Concentrations of medetomidine enantiomers and vatinoxan,an α2-adrenoceptor antagonist,in plasma and central nervous tissue after intravenous coadministration in dogs

ObjectiveTo quantify the peripheral selectivity of vatinoxan (L-659,066, MK-467) in dogs by comparing the concentrations of vatinoxan, dexmedetomidine and levomedetomidine in plasma and central nervous system (CNS) tissue after intravenous (IV) coadministration of vatinoxan and medetomidine.Study designExperimental, observational study.AnimalsA group of six healthy, purpose-bred Beagle dogs (four females and two males) aged 6.5 ± 0.1 years (mean ± standard deviation).MethodsAll dogs were administered a combination of medetomidine (40 μg kg⁻¹) and vatinoxan (800 μg kg⁻¹) as IV bolus. After 20 minutes, the dogs were euthanized with an IV overdose of pentobarbital (140 mg kg⁻¹) and both venous plasma and CNS tissues (brain, cervical and lumbar spinal cord) were harvested. Concentrations of dexmedetomidine, levomedetomidine and vatinoxan in all samples were quantified by liquid chromatography–tandem mass spectrometry and data were analyzed with nonparametric tests with post hoc corrections where appropriate.ResultsAll dogs became deeply sedated after the treatment. The CNS-to-plasma ratio of vatinoxan concentration was approximately 1:50, whereas the concentrations of dexmedetomidine and levomedetomidine in the CNS were three- to seven-fold of those in plasma.Conclusions and clinical relevanceWith the doses studied, these results confirm the peripheral selectivity of vatinoxan in dogs, when coadministered IV with medetomidine. Thus, it is likely that vatinoxan preferentially antagonizes α₂-adrenoceptors outside the CNS.     

Plasma glucose, insulin, free fatty acids, lactate and cortisol concentrations in dexmedetomidine-sedated dogs with or without MK-467: A peripheral α-2 adrenoceptor antagonist

Six healthy laboratory Beagles were treated IV with 10μg/kg dexmedetomidine (DEX) or 10μg/kg dexmedetomidine combined with 500μg/kg MK-467 in the same syringe (DMK) in a randomised cross-over design with a 14day washout. Blood was collected immediately before treatment and 35, 60 and 120min post-injection through a central venous catheter. The plasma concentrations of glucose, insulin, non-esterified free fatty acids (NEFAs), lactate and cortisol were determined. A repeated-measures ANOVA test was used to compare treatments and effects for each sample time point. Significant differences between treatments were found for plasma glucose (P=0.037) and insulin (P=0.009). DEX significantly increased plasma glucose at 120min, but reduced plasma insulin at 35 and 60min. NEFA decreased for both treatments at 35min. This reduction was transient for DMK, whereas it persisted during the follow up period for DEX. Plasma lactate concentrations increased at 35 and 60min with DEX. Neither treatment altered plasma cortisol concentrations. The addition of MK-467 to dexmedetomidine prevented or abolished most metabolic changes in healthy Beagles.     

Adverse reactions of α2-adrenoceptor agonists in cats reported in 2003–2013 in Finland

Objective

To describe suspected adverse drug reactions in cats associated with use of α₂-adrenoceptor agonists.

The effects of repeated intravenous iohexol administration on renal function in healthy beagles – a preliminary report

Background

Contrast induced nephrotoxicity (CIN) is a well described syndrome in humans undergoing contrast medium examinations. To date CIN has received minimal attention in the veterinary literature despite increasing use of contrast medium examinations in computed tomographic studies.

Methods

This prospective study evaluated the effect of 1290 mg/kg iohexol given intravenously to 5 normal beagle dogs in a divided dose at an interval of 6–8 weeks. Renal function was evaluated by means of scintigraphically determined glomerular filtration rate (GFR) and a variety of laboratory assays.

Results

Only GFR showed a significant decrease (17%) after the second injection but not to a clinically or pathologically significant level.

Conclusions

No clinically significant effect of repeated contrast medium administration was determined in this limited study. However in dogs with reduced renal function the risk of CIN is likely to increase dramatically post contrast administration.     

