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Biomedical subjects

Jingoro Shimada

Publications and source records attributed to Jingoro Shimada.

11 recordsLinked to original sources

Alarming trend of clarithromycin-resistant Streptococcus pyogenes in Japan (1998-2002).

We investigated annual changes in clarithromycin resistance and resistance genes in 579 strains of Streptococcus pyogenes isolated from patients with symptomatic respiratory tract infections who visited primary medical institutions during the 5-year period from 1998 to 2002. The minimum inhibitory concentrations (MICs) of clarithromycin for S. pyogenes were measured using the standard broth microdilution method according to the National Committee for Clinical Laboratory Standards (NCCLS) guidelines, and strains showing MICs of 1 microg/ml or greater were regarded as being resistant to clarithromycin, according to the resistance standard specified by the NCCLS. The rates of S. pyogenes resistance to clarithromycin were 7.3% overall, 5.8% in 1998, 4.9% in 1999, 7.7% in 2000, 6.4% in 2001, and 11.1% in 2002. While the annual rates fluctuated slightly each year, an overall tendency to increase was observed during the 5-year period. Regarding the macrolide-resistance genes in the macrolide-resistant strains, mefA/E (+)/ ermB(-) was the most common genotype detected in these strains, while the ermB (+)/ mefA/E (-) and mef A/E (-)/ ermB (-) genotypes were detected at about the same rate. The MICs of clarithromycin for the ermB (+) strains tended to be higher than those of the mefA/E (+) strains, but some mefA/E (-) / ermB (-) strains also exhibited high MICs of clarithromycin, similar to those of the ermB (+) strains. The above results indicate that the number of clarithromycin-resistant strains of S. pyogenes is gradually increasing and that the resistance is becoming stronger; thus, special attention must be paid to the appearance of macrolide-resistant strains of S. pyogenes.

Anti-Bacterial Agents↗

The antibacterial effects of terpene alcohols on Staphylococcus aureus and their mode of action.

The study was made of the antibacterial effects of three terpene alcohols on Staphylococcus aureus, focusing on the leakage of K+ ions and toxicity over time. The leakage of K+ ions was monitored continuously with a K+-electrode. Our results suggested that the terpene alcohols, namely, farnesol, nerolidol and plaunotol might act on cell membranes. The rank order of effectiveness, farnesol>nerolidol>plaunotol, was the same in the toxicity assay and in the examination of the leakage of K+ ions, when we considered the initial rate and the amount of leaked K+ ions. The rank order agreed with the results of a growth-inhibition assay reported previously. The antibacterial activity reflected the initial rate of leakage of K+ ions, suggesting that damage to cell membranes might be one of the major modes of action of these terpene alcohols. The results also demonstrated that the initial rate of leakage and the amount of leaked K+ ions are useful as indices of the antibacterial activities of hydrophobic compounds.

Anti-Bacterial Agents↗

[Serotypes and antibody levels of group B streptococci in pregnant women].

Group B streptococcus were isolated from 1404 pregnant out-patient women in the Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, from June 1, 1992 to May 31, 2001. Serotype of 187 (13.3%) fresh isolates of GBS was determined by using hemolytic streptococcus-typing immune sera (Denka Seiken, Tokyo, Japan). With these strains there were 59 (31.6%), 46 (26.6%), 19 (10.2%), 16 (8.6%), 16 (8.6%), 12 (6.4%) and 3 (1.6%) indicating that their types were VIII, VI, III, Ia, V, Ib and II respectively. Also, bacterial agglutination reaction was employed for detection of titer to GBS in pregnant women serum. Positive reaction showed in 31 (57.4%) samples but 23 (42.6%) samples were not seen in this essay. It is assumed that the high antibody levels in pregnant women serum plays an important role as an in vivo defence factor in neonatal infection by GBS.

Antibodies, Bacterial↗

In vitro activity of S-3578, a new broad-spectrum cephalosporin active against methicillin-resistant staphylococci.

