Evaluation of two doses of ceftiofur crystalline free acid sterile suspension for treatment of metritis in lactating dairy cows.

The objectives of this study were to evaluate efficacy of a 2-dose regimen of ceftiofur crystalline free acid sterile suspension (CCFA-SS) for treatment of acute metritis in lactating dairy cows under field conditions and to provide additional safety and injection site tolerance data for injections at the base of the ear. Cows at 15 dairies with rectal temperature ≥ 39.5°C and fetid uterine discharge ≤ 10 d postcalving were randomly assigned by blocks of 2, based on order of entry and without regard to parity, to treatment with saline (1.5 mL/45.5 kg of body weight, n=509) or CCFA-SS (6.6 mg of ceftiofur equivalents/kg of body weight, n=514). Treatments were administered by subcutaneous injection in the posterior aspect of the ear where it attaches to the head; the first dose was administered on study d 0 and the second dose was administered in the contra lateral ear on study d 3. Rectal temperatures were recorded on study d 1 to 4 and 5 or 6 and cows were clinically evaluated daily from study d 1 to 13. Cows that exhibited increased adverse clinical signs of poor health or complications associated with metritis were categorized as a treatment failure and administered escape therapy. Each cow received a veterinary physical examination on study d 5 or 6 to determine if she should be removed from the study and on study d 14 to determine clinical cure or failure to cure. Clinical cure was defined as rectal temperature <39.5°C and non-fetid and purulent or mucopurulent discharge on study d 14 and no escape therapy administered. The injection procedure was scored after each injection (study d 0 and 3) and injection sites and ear carriage were scored on study d 5 or 6, 14, and 57±3. Of the 1,023 cows enrolled, 7 were completely censored due to protocol deviations and 34 were removed for protocol deviations or medical conditions not related to metritis. Clinical cure rate was higher for CCFA-SS than for saline (74.3 vs. 55.3%) and rectal temperatures for each of study d 1 to 5 or 6 were lower for CCFA-SS than saline. Injection procedure indices showed that CCFA-SS could be practically and safely administered using commercial dairy facilities. Although injection site scores were higher for CCFA-SS than saline at study d 5 or 6 and 14, ≥98.6% of ears were normal on d 57±3. Thus, a 2-dose treatment with CCFA-SS given 72h apart increased metritis clinical cure rate and was well tolerated in dairy cows.

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.

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.

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.

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.

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).

Hemin-dependent growth stimulation and cytochrome synthesis in Corynebacterium pyogenes.

Growth of Corynebacterium pyogenes, an important pathogen in animals, was greatly increased on addition of hemin to a medium of tryptose plus mineral. The synthesis of a type b cytochrome in this organism appeared to depend on the presence of hemin in the growth medium.