The effect of two different routes of administration of oxytocin on peripheral plasma prostaglandin F(2α) metabolite levels in early post-partum dairy cows

Various parenteral treatment forms of oxytocin, as often used under praxis circumstances, may act differently on contractility of the uterus during the first days of the puerperium. Various patterns of such induced uterotonic responses may lead to alterations in the emptying characteristics of the uterine lumen, thus influencing, as a late consequence, the process of involution. Therefore, this study was designed to test whether two different parenteral administration forms of oxytocin induce changes in peripheral plasma concentrations of 15-ketodihydro-prostaglandin F(2α) (PGF(2α) metabolite) in early post-partum cows. Between 13 and 15 h after uncomplicated calving, healthy dairy cows without retained foetal membranes were treated with 50 IU oxytocin, either intramuscularly (OT-IM group; n = 15) or intravenously (OT-IV group; n = 16). Saline solution was administered intramuscularly as controls (CON group; n = 15). Jugular blood samples were taken at 10-min intervals from 1 h before to 2 h after treatment. Plasma PGF(2α) metabolite levels were measured by radioimmunoassay. No significant differences in peripheral plasma PGF(2α) metabolite concentrations occurred in the OT-IM and CON groups, but mean values significantly increased in the OT-IV group, peaking at 20 min after treatment and reaching pre-treatment baseline values again at 120 min. Although the source of prostaglandins was not investigated in this study, our results suggest that exogenous oxytocin may enhance secretion of prostaglandins by the uterus during the first day after normal calving. These prostaglandins might contribute, by an endocrine or paracrine route, to the stimulation of myometrial contractility when exogenous oxytocin is given during this early post-partum stage.     

The effect of geographic location, breed, and pituitary dysfunction on seasonal adrenocorticotropin and α-melanocyte-stimulating hormone plasma concentrations in horses

Background: Plasma α‐melanocyte‐stimulating hormone (α‐MSH) and adrenocorticotropin (ACTH) concentrations in horses vary with season, confounding diagnostic testing for pituitary pars intermedia dysfunction (PPID). Hypothesis: The goals of this study were to determine whether seasonal variation in plasma α‐MSH and ACTH concentrations in horses is influenced by geographic location, breed, or PPID. Animals: Healthy light breed horses residing in Florida, Massachusetts, and Finland (n = 12 per group); healthy Morgan horses (n = 13); healthy ponies (n = 9) and horses with PPID (n = 8). Methods: Monthly plasma α‐MSH and ACTH concentrations were measured by radioimmunoassay. Nonlinear regression analysis was used to estimate the time of peak hormone concentrations. Mean hormone concentrations in fall and nonfall months were compared. Results: The fall peak plasma α‐MSH concentration occurred earlier in horses residing at more northern locations. Mean seasonal α‐MSH concentrations were similar in all healthy groups at all locations, but in the fall, plasma ACTH concentrations were higher in horses living in more southern locations. Plasma ACTH but not α‐MSH concentrations were higher in Morgan horses compared with light breed horses from the same location. Hormone concentrations of ponies did not differ from those of horses during either season. Concentrations of both hormones were high in the fall compared with the spring in horses with PPID. Conclusions and Clinical Importance: These findings suggest geographic location of residence and breed may affect the onset, amplitude, or both of the seasonal peak of pars intermedia (PI) hormones and should be considered when performing diagnostic testing for PPID. Horses with PPID maintain seasonal regulation of PI hormone output.     

Effects of intramuscular and intranasal administration of midazolam–dexmedetomidine on sedation and some cardiopulmonary variables in New Zealand White rabbits

ObjectiveTo compare the sedative and cardiopulmonary effects of intranasal (IN) and intramuscular (IM) administration of dexmedetomidine and midazolam combination in New Zealand White rabbits.Study designA randomized, crossover experimental study.AnimalsA total of eight healthy New Zealand White rabbits, aged 6–12 months, weighing 3.1 ± 0.3 kg (mean ± standard deviation).MethodsThe animals were randomly assigned to administration of dexmedetomidine (0.1 mg kg^–1) with midazolam (2 mg kg^–1) by either IN or IM route separated by 2 weeks. The electrocardiogram, pulse rate (PR), peripheral haemoglobin oxygen saturation (SpO₂), mean noninvasive arterial pressure (MAP), respiratory frequency (f_R) and rectal temperature were measured before drug administration (baseline), T₀ (onset of sedation) and at 5 minute intervals until recovery. The onset of sedation, duration of sedation and sedation score (SS) were also recorded.ResultsThe PR was significantly lower in treatment IM than in treatment IN over time (p = 0.027). MAP < 60 mmHg developed in two and four rabbits in treatments IN and IM, respectively. SpO₂ progressively decreased over time in both treatments. f_R was lower than baseline at several time points in both treatments. Onset of sedation was shorter in treatment IN (90 ± 21 seconds) than in treatment IM (300 ± 68 seconds) (p = 0.036). Duration of sedation was longer in treatment IM (55.2 ± 8.7 minutes) than in treatment IN (39.6 ± 2.1 minutes) (p = 0.047). No significant difference in SS was observed between treatments (p > 0.05).Conclusions and clinical relevanceCombination of dexmedetomidine (0.1 mg kg^–1) and midazolam (2 mg kg^–1) decreased f_R, PR and SpO₂ regardless of the administration route in New Zealand White rabbits. A more rapid action and shorter duration of sedation were observed after treatment IN than after treatment IM administration.     

