Evaluation of the clinical efficacy of racecadotril in the treatment of neonatal calves with infectious diarrhea.

Racecadotril, used as an antidiarrheal drug in humans and some animals such as the dog, inhibits peripheral enkephalinase, which degrades enkephalins and enkephalinase inhibition induces a selective increase in chloride absorption from the intestines. The study material consisted of 46 calves with infectious diarrhea and 14 healthy calves in the age 2-20 days. The calves were divided into eight groups; healthy calves (HG), healthy calves administered racecadotril (HRG), calves with E.coli-associated diarrhea (ECG), calves with E.coli-associated diarrhea administered racecadotril (ECRG), calves with bovine Rotavirus/Coronavirus-associated diarrhea (VG), calves with bovine Rotavirus/Coronavirus-associated diarrhea administered racecadotril (VRG), calves with C. parvum-associated diarrhea (CG) and calves with C. parvum-associated diarrhea administered racecadotril (CRG). Calves in the racecadotril groups received oral racecadotril at a dose of 2.5 mg/kg twice a day for 3 days. A routine clinical examination of all calves was performed. Hemogram and blood gas measurements were made from the blood samples. Standard diarrhea treatment was applied to the HG, ECG, CG, and VG groups. Clinical score parameters such as appetite, feces quality, dehydration, standing and death and some blood gas and hemogram parameters were evaluated to determine the clinical efficacy of racecadotril. Clinical score parameters were determined observationally. Blood gas measurements were performed using a blood gas analyzer. The hemogram was performed using an automated hematologic analyzer. Statistically significant differences were determined in the blood pH, bicarbonate, base deficit, lactate, and total leukocyte count in calves with diarrhea compared to healthy calves. After the treatments, these parameters were found to be within normal limits. At the end of treatment, 42 of the 46 diarrheal calves recovered, while 4 died. We found that racecadotril was effective in improving both clinical recovery and feces consistency in neonatal calves with diarrhea caused by E. coli. As a result, it can be stated that racecadotril, which has an antisecretory effect, is beneficial in the treatment of bacterial diarrhea caused by such as E. coli.

The effect of tilmicosin and diclofenac sodium combination on cardiac biomarkers in sheep.

The aim of this study was to investigate the cardiotoxic effect of the combination of tilmicosin and diclofenac sodium in sheep. Thirty-two sheep were used and were randomly divided into four equal groups as tilmicosin (T), diclofenac sodium (D), tilmicosin+diclofenac sodium (TD) and control (C) group. Group T received a single dose of tilmicosin, Group D was administered diclofenac sodium once a day for 3 days, and group TD was administered diclofenac and tilmicosin at the same doses as group T and D. Group C received NaCl in a similar way. The blood samples were taken before dosing and at 4th, 8th, 24th and 72nd hour post-dosing for measurement of cardiac markers such as H-FABP, cTn-I, CK-MB. H-FABP level of group TD was found to be significantly (p⟨0.05) higher than of group C at the 8th, 24th and 72nd hour and group D and T at the 72nd hour. cTn-I and CK-MB levels of group TD were found significantly (p⟨0.05) higher compared with other groups. In conclusion, the combined use of tilmicosin and diclofenac in sheep causes an increase in cardiac biomarkers and it can be stated that this combination of drugs may cause cardiac damage.

The effects of dexamethasone and minocycline alone and combined with N-acetylcysteine and vitamin E on serum matrix metalloproteinase-9 and coenzyme Q10 levels in aflatoxin B1 administered rats.

This study aimed to determine the effects of dexamethasone and minocycline alone and combined treatment with N-acetylcysteine (NAC) and vitamin E on serum coenzyme Q10 (CoQ10) and matrix metalloproteinase-9 (MMP-9) levels in rats administered aflatoxin B1 (AFB1). The study was carried out on 66 male Wistar rats. Following the intraperitoneal (IP) administration of AFB1 at dose of 2 mg/kg, minocycline (45 and 90 mg/kg, IP) and dexamethasone (5 and 20 mg/kg, IP) were administered alone and combined with NAC (200 mg/kg, IP) and vitamin E (600 mg/kg, IP). CoQ10 and MMP-9 levels were analyzed using the HPLC-UV method and a commercial kit by ELISA, respectively. AFB1 increased MMP-9 level and decreased CoQ10 level compared to the control group. After dexamethasone and minocycline administration, there is no increase in CoQ10 level, which is caused by AFB1. However, dexamethasone and minocycline combined with NAC+vitamin E caused significant increases in CoQ10 levels. Dexamethasone and minocycline alone and combined with NAC+vitamin E decreased MMP-9 levels compared to the single AFB1 treated group. The use of MMPs inhibitors and oxidative stress-reducing agents is anticipated to be beneficial in the poisoning with AFB1.

