Comparison of pharmacokinetics of two tylvalosin oral formulations in broiler chickens.

The objective of the study was to compare the relative bioavailability and pharmacokinetics of two commercially available oral formulations of tylvalosin prepared for use in broiler chickens (ProviLosinR and AviLosinR ). A total of 36 healthy, broiler chickens were administered a single oral dose (25 mg/kg b.w.) of each formulation in a parallel randomized design. The relative bioavailability of ProviLosinR was 108% compared to AviLosinR . There were no significant differences between ProviLosinR and AviLosinR tylvalosin formulations in the average means of the area under the plasma concentration-time curve, maximum plasma concentrations and time to maximum plasma concentrations. In conclusion, tylvalosin was rapidly absorbed and relatively slowly eliminated after oral administration of a single dose for both formulations. ProviLosinR and AviLosinR can be used interchangeably as therapeutic agents in broiler chickens.

Congenital abnormalities in dead-in-shell chicks associated with mixed bacterial infections.

Determination of the chick embryonic developmental period at which embryonic mortalities occur could help in establishing the cause of such mortalities. The late stage of embryonic development has particular importance due to its dramatic effect on life after hatching. This study was conducted to investigate the occurrence, frequency and bacterial isolates from dead-in-shell chick embryos in Northern Jordan. A total of 1,000 unhatched eggs were collected at hatching day from 10 hatcheries located in Northern Jordan. Out of 1,000 eggs, 357 (35.7%) were fertile, of which 210 (58.8%) were dead-in-shell embryos. Approximately 50.5% of the dead embryos displayed abnormalities, including neck muscles with subcutaneous petechial haemorrhages (44.3%), beak abnormalities (3.8%), eye deformities (1.9%) and anencephaly (0.5%). Sixty-six bacterial isolates were identified from 82 samples from the dead-in-shell embryos. The isolates were 22 (33.3%) Escherichia coli, 18 (27.3%) Klebsiella pneumoniae, 14 (21.2%) Staphylococcus aureus, 5 (7.6%) Pseudomonas aeruginosa, 4 (6.1%) Salmonella enteritidis, 2 (3%) Bacillus cereus and 1 (1.5%) Proteus vulgaris. Mixed growth was also recorded in 16 (19.5%) samples. There was a significant (P < 0.05) association between Escherichia coli as a bacterial isolate and the occurrence of neck and beak abnormalities. In this study, infection of check embryos with several bacterial species, particularly Escherichia coli, was identified as an important cause of multiple congenital abnormalities involving the neck and beak of unhatched chicks.

Pharmacokinetics and bioavailability of tildipirosin following intravenous and subcutaneous administration in horses.

This study was designed to investigate the safety and pharmacokinetic (PK) profile of tildipirosin in horses after intravenous (i.v.) and subcutaneous (s.c.) injection of a single dose at 4 mg/kg of body weight (b.w.). A total of 12 healthy mixed breed horses were used in the study. Horses were monitored for systemic and local adverse effects, and whole blood samples were collected for hematology and plasma biochemistry analysis at time (0) and at 6, 24, and 72 h after drug administration. For PK analysis, blood samples were collected at pre-determined times before and after tildipirosin administration. Plasma concentrations of tildipirosin were determined using ultra-high-performance liquid chromatography-ultraviolet detection method (UHPLC-UV). All horses tolerated the i.v. injection of tildipirosin without showing any systemic adverse effects. However, a non-painful, soft swelling appeared at the s.c. injection site in 5 horses (41.7%). On average, tildipirosin reached a maximum plasma concentration (Cmax ) of 1257 ng/ml (geometric mean) between 0.5 and 1.5 h after s.c. administration (Tmax ). The geometric mean values for total body clearance (Cl), the apparent volume of distribution based on the terminal phase (Vz ), and the apparent volume of distribution at steady-state (Vss ) were 0.52 L/kg·h, 22 L/kg, and 10.0 L/kg, respectively. Data collected in this study suggests that tildipirosin can be used safely in horses with caution.

Pharmacokinetics and bioavailability of tildipirosin following intravenous and subcutaneous administration in sheep.

