BACKGROUND: Leptin as a cytokine-like hormone is derived from ob gene (one of the major effect genes on birth weight and growth traits) and is secreted by adipose tissue. This hormone with binding to its receptors in the hypothalamus, inhibits food intake and increases energy consumption. OBJECTIVES: There is not any report about expression of leptin gene in response to oral administration of selenium in livestock. In the present study, the effects of selenium nanoparticle and sodium selenite on the transcription of leptin gene in placenta were studied. METHODS: Twenty, four-month pregnant ewes within the same age were selected randomly. During the 21 days leading up to birth, oral administration of selenium nanoparticles (Se NPs) with dosages of 0.05 and 0.10 mg/kg B.W. and sodium selenite with dosage of 0.1 mg/kg B.W. was carried out. At the same time the control group was fed distilled water in equal volume. With sampling of the placenta during childbirth, transcription amount of leptin gene was determined by RT PCR Real Time based on a comparison assay of 2-ΔΔCt. Results: The results of this study showed that leptin gene is expressed in placental tissue. The oral administration of selenium nanoparticle and sodium selenite caused a significant increment in terms of expression of mentioned gene in comparison to the control treatment. Also, there was a significant difference between the supplements, so that the highest leptin gene expression in placenta was observed in selenium nanoparticle treatment with dose of 0.1 mg and then supplement with selenium nanoparticles with dose of 0.05 mg. CONCLUSIONS: Selenium causes an increment of leptin gene expression in placental tissue.

Introduction: Staphylococcus pseudintermedius and Malassezia pachydermatis often cause skin diseases in dogs. Material and Methods: An online survey was e-mailed to veterinary practices nationwide covering demographics, diagnosis methods, and oral and topical treatment options. Of the 740 surveys sent, 100 complete replies were obtained. Results: The majority of clinicians were unaware of the existence of the International Society for Companion Animal Infectious Diseases guidelines or did not follow them (53%). Oral antibiotics were used universally for superficial bacterial folliculitis treatment, particularly amoxicillin-clavulanic acid (100%), cephalexin (94%), enrofloxacin (67%), or marbofloxacin (60%). For fold dermatitis (FD) and otitis externa (OE), oral antibiotics were also given as treatment in 88% and 82% of cases, respectively. Oral antifungals were often prescribed for generalised Malassezia dermatitis (85%), FD (70%), and OE (59%). S. pseudintermedius and M. pachydermatis were frequently treated topically, particularly with antibacterials or antifungals only, or a combination of antibacterials, antifungals, and glucocorticoids. Alternative options such as honey-based products were not frequently used. Conclusion: Our survey suggests that oral antibiotics are overused by Portuguese clinicians despite the spread of antibiotic resistant S. pseudintermedius. Oral antibiotics and antifungals are commonly prescribed for skin conditions manageable with topical treatments.

Introduction: The study aimed to investigate the anti-fertility effect of fennel (Foeniculim vulgare Mill) seed extract in male rats.Material and Methods: Forty Wistar rats were divided into five equal groups. The control group received distilled water and the experimental groups were orally administered 1 ml of hydro-alcoholic extract of fennel seed in four doses of 35, 70, 140, and 280 mg/kg/b.w. daily for 60 days. After the last gavage, the rats were anaesthetised and the caudal part of the right epididymis was used for sperm counting. After fixation of the testes, microscopic sections were prepared and histological changes were evaluated.Results: The number of spermatogonia after doses of 140 and 280 mg/kg and Sertoli cells after a dose of 140 mg/kg decreased significantly as compared with the control group (P < 0.05). The number of primary spermatocytes and sperm count decreased significantly in the experimental groups (70, 140, and 280 mg/kg) when compared to the control group (P < 0.05). Furthermore, thickening of the basement membrane, cell apoptosis, and irregular arrangement of the germinal epithelium were observed in the experimental groups.Conclusion: Hydro-alcoholic fennel seed extract at these doses could reduce reproductivity and has anti-fertility activity in male rats.