Serum sRAGE and sE-selectin levels are useful biomarkers of lung injury and prediction of mortality in calves with perinatal asphyxia.

The objective of the present study was to evaluate the biomarkers specific to lung endothelial and epithelial damage in the determination of lung injury and its severity in calves with perinatal asphyxia and to evaluate their prognostic importance among survivors and non-survivor calves. Ten healthy calves and 20 calves with perinatal asphyxia were enrolled in the study. Clinical examination and laboratory analysis were performed at admission. Serum concentrations of soluble advanced glycation end-product receptor (sRAGE), soluble E-selectin (sE-selectin), clara cell secretory protein (CC16), and soluble intercellular adhesion molecule-1 (sICAM-1) were measured to assess lung injury. Venous pH, sO2, HCO3, and BE of calves with perinatal asphyxia were significantly lower than the healthy calves. sRAGE, sE-selectin, pCO2, and lactate were significantly high in calves with asphyxia. ROC analysis showed that sRAGE, sE-selectin, pCO2, lactate, and respiratory rate were higher while HCO3 and BE were lower in the nonsurvivor calves than survivors. In conclusion, serum sRAGE and sE-selectin concentrations highlight the utility of these biomarkers in determining lung injury in calves with asphyxia. Also, pH, pCO2, lactate, HCO3, BE, and respiratory rate along with serum sRAGE and sE-selectin were useful indicators in the prediction of mortality.

Pharmacokinetics of intravenous meloxicam, ketoprofen and tolfenamic acid in chukar partridge (Alectoris chukar).

1. The aim of this study was to determine the pharmacokinetics of meloxicam (MLX, 1 mg/kg body weight (BW)), ketoprofen (KETO, 2 mg/kg BW), and tolfenamic acid (TA, 2 mg/kg BW) in chukar partridge (Alectoris chukar) following intravenous (IV) administration.2. Twenty-four healthy chukar partridges were randomly divided into three equal groups (n = 8) as MLX, KETO and TA. Plasma concentrations of MLX, KETO and TA were measured using high-performance liquid chromatography-ultraviolet detection and analysed using non-compartmental analysis.3. No adverse effects were determined in chukar partridges after IV administration of MLX, KETO and TA. MLX, KETO and TA were detected in plasma up to 10, 12 and 12 h, respectively. The terminal elimination half-life of MLX, KETO and TA was 1.22, 1.77 and 1.95 h, respectively. MLX, KETO and TA exhibited volumes of distribution at a steady-state of 0.03, 0.23 and 0.41 l/kg BW, respectively. The total plasma clearance of MLX, KETO and TA was 0.02, 0.11 and 0.15 l/h/kg, respectively. The extraction ratios for MLX, KETO and TA were calculated as 0.002, 0.011 and 0.016, respectively.4. MLX, KETO and TA offer treatment in chukar partridges for various conditions with an absence of adverse reactions and properties such as short elimination half-life and low volume of distribution. However, there is a need to establish the safety and adverse effects of repeated administration, pharmacokinetics of other administration routes and pharmacological efficacy of MLX, KETO and TA in chukar partridges.

Distribution of hydrophilic and lipophilic antibacterial drugs in skim milk, cream, and casein.