Tildipirosin is a semi-synthetic macrolide antibiotic commonly used in cattle and swine to treat bacterial pneumonia. The objective of this study was to investigate the pharmacokinetic profile of tildipirosin after a single intravenous (i.v.) and subcutaneous (s.c.) administration in healthy lambs. Eighteen lambs were randomly divided into three groups (n = 6 each). Lambs received a single s.c. dose of tildipirosin at 4 and 6 mg/kg b.w. in group 1 and 2, respectively. Lambs in group 3 received a single i.v. dose of tildipirosin at 4 mg/kg b.w. Blood samples were collected at 0, 0.5, 0.75, 1.5, 2, 3, 4, 6, 8, 10, 24, 36, 48 hr, and every 24 hr to day 21, and thereafter at day 28 posttildipirosin administration. The plasma concentrations of tildipirosin were determined using high-performance liquid chromatography with tandem mass spectrometry detection (LC/MS/MS). All lambs appeared to tolerate both the intravenous and subcutaneous injection of tildipirosin. Following i.v. administration, the elimination half-life (T1/2 ), mean residence time (MRT), volume of distribution (Vd/F), and total body clearance (Cl/F) were 119.6 ± 9.0 hr, 281.9 ± 25.7 hr, 521.1 ± 107.2 L, and 2.9 ± 0.5 L/hr, respectively. No significant differences in Cmax (657.0 ± 142.8 and 754.6 ± 227.1 ng/ml), Tmax (1.21 ± 0.38 and 1.35 ± 0.44 hr), T1/2 (144 ± 17.5, 156.5 ± 33.4 hr), and MRT (262.0 ± 30.2 and 250.6 ± 54.5 hr) were found in tildipirosin after s.c. dosing at 4 and 6 mg/kg b.w., respectively. The absolute bioavailability (F) of tildipirosin was 71.5% and 75.3% after s.c. administration of 4 and 6 mg/kg b.w., respectively. In conclusion, tildipirosin was rapidly absorbed and slowly eliminated after a single s.c. administration in healthy lambs. Tildipirosin could be used for the treatment and prevention of respiratory bacterial infections in sheep. However, further in vitro and in vivo studies to determine the efficacy and safety are warranted. To our knowledge, this is the first study to determine the tildipirosin pharmacokinetic parameters in sheep plasma.

Peripheral nerve regeneration: A comparative study of the effects of autologous bone marrow-derived mesenchymal stem cells, platelet-rich plasma, and lateral saphenous vein graft as a conduit in a dog model.

BACKGROUND: The quality of healing of peripheral nerve injuries remains a common challenge causing pain and poor quality of life for millions of people and animals annually. AIMS: The objectives of this study were to evaluate the healing quality of facial nerve injury in a dog model following local treatment using an autologous injection of platelet-rich plasma (PRP) or bone marrow-derived mesenchymal stem cells (BM-MSCs) at the injury site in combination with the application of an autologous saphenous vein graft as a conduit. METHODS: 20 apparently healthy adult Mongrel dogs were randomly divided into 4 equal groups. Dogs in groups 1, 2, and 3 were subjected to facial nerve neurectomy and saphenous vein conduit graft implantation at the site of facial nerve injury. Dogs in groups 2 and 3 received 1 ml of autologous PRP and BM-MSCs, respectively. Injections were administered directly in the vein conduit immediately after nerve injury. Dogs in group 1 (grafted but not treated; control) received only an autologous vein graft, and those in group 4 (normal control) received no graft and no PRP or BM-MSCs treatment. The dogs were monitored daily for 8 weeks after surgery. Clinical evaluation of the facial nerve, including lower eyelid, ear drooping, upper lip, and tongue functions, was carried out once per week using a numerical scoring system of 0-3. At the end of the study period (week 8), the facial nerve injury site was evaluated grossly for the presence of adhesions using a numerical scoring system of 0-3. The facial nerve injury site was histopathologically assessed for the existence of perivascular mononuclear cell infiltration, fibrous tissue deposition, and axonal injury using H&E-stained tissue sections. RESULTS: Clinically, BM-MSCs treated dogs experienced significant (p < 0.05) improvement in the lower eyelid, ear, lip, and tongue functions 4 weeks postoperatively compared to other groups. Grossly, the facial nerve graft site in the BM-MSCs treated group showed significantly (p < 0.05) lesser adhesion scores than the other groups. Histopathologically, there was significantly (p < 0.05) less perivascular mononuclear cell infiltration, less collagen deposition, and more normal axons at the facial nerve injury site in the BM-MSCs treated group compared to the other groups. CONCLUSION: This study showed clinically significant enhancement of nerve regeneration by applying autologous BM-MSCs and autologous vein grafting at the site of facial nerve injury. However, further clinical trials are warranted before this application can be recommended to treat traumatic nerve injuries in the field.

