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The in vitro and in vivo activities of a new naphthyridone, BMY 40062, were compared with those of ciprofloxacin and ofloxacin. BMY 40062 showed about threefold more activity than ciprofloxacin showed and four- to eightfold more activity than ofloxacin showed against staphylococci, streptococci, and enterococci. BMY 40062 showed generally twofold less activity than ciprofloxacin showed against most species of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. but twofold more activity than ofloxacin showed against these organisms. BMY 40062 and ofloxacin were more active than ciprofloxacin against Bacteroides fragilis and Clostridium difficile. The antiureaplasmal and antichlamydial activities of BMY 40062 were similar to those of the tetracyclines and were 4- and 16-fold, respectively, higher than those of ciprofloxacin. The in vitro activities of BMY 40062 were influenced by pH and magnesium, although these factors appeared to affect the activity of BMY 40062 against P. aeruginosa to a lesser extent than those of ciprofloxacin and ofloxacin. BMY 40062 was found to be bactericidal, and cross-resistance with other fluoroquinolones was observed. In mouse protection tests, the efficacy of BMY 40062 reflected its in vitro potency. BMY 40062 exhibited longer half-life, higher maximum concentration in serum, greater area under the curve, and better bioavailability in mice after oral dosing than ciprofloxacin. Compared with ofloxacin, BMY 40062 had a lower maximum concentration in serum but a much longer half-life in mice. BMY 40062 was more effective than ciprofloxacin and ofloxacin in penetrating mouse macrophages and killing macrophage-associated Staphylococcus aureus.

In this paper, some mathematical properties of the shortest-length addition chain are found for certain integers whose binary patterns meet some special forms; and the correctness of these properties is proved.

Biological and physicochemical properties of BL-S786 were compared with those of cephalothin, cephaloridine, and cefazolin. With few exceptions, BL-S786 was more active than the reference compounds against major gram-negative pathogenic species and its antibacterial spectrum was broader than that of cephalosporins currently available for clinical use. Although BL-S786 was generally less active than the control cephalosporins against gram-positive pathogens, it inhibited their growth at concentrations that should readily be achieved in humans after standard parenteral dosage. Streptococcus faecalis, a species relatively unsusceptible to cephalosporins in general, was an exception. BL-S786 was an effective bactericidal agent for strains of various gram-negative organisms. After intramuscular administration to mice, BL-S786 achieved high concentrations in blood, and its biological half-life was longer than that of the other three cephalosporins.

Fractionation of chromatin into urea-soluble chromosomal nonhistone proteins (UP), histones (HP), and DNA-associated nonhistone proteins (NP) revealed that the NP fraction from testicular and prostatic chromatin contains organ-specific acceptors for complexes of 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and its receptor. This acceptor capacity of androgenic tissue chromatin could be transferred to chromatins from non-target tissues with the NP fraction of DNA-associated proteins. Phosphorylation of chromatin enhanced its hormone-receptor binding capacity.

BMY 28100, a new oral cephalosporin with a (Z)-propenyl side chain at the 3 position and a p-hydroxyphenylglycyl substituent at the 7 position, was evaluated in comparison with cefaclor and cephalexin and, when appropriate, ampicillin and vancomycin. In vitro, BMY 28100 was more active than the reference cephalosporins against streptococci, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, Haemophilus influenzae, Propionibacterium acnes, Clostridium perfringens, and Clostridium difficile. BMY 28100 was comparable to cefaclor and more active than cephalexin against Staphylococcus saprophyticus and ampicillin-susceptible strains of Branhamella catarrhalis; but against ampicillin-resistant strains of B. catarrhalis, BMY 28100 was comparable to cephalexin and more active than cefaclor. Against Neisseria gonorrhoeae, BMY 28100 was comparable to cephalexin, but less active than cefaclor. Members of the family Enterobacteriaceae overall were equally susceptible to BMY 28100 and cefaclor but were less susceptible to cephalexin. In human serum, BMY 28100 was 45% protein bound. After an oral dose to mice, 82% of the drug was recovered in urine. The oral therapeutic efficacy of BMY 28100 in systemically infected mice reflected its activity in vitro.

