CHEMOTHERAPY
Online ISSN : 1884-5894
Print ISSN : 0009-3165
ISSN-L : 0009-3165
Volume 18, Issue 2
Displaying 1-10 of 10 articles from this issue
  • KAZUO IWATA, TATSUO NAGAI, YURIKO NOZU, SAEKO HIDAKA
    1970 Volume 18 Issue 2 Pages 129-132
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    In an attempt to check a possibility of absorption of amphotericin B from the skin tissue and the consequent induction of chronic toxicity when applied topically for a long period to laboratory animals, the antibiotic content in the blood and various organs were determined by a microbiological assay method devised by the authors which had been described in the preceding paper.
    A micropulverized preparation of the antibiotic suspended in olive oil was administered onto the well-shaved skin in the back of rabbits with a dimension of ca. 5 cm × 5 cm. The suspension was given at the rate of 6 mg and 60 mg, respectively, every 24 hours for 4 weeks to each rabbit of the two groups consisting of five males each. Blood was collected every one week, and organs (liver, spleen and kidneys) were taken out immediately after the final collection of blood. These materials were applied to determination of amphotericin B content by a turbidity method using a strain of Candida albicans; the lower limit in an established determination standard curve was 0.003mcg/ml. The results obtained are as follows.
    All the animals of the both groups were found to be below the lower limit of the antibiotic content in all the blood and three organs. During the whole period of observation, all were healthy, showing a normal increase in body weight. Neither any general and local symptoms nor any macroscopic pathological changes in all the organs including the above three were noticed.
    These results present an evidence that, even when continuously given topically for a long term in a relatively large dose, amphotericin B cannot penetrate through the healthy skin tissue to distribute into the blood stream and organs in demonstrable amounts at least, and, in consequence, does not exhibit any serious general and local side effects. Thus, a possibility that this antibiotic might induce chronic toxicity would be denied in case of topical use at least.
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  • YUTAKA KANAZAWA, TOSHIO KURAMATA, ISAMU MARUYAMA, KIROKU NAKAJIMA
    1970 Volume 18 Issue 2 Pages 133-139
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    A new synthetic penicillin, carbenicillin was studied bacteriologically and clinically. The results obtained were summarized as follows :
    1) In a study by the agar plate dilution method on a total of 96 strains of 20 bacterial species, β-hemolytic Streptococci, penicillinase non-producing Staphylococci and Pneumococci were found to be very susceptible to the agent with the MICs of 0.38μg/ml or less. Enterococci, α-hemolytic Streptococci, penicillinase producing Staphylococci, Escherichia, Salmonella, Shigella, Pseudomonas and Proteus-Providence were fairly susceptible with the MICs ranging 50-0.38 pg/ml, while Klebsiella displayed a rather poor susceptibility with the MICs over 100μg/ml.
    2) By the thin-layer cylinder-plate method using B. subtilis PCI 219 as a test organism, carbenicillin levels in body fluids were assayable to the lower limit of 0.1 pg/ml. Following a single intramuscular injection of 1, 000 mg of the agent, the blood peak levels were obtained on the lapse of 30 minutes to one hour, with a persistence of effective serum levels over ensuing 6 hours. Bile levels were higher than its blood levels. And the agent was excreted in urine in high concentration and recovered mostly from urine.
    3) In order to apply the single-disc method to the sensitivity test of carbenicillin in clinical laboratory, statistical analysis of the dose-response data concerning interrelationship between MIC and diameter of inhibition zone was conducted.
    4) Carbenicillin treatment was effective in 3 cases with urinary tract infections caused by Proteus or E. coli.
    5) In a case of systemic lupus erythematosus with hypersensitivity to aminobenzyl-penicillin, skin-redness was observed in the region of injection. No side-effect was noticed in other cases of treatment.
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  • With Special Reference to the Combination of Acetyl-Spiramycin with Chloramphenicol or Tetracycline
    OSAMU KITAMOTO, KAZUFUTO FUKAYA
    1970 Volume 18 Issue 2 Pages 140-144
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    The synergistic or antagonistic actions between acetyl-spiramycin (AC-SPM) and chloramphenicol (CP) or tetracycline (TC) were investigated in vitro in respect of combined use of antibiotics and small clinical trials were performed. The results obtained were as follows.
    1. The drug susceptibility test of Staphylococcus aureus strains carried out by agar dilution plate method showed synergistic action in about a half of 42 strains tested. In case of gram-negative bacilli, one antibiotic had no influence upon another, and vice versa. These facts were similarly observed on both combinations of AC-SPM with CP or TC.