The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated. The MICs of the drug at which 90% of the isolates were inhibited were 4 micro g/ml for methicillin-resistant Staphylococcus aureus (MRSA) and 2 micro g/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively. The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.5 micro g/ml). In time-kill studies with 10 strains each of MRSA and methicillin-susceptible S. aureus, S-3578 caused more than a 4-log(10) decrease of viable cells on the average at twice the MIC after 24 h of exposure, indicating that it had potent bactericidal activity. Furthermore, in population analysis of MRSA strains with heterogeneous or homogeneous resistance to imipenem, no colonies emerged from about 10(9) cells on agar plates containing twice the MIC of S-3578, suggesting the low frequency of emergence of S-3578-resistant strains from MRSA. S-3578 was also highly active against penicillin-resistant Streptococcus pneumoniae (PRSP), with a MIC(90) of 1 micro g/ml, which was comparable to that of ceftriaxone. S-3578 also had antibacterial activity against a variety of gram-negative bacteria including Pseudomonas aeruginosa, though its activity was not superior to that of cefepime. In conclusion, S-3578 exhibited a broad antibacterial spectrum and, particularly, had excellent activity against gram-positive bacteria including methicillin-resistant staphylococci and PRSP. Thus, S-3578 was considered to be worthy of further evaluation.

Bacterial Proteins↗

In vivo antibacterial activity of S-3578, a new broad-spectrum cephalosporin: methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa experimental infection models.

The in vivo antibacterial activity of S-3578, a new parental cephalosporin, was compared with those of cefepime, ceftriaxone, ceftazidime, imipenem-cilastatin, and vancomycin. The efficacy of S-3578 against systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) SR3637 (50% effective dose [ED(50)], 7.21 mg/kg of body weight) was almost the same as that of vancomycin. In contrast, cefepime and imipenem-cilastatin were less active against this pathogen (ED(50)s, >100 and >100 mg/kg, respectively). S-3578 was the most effective compound against penicillin-resistant Streptococcus pneumoniae SR20946 (ED(50), 1.98 mg/kg). S-3578 (10 mg/kg) induced a significant reduction in the numbers of viable MRSA SR17764 and Pseudomonas aeruginosa SR10396 organisms in polymicrobial pulmonary infections. The therapeutic efficacy of S-3578 was more potent than that of the combination of vancomycin and ceftazidime. High levels of S-3578 were detected in plasma in vivo, and its efficacy against experimentally induced infections in mice caused by MRSA and P. aeruginosa reflected its potent in vitro activity. We conclude that S-3578 is a promising new cephalosporin for the treatment of infections caused by gram-positive and -negative bacteria, including MRSA and P. aeruginosa.

Abscess↗

Drug delivery system to control infectious diseases.

Viral replication takes place only in the host cell. From this intrinsic characteristics of virus, therapeutics agents specifically target to the virus genome is quite difficult. However, genetic medicine toward viral gene is promising in terms of selective toxicity for viral infection. Genetic medicine including antisense DNA, ribozyme, aptamer, triplex and gene itself has been enthusiastically studied in the past decades. At the early age of genetic medicine research, there were many skepticisms about clinicla usage. However, the first antisense DNA is on the market in the USA and Europe. Although the mechanism of antisense manner is still controversial, it was clearly epoch-making in the human application of genetic medicine. Genetic medicine opens the possibility to combat virus replication in a sequence specific way. Virus utilizes the specific receptor on the host cells for entry; this is the reason why virus has organ specificity (tropism). Since life cycle of each virus is unveiled, target for the therapeutic agent's reveals in a molecular level. Furthermore, decipher of viral genome has been carried out rapidly and inexpensively. Once we hand entire sequences of viral genome, more theoretical way to design genetic medicine targeted viral infection could be main stream in the development of antiviral agents. Furthermore, efficient drug delivery system (DDS) to deliver antiviral agents to the infectious site is highly needed. In this article, we will address the target molecule of antiviral agents and possible DDS for the infectious disease.

Animals↗