Disposition Kinetics of Difloxacin After Intravenous,Intramuscular and Subcutaneous Administration in Calves

The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study using three groups (n = 4) of male and female Friesian calves after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg body weight. Drug concentration in plasma was determined by high-performance liquid chromatography using fluorescence detection. The plasma concentration–time data following i.v. administration were best fitted to a two-compartment open model and those following i.m. and s.c. routes were best fitted using one-compartment open model. The collected data were subjected to a computerized kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives (t _1/2β) were 5.56 ± 0.33 h, 6.12 ± 0.42 h and 7.26 ± 0.6 h, respectively. The steady-state volume of distribution (V _dss) was 1.12 ± 0.09 L/kg and total body clearance (Cl_B) was 2.19 ± 0.1 ml/(min. kg). The absorption half lives (t _1/2ab) were 0.38 ± 0.027 h and 2.1 ± 0.09 h, with systemic bioavailabilities (F) of 96.5% ± 6.4% and 84% ± 5.5% after i.m. and s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma concentrations (C _max) of 3.38 ± 0.13 μg/ml and 2.18 ± 0.12 μg/ml were attained after (t _max) 1.22 ± 0.20 h and 3.7 ± 0.52 h. The MIC₉₀ of difloxacin for Mannheimia haemolytica was 0.29 ± 0.04 μg/ml. The AUC/MIC₉₀ and C _max/MIC₉₀ ratios for difloxacin following i.m. administration were 120 and 11.65, respectively and following s.c. administration were 97.58 and 7.51, respectively. Difloxacin was 31.7–36.8% bound to calf plasma protein. Since fluoroquinolones display concentration-dependent activities, the doses of difloxacin used in this study are likely to involve better pharmacodynamic characteristics that are associated with greater clinical efficacy following i.m. administration than following s.c. administration.     

Synovial fluid analysis and bacterial findings in arthritic joints of juvenile male camel (Camelus dromedarius) calves

Eighteen synovial fluid samples from 11 male dromedarian calves, 9-12 month old, were analysed cytologically and bacteriologically. Calves were lame and all joints were grossly swollen. The mean +/- SD of total nucleated cell count was 7970 +/- 5000 cells/microl (range 2800-20,000 cells/microl). Polymorphonuclear (PMN) leucocytes were the predominant cell type. The mean +/- SD of absolute and percentages of each cell type were as follows: PMN leucocytes 5518 +/- 3600 cells/microl and 68 +/- 19%, monocytes/macrophages 1600 +/- 1120 cells/microl and 26 +/- 17%, lymphocytes 830 +/- 140 cells/microl and 8 +/- 7%, and red blood cell 350 +/- 130 cells/microl. The mean +/- SD of total protein concentration was 3.5 +/- 1 g/dl (range 2.5-5 g/dl). The most commonly isolated bacteria were non-haemolytic streptococci spp., followed by Arcanobacterium pyogenes and Staphylococcus aureus. No bacterial growth was obtained in eight samples and non-revealed Mycoplasma spp.     

Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves

The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.     

Dihydrooxadiazines: Octopaminergic system as a potential site of insecticidal action

Dihydrooxadiazines are structural analogs of octopamine and were compared with octopamine for their ability to compete with [³H]dihydroergocryptine ([³H]DHE) for binding sites on DHE-sensitive receptors, to stimulate adenylate cyclase activity in nervous system homogenates of Periplaneta americana L., and to modulate the action of the peptide proctolin on the oviducal muscles of Locusta migratoria L. [³H]DHE binding was inhibited by low concentrations (μM range) of octopamine, phentolamine, N-demethylchlordimeform (DCDM) and several dihydrooxadiazines. The tested dihydrooxadiazines acted as aminergic agonists in stimulating cyclic AMP production in cockroach nervous system homogenates and did not show additive effects with octopamine, whereas additivity was observed with 5-hydroxytryptamine. The relative potency of octopaminergic antagonists, including mianserin, cyproheptadine, phentolamine, and gramine, to block octopamine-mediated elevation of cyclic AMP production was similar to the rank-order potency of the same antagonists to inhibit dihydrooxadiazine-mediated elevation of cyclic AMP production. Octopamine, 2-(4-bromophenyl)-5,6-dihydro-4H-1,3,4-oxadiazine (4-Br-PDHO), and 8-Br-cyclic AMP caused increased phosphorylation of proteins that are phosphorylated by exogenously added cyclic AMP-dependent protein kinase. These results indicate that the dihydrooxadiazine-induced rise in cyclic AMP levels in homogenates of the cockroach nervous system results directly in activation of an endogenous cyclic AMP-dependent protein kinase. 4-Br-PDHO behaved similarly to octopamine in modulating the action of proctolin-induced contractions in locust oviducal muscles. These observations suggest that dihydrooxadiazines act as octopamine agonists and have an octopaminergic action in modulating the action of proctolin. Thus, it is proposed that dihydrooxadiazines exert at least part of their insecticidal and miticidal actions through interaction with the octopaminergic system.     