    2. The effect of such antibiotic combination upon growth curve of two strains of Staphylococcus aureus in broth was not so obvious comparing with the action of each single antibiotic.
    3. Four cases were treated with the combination of AC-SPM and CP, being administered with tablet containing 125 mg of each drug. Eight tablets were administered orally in 4 divided doses for 5 days and all of them showed good effectiveness.
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  • OSAMU KITAMOTO, KAZUFUTO FUKAYA, O. KITAMOTO
    1970 Volume 18 Issue 2 Pages 145-152
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    On a new cephalosporin derivative, cephalexin (CEX), experimental and clinical studies were performed being compared with cephaloridine (CER) and cephalothin (CET). The results obtained were as, follows.
    1. The sensitivity of CEX against Staphylococcus aureus was slightly lower than other two cephalosporins. On the medium of pH 6.5 MIC values were smaller than on that of pH 7.2. In the case of Gram negative bacilli there was little difference of MIC value among three cephalosporins, but pH of medium gave the same influence on MIC in three drugs.
    2. Effects of lysozyme added to CEX were examined on growth curve of several strains of Staphylococcus aureus and results of such treatment to experimental infection in mice were compared with control group, resulting occasionally favorable effects with lysozyme in both instances.
    3. In the experimental subcutaneous staphylococcal infection in mice, effects of CEX oral administration for inhibiting abscess formation were compared with CER intramuscular injection, showing comparable results in both groups.
    4. The bile level following oral administration to dog reached as high as five times of serum level, and moreover urinary levels rose to twenty to thirty times of it.
    5. In the measurement of tissue distribution after oral administration to mice, very high level was obtained only in the kidney, while in other tissues the concentrations were lower than that of serum.
    6. Daily urinary excretion rates were high in the serial dosing to human subjects, but fecal concentration was relatively low in general.
    7. In summary of clinicla results, each of all four cases with pyelitis and colitis showed good response, further to one case of angina and three of four respiratory tract infections CEX was also effective. However in one patient with aubacute bacterial endocarditis clinical symptoms were persistent, although the number of Streptococci isolated from blood had been reduced gradually. Any side reaction was not observed except one case which complained of anorexia and epigastric fullness.
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  • HAJIME HASHIMOTO, TETSUO SAWAI, KEN WATANABE
    1970 Volume 18 Issue 2 Pages 153-156
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    Antibacterial spectrum of cephalexin is similar to that of cephaloglycin. They are effective to both gram negative and positive bacteria except the strains of Pseudomonas, E. freundii and some of Proteus. species. Antibacterial activity of the drug to the strains of E. coli or Staphylococci which are either moderately resistant or sensitive to penicillin G, did not show any significant changes on the media at various pH. But in the Staphylococcal strains, highly resistant to penicillin G, the decrease of pH of the assay media caused the increase in antibacterial activity of the drug. This increase was seen only when Difco agar plate was used. When inoculum size was decreased to one hundredth, the level of drug resistance in most strains decreased to about one half. Prolongation of incubation time did not affect significantly the level of resistance except cephalexin resistant strains.
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  • With Special Reference on the Behaviour of Microorganism Adapted to Bile Salts under the Presence of Antimicrobial Agents
    YOSHITAKA MATSUMOTO
    1970 Volume 18 Issue 2 Pages 157-166
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    1) The ability of E. coli (NIHJ) to grow in bile salt containing media was studied. E. coli was adapted by serial transfer in cholate and deoxycholate containing media to grow more rapidly than unadapted cultures.
    2) No changes of biochemical nature of E. coli adapted by 7 times transfer in 1% cholate and 1% deoxycholate were shown comparing with unadapted E. coli.
    3) In study of antibiotic susceptibility of unadapted, adapted and reversed E. coli, these 3 microorganisms showed the same values of minimal inhibitory concentration to cephaloridine (CER), kanamycin (KM), ampicillin (AB-PC) and chloramphenicol (CP).
    4) Antibiotic susceptibility to CER, cephaloglycin (CEG), KM, deoxykanamycin, CP and AB-PC was studied in 25 strains of E. coli isolated from the patients with urinary tract infection and 14 strain, isolated from those with biliary tract infection. The patterns of susceptibility between these 2 groups of E. coli were different except CEG and CP. These differences were statistically significant (P<0.01-0.05).
    5) Between adapted and unadapted E. coli, a marked difference in viable numbers in media with several antibiotics was demonstrated. The adapted E. coli grown in media containing CER, AB-PC or KM decreased more rapidly after 5 hours than the unadapted E. coli.
    6) In 5 hours' culture in media containing CER and AB-PC, the decrease in viable counts of E. coli isolated from feces of the patients with the urinary tract infection was often found to be more significant than E. coli in urine from the same patients.