Occurrence of on-farm risk factors and health effects of mycotoxins in dairy farms in Jordan.

The aim of this study was to determine the occurrence of on-farm risk factors and health effects associated with contamination of dairy feeds with aflatoxins (AFs), zearalenone (ZEN), trichothecenes (T-2), deoxynivalenol (DON), and fumonisins (FB) in Jordan. A pre-tested and validated questionnaire was used to determine on-farm practices and health effects associated with high levels of mycotoxins. A total of 88 feed samples were collected from the 37 farms participating in the study and analyzed using commercially available ELISA kits. The mean total AF concentration exceeded the European Union (EU) limit in alfalfa (4%) and total mixed ration (TMR) (3%) samples. Similarly, levels exceeding EU limits were observed for T-2 in alfalfa (29%), TMR (30%), and corn silage (4%). The average concentrations of ZEN and FB were 300 ppb and 11,638 ppb, respectively, which were below the EU maximum limits in all feed samples examined. Intensive management system (OR = 7.70), imported feed (OR = 3.40), feed storage on the farm for more than 1-month duration (OR = 7.90), and not using antitoxins (OR = 2.30) were significantly (P < 0.05) associated with high levels of mycotoxins in feed samples. A significant correlation (P < 0.05) was evident between the presence of mycotoxins in dairy feed and feed refusal (R = 0.70), low milk production (R = 0.50), diarrhea problems (R = 0.60), infertility (R = 0.50), and repeated breeder problems (R = 0.80). Results show that mycotoxin contamination in dairy feeds is a problem in Jordan, and appropriate measures need to be undertaken to reduce risks to human and animal health and improve production.

Pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes and determination of their concentrations in milk, allantoic fluid, and newborn plasma.

The objectives of this study were to determine the pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes following a single oral dose and to determine the plasma concentrations of these compounds in milk, allantoic fluid, and newborn plasma. Eighteen healthy ewes were randomly divided into three groups (n = 6 each): pregnant ewes at 12-13 weeks of gestation (group A), nonpregnant ewes (group B), and pregnant ewes at 1-2 weeks before expected lambing date (group C). Ewes in all groups received a single oral dose of toltrazuril at 20 mg/kg body weight. In groups A and B, blood samples were collected at 1, 3, 5, 7, 9, 12, 15, 18 hr, every 6 hr to day 3, every 12 hr to day 7 and thereafter every 24 hr to day 14 post-toltrazuril administration. In group C, parturition was induced 24-36 hr after toltrazuril administration then milk, allantoic fluid, and newborn plasma samples were collected immediately after birth. Drug metabolites were assayed using ultra high-performance liquid chromatography-ultraviolet detection method (UHPLC-UV). The maximum concentration (Cmax ), area under the plasma concentration-time curve (AUC0-t) , AUC to 24 and 48 hr (AUC0-24 ), and (AUC0-48 ) were significantly higher in pregnant ewes. Longer apparent half-life (T1/2 ), significantly higher apparent volume of distribution (Vd/F) and total clearance (Cl/F) were observed in nonpregnant ewes. The time to maximum plasma concentration (Tmax ), mean residence time (MRT) and elimination rate constant (Kel ) were similar in both groups. The AUC0-24 and AUC0-48 were significantly higher in nonpregnant ewes. The AUC0-t was significantly higher in pregnant ones. The ratio of plasma toltrazuril concentrations in ewes and toltrazuril concentrations in newborn lambs' plasma, allantoic fluid, and milk were 68%, 2.3%, and 5.3%, respectively. Results of this study showed that toltrazuril is well absorbed after a single oral dose in ewes with widespread distribution in different body tissues.

