Comparison of the quantitative dry culture methods with both conventional media and most probable number method for the enumeration of coliforms and Escherichia coli/coliforms in food.

Sanita-kun™ CC (coliform count) and EC (Escherichia coli/coliform count), sheet quantitative culture systems which can avoid chromogenic interference by lactase in food, were evaluated in comparison with conventional methods for these bacteria. Based on the results of inclusivity and exclusivity studies using 77 micro-organisms, sensitivity and specificity of both Sanita-kun™ met the criteria for ISO 16140. Both media were compared with deoxycholate agar, violet red bile agar, Merck Chromocult™ coliform agar (CCA), 3M Petrifilm™ CC and EC (PEC) and 3-tube MPN, as reference methods, in 100 naturally contaminated food samples. The correlation coefficients of both Sanita-kun™ for coliform detection were more than 0·95 for all comparisons. For E. coli detection, Sanita-kun™ EC was compared with CCA, PEC and MPN in 100 artificially contaminated food samples. The correlation coefficients for E. coli detection of Sanita-kun™ EC were more than 0·95 for all comparisons. There were no significant differences in all comparisons when conducting a one-way analysis of variance (anova). Both Sanita-kun™ significantly inhibited colour interference by lactase when inhibition of enzymatic staining was assessed using 40 natural cheese samples spiked with coliform. Our results demonstrated Sanita-kun™ CC and EC are suitable alternatives for the enumeration of coliforms and E. coli/coliforms, respectively, in a variety of foods, and specifically in fermented foods. SIGNIFICANCE AND IMPACT OF THE STUDY: Current chromogenic media for coliforms and Escherichia coli/coliforms have enzymatic coloration due to breaking down of chromogenic substrates by food lactase. The novel sheet culture media which have film layer to avoid coloration by food lactase have been developed for enumeration of coliforms and E. coli/coliforms respectively. In this study, we demonstrated these media had comparable performance with reference methods and less interference by food lactase. These media have a possibility not only to be useful alternatives but also to contribute for accurate enumeration of these bacteria in a variety of foods, and specifically in fermented foods.

Studies on topical antiinflammatory agents. III. Synthesis of 17 alpha-acyloxy-9 alpha-fluoro-11 beta-hydroxy-16 beta-methyl-1,4-pregnadiene-3,20-dione 21-thio derivatives and related compounds.

A series of 21-thio derivatives of 9 alpha-fluoro-11 beta,17 alpha-dihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione 17-esters and related compounds were synthesized and evaluated as topical antiinflammatory agents. These compounds were prepared by the reaction of 9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione (betamethasone, I) 17-ester derivatives and various mercapto compounds. A structure-activity relationship study revealed that the structural combination of a thio group at the 21-position and an ester group at the 17-position contributed to vasoconstrictive activity. Among these compounds, the 21-methylthio 17-propanoate compound (6) was found to have the most potent activity, being more potent than betamethasone 17-valerate (BV).

Studies on topical antiinflammatory agents. II. Synthesis and vasoconstrictive activity of 21-substituted corticosteroids with sulfur-containing moieties.

As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio group enhanced the activity. The activities of the 21-methylthio (3Ad) and the 21-ethylthio (3Ae) compounds were more potent than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeroyloxy-1,4- pregnadiene-3,20-dione (betamethasone 17-valerate, BV).

Studies on topical antiinflammatory agents. I. Synthesis and vasoconstrictive activity of corticosteroid 17-succinyl esters.

A series of 17-succinyl derivatives of four corticosteroids was prepared. They were tested for vasoconstrictive activity in humans, using 9 alpha-fluoro-11 beta, 21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV) as a standard. The activities of the 21-chloro 17-methylsuccinate compounds (6A, 6C and 6D) were greater than that of BV. A structure-activity relationship study showed that the activities of the 21-chloro 17-methylsuccinates were more potent than those of the corresponding 21-esters.

Studies on hypolipidemic agents. IV. 3-[4-(Phenylthio)benzoyl]propionic acid derivatives.

2-Acetylthio-3-benzoylpropionic acid derivatives having two benzene rings or condensed-ring moieties were prepared, and tested for hypolipidemic activity in normal rats. Some of these compounds were active. 2-Acetylthio-3-[4-(phenylthio)benzoyl]propionic acid (10) and its derivatives seemed to have the most potent hypocholesterolemic activities. Compound 10 showed strong activity, especially in cholesterol-fed rats.

14-Hydroxy-6-O-methylerythromycins A, active metabolites of 6-O-methylerythromycin A in human.

(14R)-14-Hydroxy-6-O-methylerythromycin A and (14S)-epimer have been isolated as active metabolites from human urine after oral administration of 6-O-methylerythromycin A (TE-031, A-56268). The structures of these metabolites were determined by means of mass, 1H and 13C NMR spectroscopies. Antimicrobial activities of (14R)-14-hydroxy-6-O-methylerythromycin A, a major metabolite, were comparable to those of the parent drug TE-031, whereas (14S)-14-hydroxy-6-O-methylerythromycin A was 4- to 8-fold less active than TE-031 against bacterial standard strains.

Studies on cephalosporin antibiotics. I. Synthesis, antibacterial activity and oral absorption of new 3-(O-substituted)-7 beta-[D-alpha-amino-alpha-(4-hydroxyphenyl)acetamido]cephalosporins.

The synthesis, antibacterial activity and oral absorption of new 7 beta-[D-alpha-amino-alpha-(4-hydroxyphenyl)acetamido]cephalosporins (1) with various O-substituents at the C-3 position of a cephalosporin nucleus are described. Of these, the cephalosporins (1b-1e) having an alkoxycarbonylmethoxy group at the C-3 position showed good oral absorption in rats as well as potent activity against Gram-positive bacteria. The structure-activity relationships of 1 are also presented.

Studies on cephalosporin antibiotics. II. Synthesis, antibacterial activity and oral absorption of 3-alkoxycarbonylmethoxy-7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(O-substituted oxyimino)-acetamido]cephalosporins.

The synthesis, antibacterial activity and oral absorption in rats of 3-alkoxycarbonyl-methoxy-7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(O-substituted oxyimino)acetamido]cephalosporins (1) are described. In this cephalosporin series, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(carboxy-methoxyimino)acetamid o] cephalosporins (1b, 1i and 1j) with a lower alkoxycarbonylmethoxy group at the C-3 position of a cephem nucleus exhibited not only potent activity against Gram-negative bacteria but also good oral absorption in rats. Structure-activity relationships of 1 are also presented.

Structure-activity studies of 4,6-disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives with analgesic and antiinflammatory activities.

4,6-Disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives showed analgesic and antiinflammatory activities when assayed by the acetic acid writhing test in mice and the carrageenin edema test in rats. To understand how the substituents affect the biological activities, the quantitative structure-activity relationships (QSAR) of 38 compounds were analyzed using the adaptive least-squares method (ALS method). The resulting QSAR suggested that some chemical modifications of 4,6-disubstituted furo[3,2-b]indole derivatives would improve their biological activities. Thus, 15 additional compounds were synthesized to reinforce and confirm the correlation. Among these compounds, particularly 4-(2-ethylhexanoyl)-2-(morpholinocarbonyl)-6-(trifluoromethy l) furo[3,2-b]indole showed pronounced biological activities. This compound gave a pharmacological activity spectrum similar to that of tiaramide but exhibited much higher potency.