Concerning a new long acting sulfa drug, su lfamethoxypyrazine (abbreviated as SMP), basic studies were performed and the following results were obtained.
1. Antibacterial sensitivity test of SMP again st Staphylococcus aureus and several gram negative bacilli showed somewhat inferior MIS values to sulfamethoxypyridazine (SMPD).
2. Serum-protein binding rate measured by means of cellophane bag dialysis was lower than general sulfa drugs being used.
3. Organ level follo wing oral administration to mice was higher in SMPD, SMP and SIM in order. It was the same tendency in every experiments that the lung, kidney and liver level were h igher in order.
4. The inhibitory effect to experimental subcutaneous infection to mice by Staphylococcus aureus and Klebsiella was better in SMPD than in SMP at both cases.

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A new penicillin derivative, methylthio-bromo- cinnamyl penicillin (P-212), which has been synthesized at Japanese laboratory was evaluated in comparison with methylchlorophenyl-isoxazolyl penicillin (MCI-PC) and the following results were obtained.
1. The minimal inhibitory concentration value against Staphylococcus aureus ranged from 0. 8 to 3. 1 mcg/m1 and resistant strains to this compound were not encountered.
2. P-212 showed smiler bactericidal activity than MCI -PC.
3. Inoculum size influenced more strongly on P-212 sensitivity test.
4. It was shown that P-2I2 has large adsorbability to red blood corpuscle, strong inactivation rate by mice liver homogenate and high serum-protein binding power.
5. Organ levels of P-212 were considerably lower at eve ry organs either by oral route or intramuscular injection than MCI-PC. Peak level determined ranked in the liver, kidney and lung in order.
6. The inhibitory effect of P-212 against intravenous or subcutaneous Staphylococcus inoculation in mice was inferior to MCI-PC.

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A new tetracycline derivative, tetracycline-gua iacolsulfonate, which has been manufactured in Spain (abbreviated as TC-GS) was investigated in comparison with tetracycline and the following results were obtained.
1. Staphylococcus aureus and several gram negative bacilli showed the same minimal inhibitory concentration value to both tetracyclines.
2. The pattern of bacterio static and-cidal action of TC-GS was similar to TC.
3. TC-GS showed little adsorption to red blood corpuscle, no inactivation by lever homogenate. The serum-protein binding rate was 26% by cellophane bag dialysis method.
4. TC-GS was inactivated by Mg, Ca and Al ions as in the same g rade as TC.
5. When cross over test was performed using TC soft capsule and TC-GS enterocoating tablet, the latter was poorly absorbed. Even when the cross over test was tried using capsules specially prepared from standard antibiotic powder, blood concentration was yet lower in TC-GS, while urinary excretion level was higher in TC-GS occasionally.
6. At organ level determination in mice following oral administration, slightly higher peak level was obtained in TC-GS in each organ. Those of liver, kidney, spleen, lung and serum ranked in these order.
7. The inhibitory effect of TC-GS to abscess formation following Staphylococcus subcutaneous injection to mice was as good as TC.

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This paper described some experimental results of urinary excretion after oral administration of a new urinary tract antiseptic “Hippramine” to rabbit.
1) Following administration of drug, 1 g, 3 g and 5 g to rabbit, weighing 3 kg( _??_ ), the urinary recoveries were 29. 40%, 36. 70% and 19. 09% within 24 hours respectively, and the urinary concentrations were 0, 78 mg/ml, 1. 93 mg/ml and 1. 62 mg/ml respectively. The urinary excretion continued in lower concen trations for several days.
2) Within 24-48 hours after administration of drug, the urinary p H inclined to alkali, and then returned to 7. 0 afterwards.

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The authors report 3 cases of typhoid and paratyphoid carriers treated with hetacillin. In two, cholecystectomy was performed to investigate the bacilli in the gallbladder. To investigate the problem further, an attempt was made to isolate the bacilli from gall-stones.
The authors summarize their experience gained in the tr eatment of 3 patients with hetacillin and consider that the chemotherapeutic effect of both hetacillin and AB-PC depends on the size of stones in the gall-bladder.

