Rinzo Soejima

Hydrocortisone inhibits the respiratory burst oxidase from human neutrophils in whole-cell and cell-free systems

The effects of hydrocortisone on the respiratory burst oxidase (NADPH oxidase, EC 1.6.99.6) from human neutrophils in both whole-cell and full soluble (cell-free) systems were investigated. In the whole-cell system, hydrocortisone inhibited the generation of superoxide by neutrophils exposed to phorbol myristate acetate, suggesting that steroids inhibit the bactericidal capacity of the body in an acute inflammatory phase. Hydrocortisone, which was added to the cuvette after the addition of NADPH and before the addition of sodium dodecyl sulfate, in a cell-free system, was found to inhibit the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate. The concentration of hydrocortisone required for 50% inhibition of oxidase was 40 microM. Its inhibition was dose- and time-dependent in the cell-free system. However, hydrocortisone did not alter the Km of the oxidase for NADPH. These results suggest that steroids inhibit the reconstitution of NADPH oxidase by sodium dodecyl sulfate in the cell-free system, and that they do not alter the affinity to NADPH of the oxidase.

In vitro and in vivo antichlamydial activities of newly developed quinolone antimicrobial agents.

The in vitro and in vivo activities of three newly developed quinolone antimicrobial agents (sparfloxacin, tosufloxacin, and OPC-17116) were investigated. All three agents showed potent in vitro activities against Chlamydia psittaci, C. trachomatis, and C. pneumoniae with MICs that ranged from 0.031 to 0.125 micrograms/ml. These values were higher than those of minocycline (0.0075 to 0.015 micrograms/ml) but lower than those of erythromycin (0.25 to 0.5 micrograms/ml) and ofloxacin and ciprofloxacin (0.5 to 1.0 micrograms/ml). Mice were challenged with 10(5) inclusion-forming units of C. psittaci each by nasal instillation. All untreated control animals died within 7 days. The survival rates of mice treated with 40 mg of sparfloxacin, OPC-17116, or tosufloxacin per kg of body weight every 12 h for 7 days were 73, 73, and 60%, respectively, 7 days after the challenge. The survival rate of mice treated with ofloxacin at the same dosage was 53%. On the basis of the above results, we concluded that these three new quinolones might be useful in the treatment of chlamydial respiratory infections.

Assay of Specific Anti-Chlamydia pneumoniae Antibodies by ELISA Method

We measured anti-Chlamydia pneumoniae (C. pneumoniae) specific antibody titers by means of a newly-developed enzyme-linked immunosorbent assay (ELISA) method using an anti-C. pneumoniae specific antibody detection reagent. The clinical usefulness of this method was hereby evaluated. The IgG, IgA and IgM titers in 418 serum specimens obtained from patients with respiratory tract infections were measured by this new ELISA method, and the results were compared with the titers determined for the same specimens with the micro immunofluorescence (Micro-IF) method. The results showed good correlation coefficients for IgG, IgA and IgM. The two assay methods showed high agreement rates for positivity and for negativity. Specimens which did not yield the same results with the ELISA method and the Micro-IF method were subjected to analysis by the Western blot method, and the rates of agreement with the ELISA results were high. In addition, the child (0 approximately 15 yrs old; n = 122) and adult (16 approximately 90 yrs old; n = 133) cases were classified on the basis of being antigen-positive or antigen-negative at the initial examination, and their antibody-positive rates were determined. The adults showed no statistically significant differences in the antibody-positive rates for either IgG or IgA antibodies as a function of the pretreatment antigen status. However, the children showed statistically significant (p < 0.001) differences in the antibody-positive rates for both IgG and IgA antibodies as a function of the antigen status in the antigen-positive group compared with the rates in the antigen-negative group. Furthermore, the IgM-positive rates for the children were high in the antigen-positive group compared with the rates in the antigen-negative group, and the difference was statistically significant (p < 0.001). The IgM-positive rates in the adults were also significantly (p < 0.05) different between the antigen-positive group and the antigen-negative group. The Micro-IF method was applied to 34 specimens from antigen-positive patients, and 22 specimens were found to show an IgG titer of > or = 512 or an IgM titer of > or = 16. The diagnoses of these patients were acute respiratory disease in sixteen, pneumonia in four. Application of the ELISA-method to those 22 specimens showed all of them to exhibit IgG absorbance of > or = 0.6 and IgA absorbance of 0.2. The results described above indicate the clinical usefulness of our new ELISA method for the detection of antibodies specific for C. pneumoniae. The significance of this ELISA method for serological diagnosis of C. pneumoniae infections and the criteria for diagnosis of acute infections were also discussed.