Simvastatin is a substance which is commonly used as a medicine to reduce cholesterol level. Unfortunately, it shows numerous side effects. Simvastatin affects various internal organs, and among other detriments to health may cause persistent muscle weakness, osteolytic processes, headaches, and rashes. Until now knowledge of the influence of simvastatin on bone marrow cells has been rather scant and fragmentary. During this experiment the numbers of all types of cells in the leukocytic system of porcine bone marrow were evaluated after 28 and 56 days of oral administration of simvastatin at a dose of 40 mg/day/animal. Simvastatin caused an increase in the number of all types of cells in the leukocytic system, and the most visible fluctuations concerned promyelocytes. Observations obtained during the present study indicated that the results of the action of simvastatin on porcine bone marrow differ from those observed in other mammal species, including human. This may be due to various metabolic pathways within the bone marrow in the particular species, but the exact mechanisms of these actions are unknown at the present time.

Nerium oleander is a plant of the Apocynaceae family toxic to humans, animals, and insects. This study was performed to determine the cardiac and neurotoxicity of the plant extract by oral administration in Wistar rats and Balb/c mice and to compare the susceptibility of these animal models to oleander toxicity. Four groups of eight mice and eight rats received N. oleander extract orally while a fifth group was the control. Serum concentrations of the biochemical toxicity indicators, namely troponin and creatine kinase (CK), were determined and histopathological evaluation of the heart and brain was performed. In mice, CK and troponin concentrations were respectively 1.5 and 7 times higher than in the control group (P < 0.05), while in rats, they were 6–7 and 11 times higher. Hyperaemia, haemorrhage, and myofibrolysis, without infiltration of inflammatory cells, were observed in the heart. In the brain the authors observed hyperaemia associated with perivascular and perineuronal oedema, and in higher-dosed rats multifocal haemorrhagic and liquefactive necrotic lesions. Oleander can affect serum levels of CK and troponin due to nervous and cardiac injuries. Rats showed more severe changes in the biochemical indicators and histopathological lesions than mice. Therefore, biochemical and pathological findings indicate that Wistar rats are more susceptible to the cardiac toxicity and neurotoxicity effects of N. oleander poisoning than Balb/c mice.

Introduction: Thyroid hormones affect protein turnover, and in the case of hypothyroidism a decrease in protein synthesis and reduced release of certain amino acids from skeletal muscles are observed. Changes in the amino acid system of skeletal muscles may be responsible for the occurrence of muscle disorders. Material and Methods: The study measured the content of selected amino acids in the gastrocnemius muscle of Wistar rats during experimental hypothyroidism induced by oral administration of methimazole at a concentration of 0.05% in drinking water for 90 d. The rats were divided into four groups: E1 (n = 6) - experimental males, E2 (n = 6) - experimental females, C1 (n = 6) - control males, and C2 (n = 6) control females. Results: A statistically significant reduction occurred in leucine, isoleucine, and 1-methylhistidine levels in males, and 1-methylhistidine in females, in comparison to the control groups. Conclusion: The hypothyroidism-induced changes in amino acid content may be responsible for the occurrence of skeletal muscle function disorders.

Veterinarians use flumequine (FLU) widely but its toxicological effects are still unclear. FLU doses of 53, 200, or 750 mg/kg were administered orally for six weeks to pubertal male rats for evaluation of their toxicity. Weight gain was poorer after seven days of exposure to FLU 750, but relative weights of the brain, adrenal and thyroid glands, and testes were notably higher. Haematological and lipid profile parameters, cardiac markers, and inorganic phosphate significantly increased in the FLU 750 group. Blood glucose, oestradiol and serum concentrations of immunoglobulins G (IgG) and E (IgE) significantly decreased after treatment. The levels of interleukins 10 (IL-10) and 6 (IL-6) fell significantly in the FLU 200 and FLU 750 groups. Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and cyclooxygenase-2 (Cox-2) expression amplified after treatment. Serum levels of free triiodothyronine (fT3) and free thyroxine (fT4) reduced in the FLU 200 and FLU 750 groups without changes in total T3 or T4 level. All doses of FLU significantly depressed concentrations of thyroid-stimulating hormone (TSH) and testosterone. Histopathology of thyroid glands from rats treated with FLU 750 showed degeneration and depletion of thyroid follicular epithelial cells. Expression of 8-hydroxydeoxyguanosine (8-OHdG) was increased in a dose-dependent manner in the brain, but decreased in the testes. Expression of CYP1A1 increased in the adrenal and pituitary glands. The results of this study suggest that the toxicity of FLU in rats is an effect of its disruptive influence on the pituitary-thyroid hormonal system and on the dysfunction of the immune system.

