Investigating the potential role of vitamin E in modulating the immunosuppressive effects of tylvalosin and florfenicol in broiler chickens.

Tylvalosin (TVS) is a third-generation macrolide drug used for prophylaxis and treatment of mycoplasma, however; it is supposed to possess an immunosuppressive effect. In the current study, the immunosuppressive effect of TVS and florfenicol (FFC) and the potential immunomodulatory role of Vit E were investigated. The experiment included one day old chick groups treated with either TVS, FFC, Vit E, TVS/Vit E, FFC/Vit E and control non-treated group. Chicks were vaccinated with inactivated H9N2 avian influenza (AI) vaccine and humoral antibody titers to viral antigen as well as innate immunity (serum lysozyme activity and nitric oxide levels) were evaluated. Total and differential leucocytic counts, serum liver enzymes level, blood leucocytic DNA damage and cellular area percentages within the lymphoid organs were also screened. Treatment with TVS and FFC significantly decreased immune response of chickens while treatment with Vit E improved the humoral immune response at 4 and 5weeks post-vaccination. Vit E also significantly increased the cellular immune response. The combination of Vit E with either TVS or FFC modulated their immunosuppressive effect and resulted in mild immunostimulatory effects. TVS alone induced a genotoxic effect on chickens' blood leucocytes and the genotoxicity was inhibited by combination of TVS with Vit E. Histopathology revealed that chickens treated with either TVS or FFC exhibited toxic effect on the lymphatic tissues.

Pharmacokinetics of difloxacin in healthy and E. coli-infected broiler chickens.

1. The pharmacokinetics of difloxacin were investigated in healthy and E. coli-infected broiler chickens following intravenous and oral administration of a single dose of 10 mg/kg bodyweight. 2. After intravenous injection of difloxacin, the serum concentration-time curves were best described by a two-compartment open model. The distribution and elimination half-lives (t0.5α) and (t0.5el), respectively, were 0.10 ± 0.016 h and 3.7 ± 0.08 h in healthy chickens compared with 0.05 ± 0.005 h and 6.42 ± 0.71 h in E. coli-infected birds. The volumes of distribution Vdss were 3.14 ± 0.11 and 9.25 ± 0.43 l/kg, with total body clearance (Cltot) of 0.65 ± 0.018 and 1.14 ± 0.1 ml/kg/h, respectively. 3. Following oral administration, difloxacin was absorbed with t0.5(ab) of 0.57 ± 0.06 and 0.77 ± 0.04 h and was eliminated with t0.5(el) of 4.7 ± 0.34 and 3.42 ± 0.19, respectively, in normal and infected chickens. The peak serum concentrations were 1.34 ± 0.09 and 1.05 ± 0.06 µg/ml and attained a Tmax of 2.27 ± 0.07 and 2.43 ± 0.06 h, respectively. The systemic bioavailability of difloxacin following oral administration was 86.2% in healthy chickens and 90.6% in E. coli-infected birds. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of difloxacin against the field strain of E. coli O78 in vitro were 0.02 µg and 0.04 µg/ml, respectively. 4. These results show that administration of a therapeutic dose of difloxacin is effective in the treatment of E. coli infection in chickens. The serum concentration of the drug was much higher than the MIC of the E. coli O78 strain in both healthy and infected chickens.

Comparative pharmacokinetics of orbifloxacin in healthy and Pasteurella multocida infected ducks.

The pharmacokinetic aspects of orbifloxacin were studied in both healthy and naturally diseased ducks after a single intravenous and intramuscular dose of 5 mg kg⁻¹ body weight. The serum concentrations of orbifloxacin following single intravenous and intramuscular injections were higher in diseased than in healthy ducks. The disposition of orbifloxacin after a single intravenous injection was described by a two-compartment open model in both healthy and diseased ducks. Orbifloxacin was distributed and eliminated at a significantly slower rate in diseased than in healthy ducks. The total body clearance (Cl(B)) was lower in diseased (0·131 l kg⁻¹h⁻¹) than healthy ducks (0·191 l kg⁻¹h⁻¹). Following intramuscular administration of orbifloxacin, the peak serum concentration (C(max)) was higher in diseased than in healthy ducks, and this was achieved at a maximum time (t(max)) of 1·114 and 0·993 h, respectively. The drug was eliminated at a significant slower rate in diseased ducks (elimination half-life t (0·5(el))= 5·07 h) than in healthy ducks (elimination half-life t (0·5(el))= 4·18 h). These results indicate that drug elimination patterns in healthy and diseased ducks are not the same. The pharmacokinetic profile of the drug is altered in diseased ducks due to the increased serum orbifloxacin concentrations compared with clinically healthy ducks. In conclusion, 5 mg kg⁻¹ body weight of orbifloxacin administered as a single dose once daily could be useful in the treatment of disease caused by Pasteurella multocida pathogen in ducks.

Can Uremia and Hemodialysis Affect Plasma Levels of Circulating TNF-alpha.

It is well known that uremia is associated with increased susceptibility to infection. In addition, patients on haemodialysis (HD) experience a variety of dialysis associated complications, both acute and chronic, many of them having features similar to acute phase response. Immunoregulatory cytokines such as tumor necrosis factor-a (TNF-a) have been implicated in the pathogenesis of immunological as well as inflammatory diseases. Thus, TNF-a levels could be expected to be high in uremic patients as well as in HD patients. We investigated the plasma levels of TNF-a in 17 patients with renal failure, seven patients with chronic renal failure (CRF) before commencement of HD and 10 patients maintained on regular HD. Eight age matched healthy subjects were studied as normal control. All CRF patients, who were not yet on dialysis, had high plasma levels of TNF-a (mean + SD 71.33 + 33.25 pg/ml). Out of the HD group, TNF-a plasma levels were not detectable in five patients and in the remaining five, TNF-a plasma level (mean + SD 21.06 + 7.72) were comparable to the normal controls (mean + SD 21 + 7.87). Our findings suggest that factors related to uremia, but not to HD, are responsible for high TNF-a plasma levels in these patients and that, HD probably has a beneficial effect by removal and/or neutralising of uremic toxins.