N₁-(2-Tetrahydrofuryl)-5-fluorouracil (FT-207), a new antimetabolic anticancer agent synthesized in USSR, was studied on antimicrobial activity in vitro and distribution, excretion and metabolism in vivo.
The results obtained were as follows.
1) Antimicrobial activity
FT-207 showed fairly active against Micrococcus flavus ATCC 10240, Sarcina lutea PCI 1001, Staphylococcus epidermidis and Staphylococcus aureus 209 P, but in general the activity was inferior to that of 5-FU.
2) Distribution
By the intravenous administration of FT-207, 400mg/kg, in normal and AH-130 bearing rats, the concentration of FT-207 in serum and tissues maintained measurably until 16-24 hours.
On the other hand, the active substances (5-FU, etc.) from FT-207 detected at 1-4 hours and peaked at 4-16 hours in tissues.
3) Urinary excretion
FT-207 and its active substances were excreted in urine for a long time, and the recoveries of FT-207 for 48 hours in rats, mice and rabbits were 12-18%.
4) Metabolism
In normal and AH-130 bearing rats, the main active substance from FT-207 administrated intravenously was 5-FU.

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The β-lactamase mediated by the R factor in clinically isolated E. coli Strain No. 24 has been purified and characterized.
The enzyme was purified by the following procedure : gel filtration on Sephadex G-100, chromatography on DEAE-cellulose, starch gel electrophoresis and gel filtration on Sephadex G-75. The molecular weight was estimated to be 23, 8000 by gel filtration on Sephadex G-75. By starch gel electrophoresis, the isoelectric point was found at pH 5.3. The MICHAELIS constants for benzylpenicillin, ampicillin, phenethicillin, 6-aminopenicillanic acid and cephaloridine were determined.
The enzyme showed a broad specificity of the action against both penicillin and cephalosporin derivatives, and the ratio of this activity as penicillinase and cephalosporinase did not change through the purification steps. Cloxacillin, the semisynthetic penicillin, acted as a competitive inhibitor of the hydrolysis of benzylpenicillin and cephaloridine.
These results and other our studies suggest that both activities as penicillinase and cephalosporinase present in the same active site on a single enzyme.

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It is well known that kasugamycin is an effective anti-rice blast drug with extremely low toxicity to rice, other plants, rats, dogs and monkeys, but the reports dealing with the subacute toxicity of this drug are few, especially in long term oral administration in experimental animals. The results of the experiment on this subject using mice and rats are as follows.
1) When this drug was administered at a dose less than 100 mg/kg for 3 months, no inhibitory signs were seen in normal growth of the animals.
2) The possibility that kasugamycin directly produced blood disturbance, was negligible.
3) The urine was normal through the experimental period.
4) It is undeniable that disturbances of the digestive tract including anorexia, and parenchymal disorder of the liver occurred at a dose more than 100 mg/kg.
5) At a dose more than 100 mg/kg, a marked BUN elevation, and a slight increase in serum inorganic phosphorus were seen, these results revealing clearly that the excretive disorder of the kidney was incited by the drug.
6) Three months' administration did not influence the weight of the liver, kidney, and adrenal.
7) In the animals given 10, 000 mg/kg, serious damage of the kidney was noticed; that is, discolored cytoplasm of the epithelium of the tubulus cell and dilated lumen of the tubulus.
From these findings, it is conceivable that the oral maximal safety dose of the drug is less than 100 mg / kg / day ; dosis in this range may not cause any lesion in man.

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The effect of erythromycin for the subcutaneous abscess in mice caused by Staphylococcus aureus was examined by varying several factors, the number of infected cells, the dose, and the time of administration, and it was revealed that the effect of the drug for abscess formation was affected by the above factors, assuming a very complicated aspect, which are summarized as follows :
1. On large dose, the administration before infection is the most effective.
2. Administration of small dose seems to be effective immediately after infection, and the effect may be related to the time sustaining effective level in serum.
3. Administration after infection is not so effective regardless of the dose.
4. The abscess formation by large number cells infection (10^8.5) seems to be different in nature from that by small number cells infection, and consequently the effect of the drug may be differently observed according to the amount of bacteria infected.
The above each point was discussed in this paper.

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A mixture of leucomycin and chloramphenicol was active as same as chloramphenicol against leucomycin resistant staphylococci. Inactivation of chloramphenicol by chloramphenicol resistant staphylococci was reduced by the addition of small amounts of leucomycin.
Chemotherapeutic effect of leuchlon on staphylococcal infection in mice was almost the same to that of chloramphenicol.
Leucomycin resistant mutants were isolated from the kidneys of mice infected with erythromycin inducible-resistant staphylococci after leucomycin therapy. In contrast, these mutants were not detected when leuchlon was used instead of leucomycin.