This study determined the distribution of drugs to different milk fractions according to their physicochemical properties. Hydrophilic drugs tend to concentrate in skim milk, whereas lipophilic drugs tend to concentrate in cream. The concentration of a drug in casein is related to its degree of binding to milk proteins. Thus, we aimed to determine whether withdrawal time in whole milk differs from that in cream, casein, and skim milk. Amoxicillin and tylosin were selected as prototype hydrophilic and lipophilic drugs, respectively. The study was conducted in vitro and in vivo to determine whether in vitro conditions reflect the distribution of drugs in the different milk fractions in vivo. The in vivo study was conducted using a crossover design on 6 healthy Holstein dairy cattle. First, amoxicillin (i.m., single dose, 14 mg/kg) was administered to cows. Following a 1-wk washout period, tylosin (i.m., single dose, 15 mg/kg) was administered. Concentrations of amoxicillin and tylosin in milk and milk fractions were measured using HPLC-UV. In the in vitro study, 0.04 to 400 µg/g of amoxicillin and 0.05 to 50 µg/g of tylosin were spiked to drug-free milk and the concentrations in milk and milk fractions were measured. In addition, the percentage of total protein in milk and milk fractions was determined. Amoxicillin accumulated more in skim milk than in cream and casein, both in vitro (92%) and in vivo (73%, skim milk-to-whole milk ratio). The distribution of tylosin in whole and skim milk was similar to that of amoxicillin in the in vitro study, in contrast to the accumulation of tylosin in cream seen in vivo. However, the accumulation ratio of tylosin in cream was lower than expected. By either method, tylosin was less concentrated in casein than in skim milk and cream. The percentage of total protein was similar in skim milk and whole milk and higher than in cream. Thus, amoxicillin accumulates less in cream and casein, suggesting that these fractions would pose a lower risk to the consumer. Tylosin was still present at the maximum residue limit (50 µg/kg) 24 h after injection in the casein fraction and 48 h after injection in the cream fraction.

Pharmacokinetics of cefquinome in red-eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections.

The purpose of this study was to evaluate the pharmacokinetics of cefquinome (CFQ) following single intravenous (IV) or intramuscular (IM) injections of 2 mg/kg body weight in red-eared slider turtles. Plasma concentrations of CFQ were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. The pharmacokinetic parameters following IV injection were as follows: elimination half-life (t1/2λz ) 21.73 ± 4.95 hr, volume of distribution at steady-state (Vdss ) 0.37 ± 0.11 L/kg, area under the plasma concentration-time curve (AUC0-∞ ) 163 ± 32 µg hr-1  ml-1 , and total body clearance (ClT ) 12.66 ± 2.51 ml hr-1  kg-1 . The pharmacokinetic parameters after IM injection were as follows: peak plasma concentration (Cmax ) 3.94 ± 0.84 µg/ml, time to peak concentration (Tmax ) 3 hr, t1/2λz 26.90 ± 4.33 hr, and AUC0-∞ 145 ± 48 µg hr-1  ml-1 . The bioavailability after IM injection was 88%. Data suggest that CFQ has a favorable pharmacokinetic profile with a long half-life and a high bioavailability in red-eared slider turtles. Further studies are needed to establish a multiple dosage regimen and evaluate clinical efficacy.

Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses.

The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2-amino-5-thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high-performance liquid chromatography assay. The data were evaluated using noncompartmental pharmacokinetic analyses. The estimated plasma pharmacokinetic parameters were compared with the hypothetical minimum inhibitory concentration (MIC) values (0.125-2 µg/mL). The plasma and synovial fluid concentrations and area under the concentration-time curves (AUC) of cefquinome showed a dose-dependent increase. After a first dose of cefquinome, the ranges for the mean plasma half-life values (2.30-2.41 h), the mean residence time (1.77-2.25 h), the systemic clearance (158-241 mL/h/kg), and the volume of distribution at steady-state (355-431 mL/kg) were consistent across dose levels and similar to those observed after multiple doses. Cefquinome did not accumulate after multiple doses. Cefquinome penetrated the synovial fluid with AUCsynovial fluid /AUCplasma ratios ranging from 0.57 to 1.37 after first and thirteenth doses, respectively. Cefquinome is well tolerated, with no adverse effects. The percentage of time for which the plasma concentrations were above the MIC was >45% for bacteria, with MIC values of ≤0.25, ≤0.5, and ≤1 µg/mL after the administration of 1, 2, and 4 or 6 mg/kg doses of CFQ at 12-h intervals, respectively. Further studies are needed to determine the optimal dosage regimes in critically ill patients.

Protective effect of distillated Nerium oleander on heart of type 2 diabetic rats.

