-2 and S. marcescens T-55 were found to have a synergistic effect and the minimum FIC index values were 0.38 in all combinations. 2. With the killing kinetic method, all combinations tested showed a synergistic effect. 3. A synergistic effect of the combinations of SISO-PIPC, SISO-CMZ, GM-PIPC and GM-CMZ was observed in the protective effect on experimental P. aeruginosa E-2 and S. marcescens T-55 infections in mice.

[Bacteriological evaluation of netilmicin].

The following results were obtained from the bacteriological evaluations of netilmicin (NTL), a newly developed antibiotic agent, with gentamicin (GM), dibekacin (DKB) and amikacin (AMK) as the controls. (1) NTL demonstrated broad antibacterial spectra against both Gram-positive and Gram-negative bacteria, but its antibacterial potency against streptococci was not very strong among other Gram-positive bacteria. (2) In terms of distribution of sensitivity of clinically isolated bacterial strains, NTL proved to have antibacterial potency comparable to that of GM and higher potency than that of DKB of AMK against E. coli K. pneumonia, Enterobacter sp., or H. influenzae. However, its efficacy was inferior to GM against Proteus sp., S. marcescens and P. aeruginosa. (3) In conjunction with the influences of pH of culture media or of addition of horse sera upon the antibacterial efficacy, NTL showed an inclination similar to that of GM, DKB and AKM. Its antibacterial efficacy was fortified on the alkaline side or by addition of sera. In connection with the influences of the amounts of inoculated bacteria upon antibacterial efficacy, there were hardly any appreciable influences on it by any of the tested bacterial strains. (4) The interactions of NTL with carbenicillin were evaluated with the chequerboard titration method to find remarkable cooperative actions in any of E. coli, K. pneumoniae, S. marcescens, A. calcoaceticus and P. aeruginosa. (5) The results of evaluation on the patterns of its antibacterial effects revealed that it acted bactericidal in any tested bacterial strains. (6) As to the therapeutic effects against experimental infections in mice, it was found out that NTL = GM greater than DKB and AMK against E. coli, GM greater than NTL = DKB and AMK against K. pneumoniae and GM and DKB greater than NTL greater than or equal to AMK against A. calcoaceticus and P. aeruginosa in the decreasing order of efficacy.