Broiler chickens are raised under extremely intensive conditions with the emphasis in utilizing every day of their short 35-40 day lifespan to realize the potential of maximum weight gain. If the birds fall behind the planned growth rate there may be reduced profits for the fanner. Therefore, in many modern systems. mean body weight is constantly monitored, and within hours ofdetecting a reduction in projected weight gain, veterinarians and nutritionists can be alerted to fiid the cause of the setback. If a bacterial disease is diagnosed, the whole flock is o h n given feed or water medicated with an antibacterial drug. Ifthe response to this drug is not optimal. or antibiotic sensitivity tests indicate otherwise, another antibacterial agent may be administered. The emcacy of these drugs is dependent upon the dosage administered, the susceptibility of the pathogenic organism to that drug, the pharmaccdynamics of the drug in the broiler (a fairly constant factor which would have been examined in detail by the manufacturer), its pharmacokinetics in the broiler, and acquiring and maintaining a minimum inhibitory concentration (MIC) in the blood. Pharmacokinetics largely involves phase 1 metabolism in the liver mediated by enzymes, collectively called mixed function oxidases (MFO). The activity of the MFO can be elevated or depressed after exposure to many xenobiotics, and the metabolism of certain drugs given concomitantly or thereafter might also be changed.In view of the above facts, it is surprising that the topic of the effects of xenobiotics on MFO in broilers has been so little investigated. Our literature search revealed only three publications on MFO in commercial broiler chickens (Takahashi & Jensen, 1984; Brenes et d., 1985; Brenes et PI., 1990), with no mention of chemotherapeutic agents. Although considerable data exist on the effects of xenobiotics on MFO activity in laboratory animals (Yang et d., 1992), species dflerences (Walker, 1980) preclude a valid extrapolation to broilers and there clearly exists a tremendous knowledge deficit on this topic. Quinolones have been shown to inhibit Ndemethylation In humans (Staib et d.. 1987) and in laboratory anfmals (Mizukl etal.. 1989). but no such studies have been published on this promising group of antimicrobials which are now used in broilers. This work presents data on the d e c t of the ff uomquinolone antibiotic emfloxacin on the activity of MFO in broilers. Onedaydd male commercial broiler chicks were housed in electrically heated battery brooders. Broiler feed was supplied ad libitum throughout. When the birds were 25 days old, they were weighed and birds were chosen in a weight range of 525-650 g. Five gruups of 6-10 birds w e n randomly constituted. Four groups were dosed per os with emfloxacin (Barn, Bayer, Germany), according to the manufacturers' recommendations, at a dose of 10 mgkg body weight each day for 3 consecutive days: these groups diflered only in the time between emfloxacin dosage and MFO determination. One control group received no tr...

The fluoroquinolone antimicrobials norfloxacin and enrofloxacin were found to inhibit hepatic microsomal cytochrome P-450 monooxygenases in the livers of broiler chickens using dosages as given in commercial flocks. Norfloxacin inhibited the process of N-demethylation of aminopyrine to a greater degree, while enrofloxacin more markedly inhibited hydroxylation of aniline.

BackgroundBiomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients.MethodsThis research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment.ResultsThe administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes.A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group.ConclusionsThe DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.

The concomitant administration to broilers of ionophore coccidiostats and certain chemotherapeutic agents may cause deleterious interactions, with toxicosis and death as possible sequelae. In this study, co-administration of the ionophore monensin was not shown to alter blood levels of enrofloxacin or norfloxacin. In addition, exposure to lasalocid was not shown to change blood levels of enrofloxacin. However, norfloxacin + lasalocid co-administration induced aminopyrine N-demethylase (AD) activity by day 5 after the last administration of norfloxacin, and induced a rise of norfloxacin levels in the blood. This rise of blood norfloxacin levels after co-administration of norfloxacin + lasalocid implies that lower levels of norfloxacin could be administered in birds also receiving lasalocid.

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