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Single oral dosages of 1. 0 g of sulfamethopyrazine (SMP) were given to 5 normal adults, and blood and urine levels were determined by cup method.
Blood and urine samples were collected 1, 2, 3, 6, 9, 12 hours after administration. Highest blood level was attained after 3 hours (51. 8 mcg/ml, mean value for 5 adults), and highest urine level was 28. 8 mcg/ml.
Then, we treated 30 patients affected with urinary tract infections. They received 800 mg of SMP during first 24 hours and 200 mg on the following 3-5 days. In acute cystitis, 15 out of 22 patients obtained good results, but 6 patients of chronic cystitis and 2 patients of chronic pyelonephritis were proved not satisfactory.
In only one patient, exanthema was observed, but other side effects were not seen.

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Hepatic dysfunction has been frequently reported in clinical use with esters of erythromycin (EM) and oleandomycin, and these side effects have been explained with the concept of hypersensitivity by some observers.
It is said that biliary excretion of propionyl erythromycin (EMP) in human subjects is remarkably different from that of EM base, suggesting the metabolic process in these two drugs may be quite different.
This paper deals with the difference in metabolism between EM and EMP in vitro and in vivo, in regard to the cause of hepatic dysfunction due to the latter.
1) In absorption and excretion study with dogs, pro longation in half-life and marked decreases in biliary and urinary excretion have been observed following intravenous EMP dose in comparison with EM base, while blood levels of the two substances in portal vein were similar following intraduodenal dose.
2) In the study with rats and rabbits, decrease in blood level of EM was found in animals with phenobarbital pretreatment.
N-methylase activities of the rat liver were accelerated by the treatment with phenobarbital but not erythromycins. Esterase activities were unchanged in all these treatments.
3) The study of in vitro and in vivo metabolism of erythromycins with thin layer chromatography was carried out.
The results seem to indicate that EM is changed into two metabolites, i. e. des-N-methyl erythromycin and one unknown, but EMP may not be changed into EM directly, and may be passed through other metabolic process.

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Antibiotic susceptibility and phage types were studied in 329 strains of staphylococci isolated in Hokkaido during a period from January to December 1966. To penicillin G 74. 9% of the strains were resistant, to streptomycin 55. 5%, to tetracycline 71. 0%, to chloramphenicol 33. 8%, to erythromycin 54. 9% and to kanamycin 23. 4% at a concentration of 50 units or mcg per ml. No resistant strain was found against methyl-phenyl-isoxazolyl penicillin or cephaloridine. Strains from the Hokkaido University Hospital (with 800 beds) were found to be more resistant than those from other hospitals of smaller bed sizes.
Only 42. 9% o f strains was typed by means of the basic phage set with an occurrence of the phage type 80/81 in 26. 7%. The incidence of untypable strains was higher in those isolated in the Hokkaido University Hospital than those from other smaller bed size hospitals. A significant correlation was found between antibiotic susceptibility and phage types. The strains of 80/81 group were highly resistant to the above mentioned antibiotics, while the phage-typable strains other than 80/81 were generally sensitive. Most of the untypable strains were multi-resistant, suggesting the] prevalence of new groups of staphylococci which are highly resistant and phage-untypable.

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Twenty two hours after partial hepatectomy, the rat-liver was removed and DNA was extracted by phenol method. DNA was divided into two fractions by means of Ecteola cellulose column. A pretreatment of the rats with 6-mercaptopurine deoxyriboside, actinomycin S, chromomycin A3 or nalidixic acid inhibited solely the synthesis of DNA eluted with alkaline saline, whereas an administration of 2-isonicotinoyl-hydrazino-5-nitrosotropone inhibited mostly the synthesis of DNA eluted with dilute saline.
When the nuclei of the regenerating rat liver was divided into chromatin fraction and nucleolar fraction, 6-mercaptopurine deoxyriboside inhibited exclusively the chromatin DNA synthesis but the synthesis of nucleolar DNA was relatively intact.