Pathogenicity of peste des petits ruminants virus isolated from Egyptian goats in Egypt

2 Egyptian goats and Boscat rabbits were experimentally inoculated with peste des petits ruminants (PPR) local Egyptian strain (PPR, Egypt 87). The inoculated animals contracted the disease with minor clinical manifestations, accompanied by rise of neutralizing antibodies to PPR virus. Virus was isolated from ocular and nasal secretions, buffy coat, spleen, and liver. No contact infection was observed between inoculated and healthy goats.     

Geometry of the femoral condyles in dogs

The stifle joint is one of the most important joints in dogs from the orthopaedic point of view. The aim of this study was to document the morphometric values of femoral condyles, given the close relationship between the shape and function of an anatomic structure. The left femora of 16 mid-sized dogs were used, and diameter and nine radii as well as cranial and caudal bow lengths from each condyle were measured. The photographs were taken of the distal femora from both sides. All measurements were obtained from these images by using software. Additionally, the rotation angle was calculated from the intercondylar distance and the difference between lateral and medial bow lengths. In addition to the rotation angle, the difference of diameter and nine radii between the lateral and medial condyles was determined. All radii except getting at 90° were significantly different between the medial and lateral condyles. The greatest values were determined in the caudal part of the medial condyle. This results the smaller contact area and a greater pressure on the underlying surface, and therefore the meniscus and articular cartilage of the caudal part of the medial side suggests the possibility of a risk of injury as the stifle joint flexes. The mean rotational angle of the femur was also calculated to be 2.18° laterally and 1.02° medially in the caudal and cranial parts of condyles, respectively. The result of this study showed that the lateral and medial condyles had different shapes in canine femur.     

Ultrasonographic examination of the carpal canal in dogs

The aim of this study was to determine the course of the median nerve and its adjacent structures in the carpal canals of 8 healthy dogs by using high-frequency transducers. Before performing ultrasonography, the transverse and posteroanterior diameters as well as the perimeter of the carpus were measured at just proximal to the side of the carpal pad. The anatomical structures were then determined at two levels of the carpal canal, which were named the proximal and distal levels, on the transverse sonograms. The cross-sectional areas, perimeters and the transverse and posteroanterior diameters of the median nerve were measured at these levels. Although all the measurements were larger at the proximal level, significant differences between the proximal and distal levels were determined for the cross-sectional area, the perimeter and the transverse diameter of the median nerve. On the transverse sonogram, the deep digital flexor tendon was seen in almost the center of the carpal canal like a comma shape and also it had a small concavity on the caudal side. The superficial digital flexor tendon was seen as an ovoid shape on the transverse sonograms and it was located nearly at the posterior side of the carpal canal. Both tendons were seen as intermediate-grade echogenic structures. The median artery was located inside of the concavity of the deep digital flexor tendon. Also, the median nerve was seen at the posteromedial side of the median artery. As a result of this study, the cross-sectional areas of the median nerve ranged between 1.01-2.68 mm² at the proximal level and between 0.93-1.91 mm² at the distal level.     

Comparison of pregnancy per AI of heifers inseminated with sex-sorted or conventional semen after oestrus detection or timed artificial insemination

The objective of the study was to compare the fertility after using sex-sorted or conventional semen either with oestrus detection (EST) or timed artificial insemination (TAI) in Holstein heifers. Holstein heifers were randomly assigned to one of the following treatments in a 2 × 2 factorial design. Heifers in the EST group were inseminated with sex-sorted (n = 114) or conventional semen (n = 100) after spontaneous or induced oestrus. Heifers in the TAI, subjected to the 5-day Cosynch+Progesterone protocol (GnRH+P4 insertion-5d-PGF_2α+P4 removal-1d-PGF_2α-2d-GnRH+TAI), were inseminated with sex-sorted (n = 113) or conventional semen (n = 88). Statistical analyses were performed using PROC GLIMMIX procedure of SAS 9.4 (SAS Institute Inc., Cary, NC). Overall P/AI was 60.7% for EST and 54.2% for TAI regardless of types of semen and 68.1% for conventional and 48.9% for sex-sorted semen regardless of insemination strategies. Fertility of heifers inseminated with either sex-sorted (53.5%; 44.2%) or conventional (69.0%; 67.0%) semen did not differ between EST and TAI respectively. Besides, the interaction between the semen type and the insemination strategy was not significant for P/AI. The embryonic loss was significantly greater with sex-sorted semen (17.1%) compared to conventional semen (1.6%). There was no sire effect with sex-sorted semen on P/AI (52.6% vs. 46.2%) and embryonic loss (16.4% vs. 18.0%). As expected, sex-sorted semen resulted in more female calves (89.8% vs. 51.6%) than conventional semen. Thus, sex-sorted semen can be used with 5-day Cosynch+Progesterone protocol to eliminate the inadequate oestrus detection and to increase female calves born in dairy heifers.