First detection of foot-and-mouth disease virus O/ME-SA/ Ind2001e sublineage in Jordan.

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease that is caused by the FMD virus (FMDV). This disease affects both wild and domestic cloven-hoofed animals, and the latter of which includes cattle, swine, sheep and goats. FMD is endemic to Jordan and has a severe impact on the productivity of domestic livestock. In January 2017, FMD outbreaks were detected in different animal species across Jordan, resulting in high mortality rates among young lamb and goat populations as well as causing classic FMD symptoms in cattle. In this study, clinical specimens were collected from animals affected by FMD. The results obtained from sequencing the VP1 gene place the studied FMDV isolate within the FMDV O/ME-SA/ Ind2001e sublineage. Phylogenetic analysis of VP1 suggests that the O/JOR/1/2017 isolate is very similar to that of viruses isolated from Saudi Arabia in 2016. The possible introduction of this strain to Jordan might occur through transboundary animal movement or other transmission routes from Saudi Arabia, a neighbouring country.

Cardiac myxoma: clinical characteristics, surgical intervention, intra-operative challenges and outcome.

OBJECTIVE: The objectives of this retrospective study were to characterize the clinical presentation, diagnostic findings, surgical approaches, intra-operative challenges and complications following the surgical treatment of cardiac myxoma in two of the largest referral hospitals in Jordan. METHODS: Medical records of all patients presented to the cardiology department during the period between 1984 and 2016 were reviewed. Criteria for inclusion in the study were: (1) patients who were presented for cardiac evaluation due to symptoms suggestive of a primary cardiac problem, (2) completed medical records, including results of echocardiography suggestive of intra-cardiac occupying mass, (3) the surgical operation was undertaken and intra-operative data was available, (4) a histological diagnosis of myxoma was available and (5) the discharge status and follow-up data were available for at least 2 years after initial surgery. RESULTS: A total of 27 patients fulfilled the criteria for inclusion in the study. The average age was 42 years. Thirteen of the patients were females and 14 patients were males. The most common clinical presentations were dyspnea (29.6%) and murmurs (22.2%). Non-specific signs, such as weight loss, fever, fatigue, arthralgia and anemia, were reported in 10 (37%) patients. Signs related to systemic embolization were reported in 9 (33.3%) of the patients, involving the upper and lower extremities (55.6%), brain ischemia and vision loss (54.4%). Tumors in all patients were successfully resected under cardiopulmonary bypass support. The tumor was pedunculated in 17 (62.9%) of the patients and the size of the tumors varied from 1 to 7 centimeters in diameter. The tumor was located in the left atrium in 21 patients (77.7%), in the right atrium in 4 patients (14.8%), in the right ventricular side of the septum in 1 patient (3.7%) and involving the tricuspid valve in 1 patient (3.7%). The left atrial approach was used in 3 patients, a right atrial approach in 4 patients and a bi-atrial approach in 20 patients. The most common concomitant cardiac pathology was coronary artery disease in 3 patients and an atrial septal defect in one patient. The most common intra-operative challenges were inter-atrial communication (2 patients), large defect in the tricuspid valve leaflet (1 patient) and involvement of the inter-ventricular septum (1 patient). In the post-operative period, 1 patient suffered a stroke. In the post-operative period, the most common complications were stroke (1 patient) and recurrence of the tumor (2 patients). CONCLUSION: The success rate after surgical removal of cardiac myxoma in this study was substantial and complications were rare.

Aortopulmonary ectopic parathyroid gland and concurrent thymolipoma.