BMY 28142, a new broad-spectrum semisynthetic cephalosporin, was evaluated in vitro and in vivo in comparison with ceftazidime, cefotaxime, moxalactam, and cefoperazone. The activity of BMY 28142 compared favorably with the activities of the other compounds against both Pseudomonas aeruginosa and Staphylococcus aureus and was somewhat greater against members of the family Enterobacteriaceae. The influence of inoculum size on MICs of BMY 28142 was small for most of the isolates tested, except Enterobacter species. With Enterobacter strains, a marked inoculum effect was found with all of the compounds, and the effect was more pronounced in broth than agar. Still, MICs of BMY 28142 in broth did not exceed 16 micrograms/ml. Of 37 Enterobacteriaceae strains resistant to one or more of the comparison beta-lactams, none were resistant, at a low inoculum size (10(4) CFU), to BMY 28142, compared with 3 for moxalactam, 18 for ceftazidime, 23 for cefotaxime, and 34 for cefoperazone; at an inoculum size of 10(6) CFU, the number of resistant strains was 12, 17, 25, 34, and 37, respectively. Binding to human serum proteins approximated 19%. Recovery of 73% of the drug in mouse urine indicated good bioavailability. The in vitro profile was sustained in vivo by the results obtained with experimental infections in mice. BMY 28142 was as effective as ceftazidime against systemic infection with P. aeruginosa and as effective as cefotaxime against systemic infection with S. aureus. Overall, infections with 18 of 20 strains representing nine genera were responsive to BMY 28142 at doses equivalent to or lower than those of the most effective of the comparison compounds.

We explored the antibacterial activity of phosphanilic acid (P), an analog of sulfanilic acid, alone and in combination with trimethoprim (T; TP, 1:5) with sulfamethoxazole (S) and co-trimoxazole, the combination of this sulfonamide with trimethoprim (TS, 1:5) as the reference. P resembled S in spectrum but, in addition, had significant activity against Pseudomonas aeruginosa. The overall frequency and degree of synergism with TP were lower than with co-trimoxazole. P, like S, was strongly affected by changes in inoculum size and was not bactericidal. P was well absorbed parenterally but not orally in mice. Despite low (but prolonged) blood levels, P, given orally to mice, was effective in treating infections caused by P. aeruginosa. However, against most experimental infections the therapeutic effectiveness of P, as well as that of TP, administered either intramuscularly or orally was unimpressive. Based on in vivo data, the therapeutic application of P or TP would appear to be limited.

The bioavailability and therapeutic properties of BL-S 640 in rodents were compared with those of cephalothin, cephaloridine, and cefazolin after parenteral administration, and cephalexin after oral administration. When given intramuscularly in dosages of 5 to 40 mg/kg, peak concentrations of BL-S 640 in the blood of mice were proportional to dose, but when given orally, they were proportional only up to a dose of 25 mg/kg. After either route of administration, the concentration of BL-S 640 in the blood declined at a slower rate than that of the control compounds. Rats receiving BL-S 640 orally excreted an average of 39% of the drug in the urine. BL-S 640 was highly effective in the treatment of mice infected systemically with a variety of pathogenic bacteria, its therapeutic efficacy in comparison with that of other cephalosporins being frequently in excess of what would have been predicted on the basis of comparative activities in vitro.

The ‘malic’ enzyme (EC 1.1.1.40) has been purified (300-fold) from wheat germ and its abilities to catalyse the decarboxylation and the hydrogenation of oxaloacetic acid and oxaloacetate esters was studied. The free 1-carboxyl group is essential for the interaction of oxaloacetates and substituted oxaloacetates with the enzyme via cations. The free 4-carboxyl group is required for the decarboxylation but is not indispensable for the hydrogenation. At high concentrations, cations inhibit the enzymic hydrogenation of oxaloacetic acid but not that of 4-ethyl oxaloacetate. A plausible inhibitory mechanism is proposed.