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The activity of sulfamethopyrazine(SMP) against clinical pathogenic bacilli isolated from respiratory tract was measured. Pathogenic staphylococci and E. coli were inhibited by more than 50 mcg/ml, but pneumococci and streptococci were inhibited by 12. 5 mcg/ml. Cross resistance between SMP and Sulfisomezole( SIM) was observed.
Considering the result of the in vivo therapeutic experiment in infected mouse with pathogenic staphylococci, we thought SMP had more efficacy than SIM.
A total of 35 patients were treated with SMP. Patients were as follows.: upper respiraty infection 22; acute purulent tonsillitis 10; chronic bronchitis 1; bronchiedtasis 2. SMP was effective in almost all patients except one URI, especially effective for purulent tonsillitis.
Neither side effect nor toxicity of SMP were found.

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The effects of mitomycin C (MMC) on DNA synthesis and mitotic cycle of rat liver cells during the period of regeneration after partial hepatectomy were investigated by autoradiography with tritiated thymidine and biochemically.
(1) MMC in jected intra-peritoneally before extensive DNA synthesis took place, depressed subsequent DNA formation and cell division.
(2) MMC injected during th e period of DNA synthesis delayed and inbibited the initiation of cell division.
(3) MMC injected before hepatectomy inhibited division of the regenerating liver cell after hepatectomy. These inhibitory activities of MMC proved most effective in comparison with those of other anticancer drugs.

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Methenamine has been known to be a clinical urinary antiseptic drug for a long time, and today it still holds the important position in the medical world.
Hippramine, hippuric acid salt of methenamine, likewise provides the antibacterial effectiveness of methenamine, and the acidifying property of hippuric acid.
When 2 g of Hippramine was given orally to man, th e pH of the urine reached 6. 0 -6. 3 after 2 hours..
In vitro sensitivity of 28 g negative microbes to Hippramine was tested by nutrient agar plates con taining serially diluted drug and 0. 15 molar phosphate buffer of pH 5, 6 and 7.
And we compared Hippramine with Uronamin which has been already evaluated clinicaly to obtain the similar results.
The drug was administered to 21 patients, including 6 acute and 15 chronic pyelonephritisicases. The effectiveness was demonstrated in 53% of chronic cases and in 67% of acute cases.
The prophylactic effect of the drug for relapse in pyelonephritis cases was sa tisfactory to obtain 100% prevention in the cases.

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Fifty patients who admitted to our clinic from September 1963 to March 1966 and subjected to an indwelling Foley's catheter were divided into two groups, one being treated by predonisolone-fradiomycin ointment, and the control group. The incidence of purulent urethral discharge was compared in the two groups. One gram of this ointment contains 2. 5 mg of predonisolone and 3. 5 mg of fradiomycin sulfate. During the retention of the urether catheter, small amount of the ointment was applied over the external urethral meatus 4 times daily. In 2 of the 30 cases treated, 6. 7%, and in 6 of the 20 non-treated cases, 30. 0%, purulent discharges were observed. This difference was statistically significant with p<0. 05. The application of this ointment over the external urethral meatus appears to prevent the edema, pruritus, flare and infiltration through the action of predonisolone and to prevent the infection of the both gram positive and negative organisms by the broad-spectrum bacteriocidal action of fradiomycin. It is well assumed that those two actions played a big role in the prevention of urethritis following an indwelling catheter. This effect is very important not only because it alleviates a local unpleasant feeling but also eliminates a main cause of pyelonephritis.

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Endoxan(EX)is said to be almost inactive in vitro, and the agent becomes biologically active in vivo only on appropriate activation, which is thought to be accomplished probably by the liver. The present investigation deals with the effect of steroid hormone on activation of EX.
The in vitro experiments, in which EX was incubated with rat liver slices, indicated that the addition of prednisolone caused a definite inhibition of EX activation. The in vivo experiments, in which serum concentrations of EX after intraperitoneal administration in normal rat were determined by means of chromatography, demonstrated that the simultaneous administration of prednisolone with EX resulted in a significant reduction of the concentration ratios of active metabolites to total EX (active metabolites + inactive form of EX) in sera. The results obtained from these experiments indicate that the activation of EX appears to be inhibited by steroid hormone (prednisolone).
The mechanism of activation of EX with reference to the inhibi tory action of steroid hormone has been briefly discussed.

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