Ectopic parathyroid adenomas are considered the main cause of primary hyperparathyroidism. However, concurrent parathyroid and thymic pathologies are rarely diagnosed in the same patient. A 47-year-old man with history of diabetes mellitus, hypertension, and myasthenia gravis presented with persistent hypercalcemia. Laboratory investigations, computed tomography, and technetium-99 m sestamibi scintigraphy revealed ectopic parathyroid glands, a mediastinal mass, and an enlarged thymus. The patient underwent thymectomy and mass excision via a median sternotomy. Histopathology was consistent with ectopic parathyroid adenoma and thymolipoma. The serum calcium and parathormone concentrations normalized within 48 hours after surgery.

Interaction of testosterone with inhibin alpha and betaA subunits to regulate prostate gland growth.

Testosterone regulation of prostate gland growth has been shown to involve reciprocal interaction with inhibin and activin. This study was therefore conducted to correlate the effect of testosterone on prostate gland proliferation and differentiation with the level of expression of inhibin alpha and betaA subunits. Immature dogs were treated with testosterone for 0, 3, 7, and 14 days and prostate gland growth was assessed by morphological and immunohistological localization of differentiation and proliferation markers. The results showed that testosterone treatment resulted in an initial significant increase in PCNA proliferation index by days 3 and 7, followed by a significant decrease by day 14 post-treatment. Interestingly, the decrease of cell proliferation was associated with structural and biochemical changes characteristic of glandular and stromal differentiation of the prostate gland. These changes include progressive glandular ductal canalization and inter-ductal stroma differentiation which were apparent from a gradual shift from vimentin expression to vimentin and alpha-actin expression. Testosterone also had a differential effect on inhibin alpha and beta subunits. Although testosterone treatment resulted in significant and constant inhibition of alpha subunit mRNA expression, it resulted in a significant increase of betaA mRNA expression by day 3, followed by a decrease by days 7 and 14. These results indicated that testosterone acts first to drive proliferation of undifferentiated prostatic cells and then to maintain a low proliferation turnover of differentiated cells. Because it has been shown that activin is an antagonistic regulator of androgens, the attenuated stimulatory effect of testosterone on cell proliferation by day 14 might be mediated, at least in part, by interplay between testosterone and activin.

Effect of castration on extracellular matrix remodeling and angiogenesis of the prostate gland.

This study was conducted to evaluate the long term effect of castration on the prostate gland proliferation, extracellular matrix remodeling and angiogenesis. Prostate gland proliferation was assessed by immunolocalization of proliferating cell nuclear antigen (PCNA). The expression level of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-beta) and metaloprotenase-13 (MMP-13) by the prostate gland were assessed by immunohistochemistry and quantitative real-time PCR. The expression of the above mentioned parameters by the prostate gland of mature intact dogs were compared to that of castrated dogs six months post-castration. The results showed that castration induced a remarkable atrophy of the prostate gland which was associated with a highly significant decrease in the PCNA proliferation index. Although TGF-beta protein was immunolocalized to the epithelial and stroma cells of the prostate gland from both intact and castrated dogs, castration induced a significant up-regulation of TGF-beta mRNA expression. VEGF mRNA expression and its encoded protein immunolocalization were decreased significantly by the prostate gland from castrated dogs as compared to that of intact dogs. Castration, on the other hand, resulted in no significant change in MMP-13 mRNA expression despite an effect on its cellular immunolocalization which appeared to be localized to the epithelial and stromal cells of the prostate gland from castrated dogs as compared to epithelial cells of the prostate gland from intact dogs. These results indicated that castration-induced prostate gland regression continued to exert a potent suppressive effect on prostate gland proliferation which might be mediated by the elevated level of TGF-beta. Moreover, the low expression level of VEGF might reflect a reduced blood flow demand by the regressed and growth-dormant prostate after castration.

Unusual presentation of splenic myelolipoma in a dog.

A 13-year-old dog was presented with clinical signs of anemia, vomiting, weight loss, and progressive abdominal distension. Abdominal ultrasonography and radiography revealed a large mass, which was removed surgically. Cytologic and histologic evaluation of the mass revealed a mixture of fat and hematopoietic tissue, consistent with a splenic myelolipoma.