OBJECTIVE To investigate the effects of orally administered trazodone on intraocular pressure (IOP), pupil diameter measured in the vertical plane (ie, vertical pupil diameter [VPD]), selected physical examination variables, and sedation level in healthy equids. ANIMALS 7 horses and 1 pony. PROCEDURES Food was withheld for 12 hours prior to drug administration. After baseline (time 0) sedation scoring, physical examination, and measurement of IOP and VPD, equids received 1 dose (approx 6 mg/kg) of trazodone orally. Examination and measurement procedures were repeated 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Blood samples were collected at each time point for analysis of plasma trazodone concentrations. Repeated-measures analysis was used to compare examination results between downstream time points and baseline. RESULTS 7 of 8 equids had mild sedation from 0.5 to 8 hours after treatment; compared with baseline values, mean IOP was significantly lower from 0.5 hours to 8 hours, mean VPD was significantly smaller at 0.5 hours, and mean rectal temperature was significantly lower from 1 to 8 hours after drug administration. Adverse effects (signs of excitement in 1 equid and sweating in 4) were self-limiting and considered minor. Mean maximum plasma concentration of trazodone was 1,493 ng/mL 0.75 hours after administration, and terminal half-life of the drug was 9.96 hours. CONCLUSIONS AND CLINICAL RELEVANCE The described oral dose of trazadone elicited sedation with a few self-limiting adverse effects in the study sample. Drug effects on IOP and VPD may alter ocular examination findings. Further investigation is warranted prior to use of trazodone for sedation in equids, particularly those with ophthalmic conditions.

OBJECTIVE To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses. ANIMALS 12 healthy adult horses. PROCEDURES In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg, PO, q 48 h for an additional 30 days). RESULTS Following IV (single-dose) or PO (single- or multiple-dose) administration, MMF was rapidly converted to mycophenolic acid. For single-dose PO administration, mean ± SD maximum plasma mycophenolic acid concentration was 1,778.3 ± 441.5 ng/mL at 0.71 ± 0.29 hours. For single-dose IV administration, mean systemic clearance and volume of distribution at steady state were 0.689 ± 0.194 L/h/kg and 1.57 ± 0.626 L/kg, respectively. Following single doses, mean terminal half-life was 3.99 ± 0.865 hours for IV administration and 4.02 ± 1.01 hours for PO administration. The accumulation index following long-term PO administration was 1.0 ± 0.002, and the terminal half-life was 4.59 ± 1.25 hours following the final dose on day 60. None of the horses developed abnormal clinical signs or had any consistently abnormal clinicopathologic findings. CONCLUSIONS AND CLINICAL RELEVANCE Further investigation of the clinical efficacy of long-term MMF treatment of horses with autoimmune diseases is warranted.

OBJECTIVE To determine the safety and pharmacokinetics of various doses of plant-derived cannabidiol (CBD) versus placebo following repeated oral administration. ANIMALS 20 healthy adult Beagles. PROCEDURES In a randomized, blinded, placebo-controlled trial, dogs were randomized to 5 groups balanced in body weight and sex (n = 4 dogs/group) and received a CBD (1, 2, 4, or 12 mg/kg; from cannabis extract) or placebo oil formulation PO once daily for 28 days. Outcome variables were assessed through daily health observations, veterinary examinations, CBC, and serum biochemical analysis. Blood samples were collected at various time points to estimate 24-hour pharmacokinetic profiles of CBD and selected metabolites (7-carboxy-CBD and 7-hydroxy-CBD). RESULTS Repeated CBD administration was well tolerated by dogs, with no clinically important changes in measured safety outcomes. Veterinary examinations revealed no clinically important abnormal findings. Adverse events were mild in severity. Relative to placebo administration, CBD administration at 12 mg/kg/d resulted in more gastrointestinal adverse events (mainly hypersalivation) and significantly higher serum alkaline phosphatase activity. Total systemic exposure to CBD increased on a dose-dependent basis following both acute (first dose) and chronic (28 days) administration. Within each CBD dose group, repeated administration increased total systemic exposure to CBD 1.6- to 3.3-fold. The 24-hour trough plasma CBD concentrations were also dose dependent, with a steady state reached following 2 weeks of administration. CONCLUSIONS AND CLINICAL RELEVANCE Repeated, daily oral administration of the CBD formulation led to dose-dependent increases in total systemic exposure to CBD and 24-hour trough plasma concentrations in healthy dogs. These findings could help guide dose selection.