OBJECTIVES: The current study aims to investigate the possible role of NO distillate either for therapeutic or for protective potential in diabetic cardiomyopathy. BACKGROUND: Protective and restorative effects of distillated Nerium oleander (NO) on the diabetes-induced electrophysiological and structural alterations were investigated. METHODS: Type 2 diabetes was induced by combination of single dose streptozotocin injection and high fat diet for four weeks. Experimental groups were designed as follows: control, diabetic, restorative-NO treated diabetic and protective-NO treated diabetic. Intracellular action potentials (AP) and contractile activities were measured form left ventricular papillary muscle strips as well as histopathological examination of heart tissue and biochemical examinations of serum were performed. RESULTS: Type 2 diabetes induced AP prolongation was prevented with both ways of NO treatments. Moreover, treatments produced nearly complete restorations of diabetes-induced depressed amplitude and altered kinetics of contractile activities. In parallel to electrophysiological parameters, both histopathological and biochemical results indicates the NO induced beneficial effects on the diabetes related alterations. CONCLUSION: Distillated Nerium oleander (NO) can be a highly potential therapeutic or preventive agent on the diabetes induced excitation-contraction coupling alterations (Tab. 3, Fig. 3, Ref. 23).

Bioavailability and pharmacokinetic profile of levofloxacin following intravenous, intramuscular and oral administration in turkeys.

1. The pharmacokinetics and bioavailability of levofloxacin in turkeys were investigated after a single intravenous (IV), intramuscular (IM) and oral (PO) administration of 10 mg/kg body weight. 2. The concentrations of levofloxacin in plasma samples were assayed using a microbiological assay method and pharmacokinetic parameters were calculated by non-compartmental analysis. 3. Following IV administration, the elimination half-life (t0.5(ß)), volume of distribution at steady state (Vdss) and total body clearance (Cl) were 4.49 h, 1.31 l/kg and 0.23 l/h/kg, respectively. 4. After single IM and PO administrations at the same dose, levofloxacin was rapidly absorbed as indicated by an absorption half-life (t0.5ab) of 1.02 and 0.76 h, respectively; maximum plasma concentrations (Cmax) of 5.59 and 5.15 µg/ml were obtained at a maximum time (Tmax) of 2 h for both routes and levofloxacin bioavailability (F) was 96.5 h and 79.9% respectively after IM and PO administration. In vitro plasma protein binding of levofloxacin was 24.3%. 5. Based on these pharmacokinetic parameters, a dose of 10 mg/kg body weight given intramuscularly or orally every 24 h in turkeys can maintain effective plasma concentrations with bacterial infections with (minimum inhibitory concentration) MIC90 > 0.1 µg/ml.

Effect of zinc supplementation on lipid peroxidation and lactate levels in rats with diabetes induced by streptozotocin and subjected to acute swimming exercise.

OBJECTIVE: The present study aims to explore the effect of zinc supplementation on lipid peroxidation and lactate levels in rats having diabetes induced by streptozotocin and subjected to acute swimming exercise. METHOD: A total of 80 adult male rats of Sprague-Dawley type were equally allocated to 8 groups: Group 1, general control. Group 2, zinc-supplemented group. Group 3, zinc-supplemented, diabetic group. Group 4, swimming control group. Group 5, zinc-supplemented swimming group. Group 6, zinc-supplemented diabetic swimming group. Group 7, diabetic swimming group. Group 8, diabetic group. At the end of the 4-week study, blood samples were collected to determine MDA, GSH, GPx, SOD, lactate and zinc levels. RESULTS: The highest MDA values were found in group 7 and 8 (p<0.001). GSH values in groups 5 and 6 were higher (p<0.001). The highest GPx values were established in groups 2, 5 and 6 (p<0.001). SOD values were the highest in groups 5 and 6 (p<0.001) and lowest in groups 2, 3 and 8 (p<0.001). The highest plasma lactate levels were found in group 7 (p<0.001). The highest zinc levels were obtained in groups 1, 2 and 5 (p<0.001), and the lowest zinc levels were found in groups 7 and 8 (p<0.001). CONCLUSION: Results of the study reveal that zinc supplementation prevents the increase of free radical formation, suppression of antioxidant activity and muscle exhaustion, all of which result from diabetes and acute exercise. Zinc supplementation may contribute to health performance in diabetes and acute exercise (Tab. 2, Fig. 1 Ref. 47). Full Text in PDF www.elis.sk.

Pharmacokinetics of florfenicol in the plasma of Japanese quail.

