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Biomedical subjects

C P Cornell

Publications and source records attributed to C P Cornell.

6 recordsLinked to original sources

Synthesis and structure-activity relationships of 7-diazabicycloalkylquinolones, including danofloxacin, a new quinolone antibacterial agent for veterinary medicine.

A series of novel 6-fluoro-7-diazabicycloalkylquinolonecarboxylic acids substituted with various C8 (H, F, Cl, N) and N1 (ethyl, cyclopropyl, vinyl, 2-fluoroethyl, 4-fluorophenyl, 2,4-difluorophenyl) substituents, as well as, 9-fluoro-10-diazabicycloalkylpyridobenzoxazinecarboxylic acids, were prepared and evaluated for antibacterial activity against a range of important veterinary pathogenic bacteria. The diazabicycloalkyl side chains investigated at the 7-position (benzoxazine 10-position) include (1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptane (2), (1S,4S)-2,5-diazabicyclo[2.2.1]heptane (3), (1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptane (4), 8-methyl-3,8-diazabicyclo[3.2.1]octane (5), 9-methyl-3,9-diazabicyclo[4.2.1]nonane (6), 1,4-diazabicyclo[3.2.2]nonane (7), 1,4-diazabicyclo[3.3.1]nonane (8), and 9-methyl-3,9-diazabicyclo[3.3.1]nonane (9). Among these side chains, in vitro potency was not highly variable; other properties therefore proved more critical to the selection of possible development candidates. However, the relative potencies observed for several of these compounds in mouse, swine, and cattle infection models correlated well with those seen in vitro. A combination of the N1 cyclopropyl group and the C7 (1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl appendage conferred the best overall antibacterial, physiochemical, and pharmacodynamic properties. Hence, danofloxacin (Advocin, 2c) (originally CP-76,136, 1-cyclopropyl-6-fluoro-7-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1] hept-2-yl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid) was selected as a candidate for development as a therapeutic antibacterial agent for veterinary medicine.

Actinobacillus Infections↗

Erythrocytes as a source of essential lipids for Treponema hyodysenteriae.

Mammalian erythrocytes were tested as a nutrient source for the spirochete Treponema hyodysenteriae, the etiologic agent of swine dysentery. Brain heart infusion (BHI) broth did not support growth of T. hyodysenteriae B204 or B78. However, BHI broth supplemented with washed bovine erythrocytes, erythrocyte membranes, or cholesterol was an excellent culture medium for these strains (4 X 10(8) to 10(9) cells per ml, final population densities). Small amounts of cholesterol (3 to 10 micrograms/ml of medium) were required for maximum cell yields of strain B204. Of various sterols and sterol-like compounds tested, cholestanol and sitosterol could substitute for cholesterol. BHI-dehydrated medium extracted with CHCl3-CH3OH (2:1, vol/vol) to remove lipids was used to prepare lipid-depleted culture broth. Lipid-depleted broth supplemented only with cholesterol did not support T. hyodysenteriae B204 growth. However, this same broth supplemented either with vesicles made from cholesterol and phosphatidylcholine or with washed erythrocytes was a good culture medium for the spirochete. Thus, both cholesterol and a phospholipid are needed for T. hyodysenteriae growth in lipid-depleted broth. Mammalian erythrocytes can be used by the spirochete as a source of these lipids.

Animals↗

International perspectives on child abuse.

This paper reviews an extensive sampling of the international literature on child abuse. The paper focuses on: (1) where the international research on child abuse is being conducted; (2) similarities and differences in definitions of abuse and violence; (3) the types of research methods and theoretical models used to study abuse; and (4) what we currently know about child abuse in other countries. The paper concludes with a discussion of how we can advance our understanding of child abuse by pursuing cross-cultural research. Awareness of child abuse, internationally, varies a great deal, often depending on the political, social, economic, and cultural milieu of the country. Also, despite noticeable trends within countries, the research techniques and theoretical models used to guide scientific investigations vary considerably from one country to the next. For these reasons, one must draw conclusions about the patterns, causes, and extent of child abuse around the world very tentatively. There is much variation as to the likelihood of children being abused, although western, industrialized nations report the highest rates of abuse. Explanations for the variation of child abuse from one country to the next emphasize cultural differences in attitudes towards, and values placed on children, and the cultural appropriateness of using violence as a means of social control.

Australia↗

Physiological and nutritional features of Corynebacterium pyogenes.

Growth and acid metabolic products were similar when Corynebacterium pyogenes was grown aerobically or anaerobically in a serum-free medium (SFM). This indicated that C. pyogenes obtains energy for growth primarily by fermentative metabolism even under aerobic growth conditions. Growth yield was reduced by 90% in SFM minus glucose, 50% in SFM minus NaHCO3, 90% in SFM minus yeast extract, 100% in SFM minus Trypticase and yeast extract, and 30% in SFM minus haemin or Trypticase. Growth was not detectable when a known mixture of amino acids, vitamins, and nucleic acid bases were substituted for Trypticase and yeast extract in SFM; addition to the latter medium of a peptide source such as Trypticase or casitone supported good growth of the organism. When NaHCO3 was omitted from SFM and dissolved CO2 in the medium was rigorously excluded, growth was undetectable indicating that C. pyogenes has an obligate requirement for CO2 for growth. Succinate, formate and acetate were the major fermentation products in SFM, whereas in SFM minus HCO-3 or haemin, lactate was the major product and only small quantities of other acids accumulated.

Aerobiosis↗

Chemically defined growth medium for Corynebacterium pyogenes.

A chemically defined medium and a relatively simple semidefined medium (SDM) which allow good growth of Corynebacterium pyogenes, a nutritionally fastidious animal pathogen, were described. The SDM contained glucose, trypticase, yeast extract, hemin, minerals, cysteine x HCl, and NaHCO3. To obtain a chemically defined medium, yeast extract in SDM was replaced with a defined mixture of nucleic acid bases, vitamins, amino acids, and trace minerals, and trypticase was replaced by myo-inositol (1 microgram/ml of medium).

Animals↗