In order to determine whether cyclocytidine (Cyclo-c) captured in liposomes enhanced the effect of a single dose to the same degree as serial doses, the antitumor effect on mouse leukemia L₁₂₁₀ was examined.
Cyclo-c solution (50 mg/ml) was encapsulated in the aqueous phase of neutral liposomes composed of egg lecithine and cholesterol in a 4: 3 moral ratio. The percentage of Cyclo-c taken up in the multilamellar liposomes was from 2.5% to 4.5% and was from 1.6% to 2.5% in the sonicated liposomes.
The liposomally captured Cyclo-c gradually decreased by 50% on day 18 in normal saline solution under room temperature and it decreased by 50% on day 2 in the peritoneal cavities of mice.
With ip administration to CDF₁ female-mice bearing ascitic L₁₂₁₀ cells, the multilamellar liposomes containing normal saline solution did not show any toxicities, antitumor activities and synergistic or antagonistic effects with free Cyclo-c. Sonicated liposomes did not show any toxicities with iv administration.
Antitumor effect in mice bearing 1-day-old ascitic L₁₂₁₀ cells was judged by the percent ILS with ip, sc and iv administration of Cyclo-c or Cyclo-c liposomes. Antitumor effect in the mice bearing L₁₂₁₀ cell colonies in spleen was judged by the suppressive effect in the colony formation with ip administration of Cyclo-c or Cyclo-c liposomes. In the ip-ip experiment, the life prolongation effect of the single Cyclo- c liposome 50 mg/ kg was greater than that of the single Cyclo-c 1, 000 mg/ kg and that of the 5 consecutive doses of Cyclo-c 100 mg/kg/day. In the ip- sc and the ip-iv experiments, enhancement of the antitumor effect of a single dose of Cyclo-c liposome was also observed.
The mean number of spleen colonies in the mice sacrificed 7 days after the iv injection of 1×10⁴ leukemic cells was 61. 6 (range 33-88). The mean number of spleen colonies according to different ip treatments 2 hours after the iv injection of leukemic cells was as follows: 4.7 (0-10) with the single dose of Cyclo-c 500 mg/ kg. 0 with the 5 consecutive doses of Cyclo-c 100 mg/kg/day. 14 (0-18), 2 (0-10) and 0 with the single dose of Cyclo-c liposomes 12.5 mg/kg, 25 mg/kg and 50 mg/kg, respectively.

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Susceptibility to beta-lactam antibiotics of 343 pathogenic strains of Staphylococcus aureus lately isolated from patients in Japan was examined and multiply resistant strains to beta-lactam antibiotics were evaluated concerning with their distribution.
About 80 percent of strains were susceptible to MCIPC, MDIPC, MFIPC and CER. 40 percent to 30 percent of strains were resistant to the third generation cephalosporins and about 30 percent of strains were highly resistant (MIC 100>μg/ ml) to them.
92 percent of 342 strains produced beta- lactamase (penicillinase), but the susceptibility of MCIPC was not remarkably different between beta-lactamase producing and non- producing strains. Therefore, most strains of S. aureus possessed other resistant mechanisms than beta- lactamase against beta-lactam antibiotics. It was supposed that MRSA, isolated lately, possessed new mechanisms of resistance to beta-lactam antibiotics, therefore 62 percent of MRSA (26 strains) were not affected by the temperature of incubation.
Multiply resistant strains to beta-lactam antibiotics distributed throughout Japan and nosocomial infections due to them were not.observed. Therefore almost of all multiply resistant strains were isolated from severe patients, from now in future it is possible that nosocomial infections, caused by them, occur in Japan.