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For the purpose of studies on prevention of recurrent urinary tract infections, effect of hexamine (Methenamine) mandelate was evaluated to the infections in vitro and in vivo.
Ascorbic acid was considered to be a suitable urine acidifying drug that enhances the activity of hexamine mandelate. The considerable amount of formaldehyde (average 308.3 mcg per ml) was detected in the urine following the administration of hexamine mandelate and ascorbic acid. The concentration was enough to inhibit growth of the various causative organisms in the infections ; that is, bactericidal against E. coli, Proteus, and Klebsiella, whereas bacteriostatic against Pseudomonas.
Hexamine mandelate (4 g/day) and ascorbic acid (3.2 g/day) were administrated daily to 19 patients with recurrent urinary tract infections followed by injury of the spinal cord in the periods ranging from 6 to 30 months. The number of fever attacks of the patients were decreased significantly by the administration, accompanying less necessity of the usage of antibiotics.
Hexamine mandelate and ascorbic acid appeared to be effective prophylaxis agent in recurrent urinary tract infection with low incidence of side effects.

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Therapeutic effectiveness and side effect of doxycycline and minocycline in the treatment of patients with respiratory infection were assessed in a double-blind trial. Both the doxycycline and minocycline groups were divided into two groups of those receiving a single 200 mg dose daily on day 1 and subsequently 100 mg dose daily, and those given a daily dose of 200 mg throughout a treatment period.
Seventeen patients (referred as D₁ group) in the doxycycline group were treated with an initial 200 mg/day followed by a single 100 mg/day and 22 patients (D₂ group) with a single 200 mg daily dose throughout a treatment period while 17 patients (M₁ group) in the minocycline group received the former dosage regimen and 20 patients (M₂ group) the latter.
None of patients in the two groups was medicated the drug for more than 7 days. In overall assessment, 79.0% of improvement rates were obtained with D₁ group and 64.7% with M₁ group. Those with D₂ and M₂ groups were 72.7% and 80.0%, respectively. The improvement rates of each total drug group (D₁+D₂ and M₁+M₂) were 75.6% with doxycycline and 73.0% with minocycline. There was no statistical difference between the two groups.
Fourteen percent of the doxycycline treated patients complained of side effect and the rate of the minocycline group was 15.4%. Such secondary effects occurred more frequently with the patients when given a 200 mg daily dose. One subject in M₁ group complained of dizziness and this symptom was reported by 5 out of 20 patients in M₂ group.
In a double-blind study of 78 patients with respiratory infection, both doxycycline and minocycline were found to be equally effective and any difference which is statistically significant was not observed in the therapeutic effectiveness. Dizziness was reported specifically by those receiving minocycline.

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A synergistic effect of ampicillin and dicloxacillin on pathogenic bacteria has been studied in vitro.
Growth of the high penicillin resistant bacteria, namely, E. coli strain 0205, Proteus morganii and Enterobacter aerogenes were inhibited with the relatively low concentrations of the mixture of ampicillin and dicloxacillin.
This synergism can be explained by the fact that dicloxacillin inhibits the enzymatic hydrolysis of ampicillin by β-lactamase prepared from these bacteria, particularly, strong inhibition was observed against enzymes have a relatively slow hydrolysis rate for ampicillin.

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Absorption and excretion of the combination composed of AB-PC and MDI-PC has been studied in rats, rabbits and men. Both penicillins administered orally have given sufficient concentrations in blood, urine and bile.
The combination composed of 2 parts of AB-PC and 1 part of MDI-PC has shown high and equal blood levels for both penicillins in men.
Furthermore, the antimicrobial substances recovered from the urine of rabbit were identified as the administered AB-PC and MDI-PC by thin-layer chromatography and bioautography.

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The combination therapy of AB-PC and MDI-PC has been studied with clinically isolated pathogenic bacteria in mice by oral administration, and shown marked synergistic effects against AB-PC resistant strains, E. coli strain 0205 and P. morganii strain 0237, and also considerable effect against S. aureus 226.
Though the amount of AB-PC in combination drug is of course lower than that of AB-PC alone used as reference, the former has shown similar effect to the latter against D.pneumoniae III, S. aureus Smith, S. hemolyticus S 23 and S. typhimurium H.
Based on the antimicrobial activity, broad antibacterial spectrum in vitro and the distribution pattern in vivo of AB-PC, the 2 : 1 combination (AB-PC : MDI-PC) was assumed to be suitable for clinical use rather than 1 : 1 combination.

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