Supplemental Fosfomycin and/or Steroids that Reduce Cisplatin-Induced Nephrotoxicity

The protective effects of fos-fomycin and steroids on the nephrotoxicity induced by cisplatin in lung cancer patients were studied by measuring N-acetyl-β-D-glucosaminidase (NAG) activity in 24-hour urine, creatinine clearance, serum creatinine and blood urea nitrogen as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental fosfomycin or steroids, the 24-hour urine NAG level increased two-fold (15.5 ± 7.5, p < 0.01) over the pretreatment level (8.0 ± 5.2) 3 days after anticancer therapy. Supplemental fosfomycin or steroids inhibited an increase in urinary NAG level 3 days after the anticancer therapy. There were, however, no significant changes in creatinine clearance, serum creatinine and blood urea nitrogen levels before and after anticancer and/or supplemental therapies. These results suggest the possibility that supplemental treatment with fosfomycin, like that with steroids, reduces cisplatin-induced nephrotoxicity, especially proximal tubular damage.

In vitro and in vivo activities of azithromycin, a new azalide antibiotic, against Chlamydia

The in vitro and in vivo activities of azithromycin against chlamydia were investigated. The MIC of azithromycin for five standard strains of different species of chlamydia and six wild-type strains of Chlamydia pneumoniae was 0.125 microgram/ml, which was superior to that of erythromycin but inferior to those of clarithromycin and minocycline. However, the therapeutic effect of a 7-day course of azithromycin at a dose of 10 mg/kg of body weight administered orally once daily to mice with experimental Chlamydia psittaci pneumonia was excellent, with a 100% survival rate at 14 days after infection, which was the same as that for treatment with minocycline administered at 10 mg/kg twice daily; all erythromycin treated animals died within 10 days. When treatment was discontinued 3 days after the infection, the survival rate for mice treated with azithromycin was 90% and that for mice administered minocycline was 30%. These results suggest that azithromycin may be useful in the treatment of respiratory infections caused by intracellular pathogens, including chlamydia because of its excellent accumulation within host cells.

Characterization of a Chlamydia pneumoniae Strain Isolated from a 57-Year-Old Man

The isolation of Chlamydia pneumoniae, especially from elderly persons, is generally not easy. Recently, we succeeded in isolating a chlamydial strain, which was designated KKpn‐15, from a 57‐year‐old man suffering from acute bronchitis. It was compared with well established strains of C. pneumoniae, C. trachomatis and C. psittaci, and its biological properties, such as the morphology of elementary bodies (EBs) and inclusions, and the immunochemistry of EB proteins, were investigated. Based on the results obtained in the present study, it was confirmed that the new chlamydial strain, KKpn‐15, is a member of the C. pneumoniae strain and that the organisms of KKpn‐15 are useful as an antigen for the serodiagnosis and epidemiology of C. pneumoniae infection.

Ofloxacin in respiratory tract infection. A review of the results of clinical trials in Japan.