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  • Especially on the Threshold Shift of the Pinna Reflex and Histopathological as well as Histochemical Findings of the Inner Ear
    MASATOYO AKIYOSHI, KIICHI SATO, KAZUO HAYANO, MUNETOSHI YOSHIZAWA
    1970 Volume 18 Issue 2 Pages 167-183
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    The ototoxicity of tuberactinomycin (TUM) was examined by using the audiometer for the guinea pig and histopathologically as well as histochemically on 148 guinea pigs (300g) and compared with the ototoxicity of kanamycin (KM) as well as viomycin (VM). These antibiotics were injected at the various daily doses ; 80mg/kg subcutaneously for 35 days, 100mg/kg, 200mg/kg and 400mg/kg intramuscularly for 28 days, respectively. The incidence of hearing impairment and histological damage was the highest at the daily dose of 400mg/kg; severe hearing impairment associated with extensive loss of the outer hair cells did not occur in the 25 TUM treated animals, but in 4 of the 10 KM treated animals and in 100% of the 10 VM treated ones. No remarkable decrease in succinic dehydrogenase activity of the hair cells of the organ of Corti was found in the TUM treated animals. There was no distinct impairment in equilibrium in the TUM treated animals. It may be concluded that TUM has a mild ototoxicity but its ototoxic effect is much weaker than VM and KM.
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  • Effect of TC-17 on Tumor Cells
    CHIHARU SAITO
    1970 Volume 18 Issue 2 Pages 184-188
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
    Direct action of a potential anti-tumor agents, TC-17 on tumor cells was investigated.
    1. The compound showed a marked damaging activity on ascites tumor cells and inhibition of nucleic acids synthesis in HeLa cells with a concentration of 0.05%.
    2. The cytolytic activity on tumor cells was more strong and selective than the hemolytic activity on rabbit RBC.
    3. Inhibitory activities on the respirations and anaerobic glycolysis of EHRLICH ascites tumor cells. were very weak even at the high concentration of 5×10-3 M (0.59%).
    4. The tumor cell damaging activity of the compound was very insufficient in regard to cytocidal activity.
    5. Fluorescent staining of tumor cells with TC17 showed that the compound had a strong affinity for intra and extra nuclear nucleoproteins.
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  • TOSHIO KOIKE
    1970 Volume 18 Issue 2 Pages 189-205
    Published: March 25, 1970
    Released on J-STAGE: August 17, 2011
    JOURNAL FREE ACCESS
    In 1861 BENTLEY reported the effectiveness of podophyllin on skin cancer, and in 1942 KAPLAN used this substance on condyloma acuminata and also ascertained its effectiveness. The mechanism of its action was attributed by SULLIVAN et al. in 1947 to the impediment of the mitosis of the cells in its metaphase.
    In the present studies, the antitumor agent ethyl hydrazide of podophillic acid (SP-I) was administered to the animals with such experimental tumors as YOSHIDA's sarcoma, EHRLICH's ascites carcinoma and sarcoma-180. and the antitumor effect of the substance in vitro and in vivo was explored together with a study on the clinical application of SP-I. The results obtained were as follows :
    1. In the experiments in vitro, the antitumor effectof SP-1 on YOSHIDA's sarcoma was recognized at a concentration of 0.00125mcg/ml and above, and its inhibitory effect on the growth of the cells reached 50% at a concentration of 0.05 mcg/ml. Its anti-tumor effect on EHRLICH's ascites carcinoma was not remarkable so as to allow the survival of the animal until its concentration reached 12.5mcg/ml and above. The survival of the animal was most effected by keeping SP-I in contact with the tumor at 37°C for 12 hours.
    2. In the experiments in vivo, SP-I had little life prolonging effect against a sarcoma-180 of the ascites type. As to the tumors of a solid type, it was noted that the increase of the tumor weight was inhibited up to 55.4% in the case of EIIRLICH's solid ascites carcinoma and 70.6%in the case of solid sarcoma-180 at a dose level of 50mg/kg body weight.
    3. As to the morphological changes suffered by the cells, inhibition of karyokinesis was observed at SP-I concentrations between 50mg/ml and 0.8mcg/ml.
    4. SP-I has been clinically applied to a total of 37 cases of cancers of the stomach, esophagus, liver etc. over five years and objective improvement was attained in 14 cases of postoperative cancer recurrence and 2 cases still under administration.
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  • 1970 Volume 18 Issue 2 Pages 206-246
    Published: March 25, 1970
    Released on J-STAGE: March 08, 2011
    JOURNAL FREE ACCESS
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