AIM: To determine the pharmacokinetics and bioavailability of florfenicol in the plasma of healthy Japanese quail (Coturnix japonica). METHODS: Sixty-five quail were given an I/V and I/M dose of florfenicol at 30 mg/kg bodyweight (BW). A two-period sequential design was used, with a wash-out period of 2 weeks between the different routes of administration. Concentrations of florfenicol in plasma were determined using high-performance liquid chromatography (HPLC). RESULTS: A naïve pooled data analysis approach for the plasma concentration-time profile of florfenicol was found to fit a non-compartmental open model. After I/V administration, the mean residence time (MRT), mean volume of distribution at steady state (Vss), and total body clearance of florfenicol were 12.0 (SD 0.37) h, 8.7 (SD 0.22) L/kg, and 1.3 (SD 0.08) L/h/ kg, respectively. After I/M injection, the MRT, mean absorption time (MAT), and bioavailability were 12.3 (SD 0.37) h, 0.2 (SD 0.02) h, and 79.1 (SD 1.79)%, respectively. CONCLUSIONS: The time for the concentration of florfenicol to fall below the probable effective concentration of 1 microg/ ml of approximately 10 h is sufficient for the minimum inhibitory concentration needed for many bacterial isolates. Further pharmacodynamic studies in quail are needed to evaluate a suitable dosage regimen.

Effect of flunixin meglumine on cytokine levels in experimental endotoxemia in mice.

In this study, effect of flunixin meglumine on serum tumour necrosis factor alpha, (TNFalpha) interleukin-1 beta and interleukin-10 levels was investigated in lipopolysaccharide-induced endotoxic mice. Healthy 273 Balb/C mice were used and divided into three equal groups. Group 1 was injected lipopolysaccharide (Escherichia coli 0111:B4, 250 microg/mouse, intraperitoneally), Group 2 was injected flunixin meglumine (2.5 mg/kg, subcutaneously), and Group 3 was injected lipopolysaccharide + flunixin meglumine. After the treatments, at 0., 1., 2., 3., 6., 12., 24th hours and 3., 5., 7., 14., 21., 28th days blood samples were taken from seven mice in each group. Serum TNFalpha, interleukin-1 beta and interleukin-10 levels were measured using commercially available kits by enzyme-linked immunoassay. Flunixin meglumine did not affect the cytokine levels in healthy animals. While lipopolysaccharide increased serum TNFalpha, interleukin-1 beta and interleukin-10 levels, flunixin meglumine inhibited increases at levels of all cytokines. As result, flunixin meglumine showed depressor effect on cytokine levels in endotoxemia and the effect may be a reason for the first chosen member of nonsteroid anti-inflammatory drug in endotoxemia.

Influence of Escherichia coli endotoxin-induced endotoxaemia on the pharmacokinetics of enrofloxacin after intravenous administration in rabbits.

The main goal of present study was to determine the effects of an Escherichia coli endotoxin-induced endotoxaemic status on disposition of enrofloxacin after a single intravenous dose (5 mg/kg) in rabbits. Septic shock was induced by the i.v. bolus administration at a single dose of E. coli lipopolysaccharide. Six adult New Zealand White rabbits were used. Concentrations of drug in plasma were determined by HPLC. The plasma pharmacokinetic values for enrofloxacin were best represented using a two-compartment open model. Total plasma clearance (Cl(T)) decreased from 2.11 (l/h/kg) in healthy animals to 1.50 (l/h/kg) in rabbits with septic shock, which is related to an increase in the AUC(0-->infinity). In endotoxaemic rabbits, volume of distribution at steady state (V(dss) = 3.61 l/kg) was significantly lower (P < 0.05) than in healthy animals (V(dss) = 4.97 l/kg). However, the elimination half-life of enrofloxacin was not affected by lipopolysaccharide administration.

Pharmacokinetics of flunixin after intravenous administration in healthy and endotoxaemic rabbits.

The pharmacokinetics of flunixin were determined after intravenous bolus injection at a single dose (2.2 mg/kg) in healthy rabbits and diseased rabbits with Escherichia coli lipopolysaccharide-induced septic shock. Six adult New Zealand White rabbits were used. Concentrations of drug in plasma were determined by HPLC. Pharmacokinetics were best described by a two-compartment open model. In healthy rabbits, there was a high plasma clearance (0.62 L/(h kg)), and a relatively short elimination half-life (1.19 h). In endotoxaemic rabbits, total plasma clearance (0.43 L/(h kg)) was significantly lower (p<0.05), and elimination half-life (1.90 h) and AUC(0-infinity) (5.29 (microg h)/ml) were significantly higher (p<0.05) than in healthy animals. The changes of pharmacokinetics of flunixin in rabbits with septic shock could be of clinical significance, and may require monitoring of plasma flunixin levels in endotoxaemic status.