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Antitumor activity of the alkaline soluble fraction of methanol and/ or methane utilizing bacteria was observed on murine tumors. For the purification of active substance from the alkaline soluble fraction of two bacterial strains (Isolate B-46 and Pseudomonas sp. M-27) which showed relatively marked antitumor activity among the 29 strains examined, extraction with chloroform and gel column chromatography were performed, and Fr. III and IV from strain B-46 and Fr. IV from strain M-27 were obtained.
These substances were water soluble and amphoteric, consisting mainly of sugar and amino acid. The substances did not show direct cytotoxic activity on mammalian cells in vitro, but showed marked antitumor activity on the Incites form of sarcoma 180 and IMC carcinoma, and slight activity on B-16 melanoma in vivo. Furthermore, growth inhibitory activity was observed on the solid form of IMC carcinoma and MM 46 mammary carcinoma grown subcutaneously.
Cytotoxic activity (cytostasis and cytolysis) of adherent cells in peritoneal exudate cells from mice treated with i. p. injections of B-46 Fr. III, IV or M-27 Fr. IV was determined in vitro using EL-4 mouse leukemic cells as target cells. The enhancement of cytotoxic activity of adherent cells was observed by means of the uptake of ³H-thymidine into DNA of target cells or the release of radioactivity from ³H-uridine-labeled EL-4 cells.
When mice were given these substances i. v., the maximum titer of interferon was observed in the serum 6 hours after the injection. These results suggested that B-46 Fr. III, IV and M-27 Fr. IV isolated from methanol utilizing bacteria induce tumor regression by specific and/ or non-specific enhancement of the host defence mechanism of tumor bearing mice.

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We have presented a case of Candida albicans septicemia which was cured with an antifungal imidazole derivative, miconazole, together with a few discussions.
In this case, a 32-year-old man was operated on by rectectomy for colonic polyp. While he was under management by IVH, a high fever appeared, with C. albicans isolated from the venous blood, arterial blood and myelic blood. He was then treated with 800 to 1, 200mg daily of miconazole, every day, for 33 days (to a total dose of 30.2g), ran a favorable course, and was eventually' discharged. The treatment was associated with no side effects of the drug. The MICs of miconazole for the isolates were in the range from 0.39 to 0.78 μg/ml, and the blood level of the drug reached a peak of 0.90 μ g/ml following the administration of 400mg of the drug.
We also compared the antibacterial activities of amphotericin B (AMPH), miconazole and 5-fluorocytosine (5-FC) against the 29 recent isolates of C. albicans from clinical materials. The antibacterial activity of AMPH was comparable to that of miconazole, with their MICs for the isolates distributed in the range of not more than 1.56 μ g/ml. The antibacterial activity of 5-FC was not as potent as those of the former.
Because miconazole has proved to have a potent antibacterial activity, accompanied by a low incidence of side effects, we think that this drug will be a useful therapeutic agent for deep candidiasis.

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A double blind group comparison study was performed to ascertain the efficacy and safety of cefoperasone (CPZ) as compared with cefotiam (CTM).
The following results were obtained:
1. Efficacy: The clinical efficacy rate in postoperative superficial purulent infections (Trial A), were 95.1%(58/61) and 80.8%(42/52) for the CPZ group and CTM groups, respectively. The efficacy rates in postoperative peritonitis and/ or dead space infections (Trial B) were 84.7%(50/59) and 53.7%(29/54) for the CPZ and CTM groups, respectively; the CPZ group showed a significantly better results in both trials.
2. Overall improvement: The overall improvement rates at the end of Trial A were 88.9%and10.8% for the CPZ and CTM groups, respectively; in Trial B they were 81.4% and 57.4% for the CPZ and CTM groups, respectively. In Trial B, CPZ group showed a significantly better result than the CTM group.
3. Usefulness: In Trial A, usefulness rates as judged by the surgeons were 80.6% and 63.5% for the CPZ and CTM groups, respectively; in Trial B, the usefulness rates were 71.9% and 38.5% for the CPZ and CTM groups, respectively. In Trial B, the CPZ group showed a significantly better result than the CTM group.
4. Bacteriology: In Trial A, the eradication rates of clinical isolates were 78.4% and 55.6% for the CPZ and CTM groups, respectively; in Trial B, the eradication rates were 60.7% and 37.5% for the CPZ and CTM groups, respectively.
5. Side effects: Side effects were noted in 4 cases (2.9%) in the CPZ group and 5 cases (3.9%) in the CTM group. Abnormal labolatory findings were noted in 8 cases treated with CPZ group and 11 cases treated with CTM group. Significant differences were, however, not observed between the two groups, either in kind or frequency of side effect, or in details or frequency of abnormal laboratory findings.
As shown above, CPZ demonstrates superior clinical efficacy and equal safety in comparison with CTM. Based on this we conclude that CPZ is a highly useful antibiotic for the treatment of postoperative infections.

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