SummaryAn open clinical study of ofloxacin in respiratory tract infections was conducted with patients receiving daily doses of ofloxacin 300mg, 400mg or 600mg. The duration of treatment was 6 to 14 days for 70% of the patients. Ofloxacin was effective in 668 of 828 patients analysed (80.7%). Of 293 patients with upper respiratory infections, the efficacy rate was 85.3%. In 535 cases with lower respiratory infections, ofloxacin was effective in 78.1%. It is noteworthy that a 70% efficacy rate was obtained in 80 cases with intractable chronic diffuse panbronchiolitis primarily associated with Pseudomonas aeruginosa. There was no difference in the efficacy rate among various daily doses or severity of infections. In lower respiratory infections the bacterial eradication rate was 80.9% for Gram-positive aerobes (including 80% for Staphylococcus aureus and 76.5% for Streptococcus pneumoniae) and 72.1% for Gram-negative aerobes (including 92.6% for Klebsiella pneumoniae, 32.3% for P. aeruginosa and 97.1% for Haemophilus influenzae). Although there were no serious cases, adverse reactions were noted in 46 of 843 patients (5.5%): 38 cases (4.5%) of gastrointestinal tract reactions (nausea, vomiting, heartburn, etc.), 4 cases (0.5%) of hypersensitivity (e.g. eruption) and 19 (2.3%) of central nervous system effects (e.g. dizziness). Abnormal changes in laboratory findings included elevations of AST (1.2%) and ALT (1.5%) and an increase in the eosinophil count (1.7%).

Urinastatin (Kunitz-Type Proteinase Inhibitor) Reducing Cisplatin Nephrotoxicity

The authors investigated the reductive effects of a Kunitz-type proteinase inhibitor, urinastatin, on the nephrotoxicity seen in lung cancer patients treated with cisplatin by measuring N-acetyl-beta-D-glucosaminidase (NAG) activity and beta 2-microglobulin (BMG) content in 24 hour urine, creatinine clearance, blood urea nitrogen (BUN), serum creatinine, uric acid, and BMG as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental urinastatin, the 24 hour urine NAG and BMG levels increased more than three-fold over the pretreatment levels, 3 days after anticancer therapy, respectively. Creatinine clearance significantly decreased and levels of BUN, serum uric acid, and BMG in control patients significantly increased over the corresponding pretreatment levels, 3 days after anticancer therapy. However, supplemental urinastatin reduced abnormalities in levels of all these factors 3 days after therapy. These results suggest that supplemental urinastatin protects from cisplatin-induced nephrotoxicity, especially proximal tubular damage.

Elastase/Antielastase Systems in Pulmonary Diseases

ABSTRACT: Levels of serum elastase 1 in a variety of respiratory diseases were studied. In patients with pulmonary emphysema, pulmonary fibrosis, bronchial asthma, or pulmonary infections, including pneumonia and pulmonary tuberculosis, serum elastase 1 levels were greater than those of an age-matched control group. In lung cancer patients, however, the serum elastase 1 level was within normal limits. Although α1-antitrypsin levels were significantly higher in patients with pulmonary infections and lung cancer than in the normal group, they were within normal limits in patients with pulmonary emphysema, pulmonary fibrosis, and bronchial asthma. Alpha2-macroglobulin levels were slightly increased in patients with pulmonary emphysema and pneumonia. These results suggest that the increases in serum elastase 1 levels in these respiratory diseases may be mainly caused by an imbalance of elastase/antielastase system in the lung tissue and the bloodstream.

A Randomized Controlled Postoperative Adjuvant Chemotherapy. Trial of CDDP+VDS+UFT and UFT alone in Comparison with Operation Only for Non-Small Cell Lung Carcinomas. Second Study.

本 稿 で は,病 期 別,組 織 型 別 の 解 析 結 果 を示 し た.そ の 結 果,病 期 別 で はIIIA期 に お い て A群25.0%,B群38.1%,C群16.7%,組 織 型 別 で は 腺 癌 に お い てA群64.9%,B群67.9%, C群43.2%と,補 助 化 学 療 法 群(特 にUFT単 独 投 与)の 生 存 率 が 良 好 で あ っ た. これ らの 結 果 よ り,手 術 後 補 助 化 学 療 法 と し て のUFT単 独 効 果 に つ い て 今 後 病 期 別 あ る い は 組 織 型 別 に デ ザ イ ン さ れ た 研 究 の 必 要 性 が 示 唆 され た. 〔肺 癌 36 (7): 863~871, 1996〕