Increase in alkaline phosphatase activity in the liver of mice bearing Ehrlich ascites tumor.

In mice bearing Ehrilich ascites tumors, alkaline phosphatase activity was increased fivefold in the liver and by 50% in the kidney. In mice bearing solid tumors caused by inoculation of tumor cells into the axillary region, the activity of this enzyme in the liver was increased 11-fold, whereas the activity in the kidney did not change. Alkaline phosphatase activities in the liver and kidney were not altered by administration of adrenal steroids. Adrenalectomy, fasting, and pregnancy did not affect the activity of alkaline phosphatase in the liver and kidney. Treatment with tumor extracts or ascites fluid of normal mice increased liver alkaline phosphatase activity. These findings suggested that the elevation of liver alkaline phosphatase activity was cuased primarily by the tumor itself, and not by hormonal imbalance provoked secondarily by the presence of the tumor.     

Clinical studies of intrarectal administration of 5-FU emulsion as an adjunct to surgical treatment for rectal cancer

Preoperative intrarectal administration of 5-FU emulsion was attempted as an adjuvant chemotherapy to surgery for rectal cancer. The drug concentrations of resected specimens were determined and histological examinations of them were carried out in order to evaluate the effect of anticancer drugs on the metastatic lymph nodes as well as on the primary tumors. 5-FU levels both in the regional lymph nodes and primary tumors of 18 patients with rectal cancer, who were given with the 5-FU emulsion (emulsion group) or 5-FU suppository (suppository group) intrarectally two hours before surgery, was found to be much higher in emulsion group than in suppository group. 46 patients with rectal cancer were treated preoperatively with intrarectal administration of 5-FU emulsion (25 cases) or 5-FU suppositories (21 cases) for a period of 10 days before surgery, and the histological effect of this regimen on the metastatic lesion in the lymph nodes, as well as in the primary tumor was examined. No detectable difference was found in the primary lesions between the emulsion group and the suppository group. In the metastatic lesions, however, the rate of effectiveness was higher in the emulsion group than in the suppository (68 percent versus 33 percent).     

Evaluation of clinical efficacy of a cephem antibiotic, cefmetazole, in inflammatory infections of the upper respiratory tract

We had reported the fundamental study on the utility of a new cephem antibiotic, cefmetazole (CMZ). On the basis of the results we administered CMZ to patients to investigate its clinical utility in this study. 1. CMZ was administered to 53 patients including 4 infants. They consisted of 30 cases of acute tonsillitis, 10 of peritonsillar abscess, 10 of laryngitis or pharyngitis, and 3 of sinusitis. 2. One of 2 g CMZ was administered to an adult patient except for l case and 0.5 g to an infant patient once or twice daily for at least 3 days. The method of administration was one shot intravenous injection, intravenous drip infusion or intramuscular injection. 3. The strict criteria for evaluating the efficacy of a drug were made and used for judging the efficacy of CMZ. 4. CMZ was clinically effective in 100% of patients with acute tonsillitis, 100% of those with peritonsillar abscess, 90% of those with laryngitis or pharyngitis, and 67% of those with sinusitis. 5. Bacteriologically, a single sort of bacterium was isolated in most cases of acute tonsillitis, laryngitis and pharyngitis and in the half of cases of peritonsillar abscess. Two and more sorts of bacteria were isolated in the other cases. The main bacteria isolated were beta-Streptococcus, S. pneumoniae and H. influenzae. Anaerobic bacteria, mostly Peptococcus spp. and Peptostreptococcus spp., were detected in peritonsillar abscess. 6. The clinical results agreed with the clinicobacteriological results. All the bacteria detected before treatment of CMZ disappeared. CMZ also acted effectively in cases in which H. influenzae was suspected to be a causative organism. 7. The present results of CMZ treatment were similar to those of cefazolin (CEZ) treatment published so far. 8. Thus, CMZ was confirmed fundamentally and clinically to be a very useful drug for infection of the upper respiratory tract.     

Therapeutic effect of CpG-enriched plasmid administration on the tight-skin mouse model of scleroderma

Immunostimulatory CpG motifs can preferentially induce Th1 immune responses and have been applied to treat Th2-dominant disease. In this study, we investigated whether a plasmid with the addition of 20 copies of an immunostimulatory CpG motif (pB-CpG20) might prevent the development of scleroderma-like syndrome in tight-skin (Tsk/+) mice. Administration of pB-CpG20 to Tsk/+mice every 3 weeks starting at the age of 1 week reduced skin thickness and collagen content compared to that of pB or saline. The reduction was long lasting even after halting the treatment. Furthermore, this treatment partially reduced the production of anti-nuclear antibodies although it did not decrease the incidence of lung emphysema. pB-CpG20 increased the number of spleen cells secreting IFN-gamma and reduced that of the cells secreting IL-4 in vivo and in vitro compared to saline. These results suggest that repeated administration of a CpG-enriched plasmid can ameliorate scleroderma-like syndrome by biasing Th1 immunity in young Tsk/+mice.     

Gelatin hydrogels cross-linked by gamma-ray irradiation: materials for absorption and release of dye

Gelatin hydrogels cross-linked by y-ray irradiation using 60Co as gamma-ray source were prepared. As a model of controlled release of low-molecular-weight compounds, absorption and release of methylene blue, a water-soluble cationic dye, was investigated. Irradiated gelatin hydrogels did not redissolve at temperatures over 40 degrees C, while unirradiated gels were thermoplastic and reversibly changed the stage between gel and sol. Measurement of both the wet weight after swelling in distilled water and dry weight after freeze-drying showed that the higher-dose irradiation gave stiffer and more compact gels with the lower specific water content, irrespective of the absorbed dose rate. The time-course of absorption and release of methylene blue in aqueous solution was measured. Since absorption of dye into gelatin gels was much affected by liquid phase pH, amount of absorption was higher in pH above an IEP of gelatins. Moreover, the absorption and release of methylene blue with Type-B gelatin were higher than with Type-A gelatin, respectively. Therefore, absorption and release of the dye depend on the electrostatic interaction between the dye molecule and gelatin.