The effect of α-tocopherol,sweet chestnut wood extract and their combination on oxidative stress in vivo and the oxidative stability of meat in broilers

1. This study examined the effect of α-tocopherol (α-T), sweet chestnut wood extract (SCW) and their combination on oxidative stress in vivo and oxidative stability of meat in broilers given diets rich in PUFA.

2. A total of 60 male broilers were individually caged and divided into 6 groups of 10. The C-PALM group received a diet with 7·5% palm fat and the other 5 groups with 7·5% linseed oil. The linseed oil groups were either un-supplemented (C-LIN) or supplemented with α-T or/and SCW as follows: αT-85 (C-LIN diet?+?68?IU vit E as all-rac-α-T/kg), αT-200 (C-LIN diet?+?183?IU vit E as all-rac-α-T/kg), SCW (C-LIN diet?+?3?g SCW/kg) and αT-SCW (C-LIN diet?+?68?IU vit E as all-rac-α-T/kg?+?3?g SCW/kg). Different parameters of oxidative stress were measured.

3. Linseed oil induced DNA fragmentation and malondialdehyde (MDA) formation, while α-T reduced both parameters, and SCW reduced the DNA damage. A combination (αT-SCW) also reduced plasma MDA. Larger antioxidant capacity of lipid soluble compounds were recorded in groups αT-85, αT-200 and αT-SCW than in the controls but there were no differences between these groups in antioxidant enzymes and total antioxidant status. A combination (αT-SCW) increased tocopherol concentrations in breast muscle and in comparison to the C-LIN group MDA concentrations were reduced in groups αT-85, αT-200 and αT-SCW.

4. It can be concluded that neither of the α-T concentrations were able to prevent all the negative effects of lipid oxidation in vivo and only high concentrations of α-T improved the stability of meat. With the exception of DNA damage, SCW had no impact on in vivo and in vitro measured markers of oxidative stress but may have a sparing or regenerating effect on α-T.     

The effect of severe drought and management after drought on the mortality and recovery of semi‐arid grassveld

Abstract

The False Thornveld of the Eastern Cape experienced a particularly intense drought during the 1982/83 growing season. Extensive grass mortality took place during the drought. After the drought, recovery was particularly sensitive to the post‐drought management treatment applied. Veld that was grazed immediately after the drought recovered far more slowly than veld that was rested. This effect was still evident three years later, illustrating the considerable importance of resting semi‐arid grassveld after a drought.

Increaser I grass species present were apparently more capable of surviving drought than the Decreaser species, which in turn were more stable than the Increaser II species. Their ability to recover after the drought followed an opposite trend. On this basis, the desirability of Decreaser dominated veld, in situations that are likely to be poorly managed, is questioned.     

Pathological,biochemical and haematological investigations on the protective effect of α-lipoic acid in experimental aflatoxin toxicosis in chicks

1.?The purpose of this study was to investigate the protective effect of α-lipoic acid (LA) on aflatoxin (AF) toxicosis in chicks.

2.?Groups of 10 Ross PM3 chicks were given, for 21 d, no AF (C), 60 mg/kg/bwt of α-lipoic acid (LA), 150 ppb of aflatoxin (AF1), 150 ppb of aflatoxin plus 60 mg/kg/bwt of α-lipoic acid (AF1 + LA), 300 ppb of aflatoxin (AF2), and 300 ppb of aflatoxin plus 60 mg/kg/bwt of α-lipoic acid (AF2 + LA). Before the animals were killed, blood samples were drawn for haematological analysis, and then tissue samples were collected for histopathological investigation. Immunohistochemical staining was performed against inducible nitric oxide synthase (iNOS) and nitrotyrosine on liver samples. Apoptotic cell death in liver was assessed by in situ TUNEL assay. The malondialdehyde (MDA) and reduced glutathione (GSH) concentrayions in liver and kidney were also determined.

3.?Hydropic degeneration and occasional necrosis, bile duct hyperplasia and periportal fibrosis were observed in the livers of AF-treated groups. The severity of these changes was reduced in LA-supplemented AF groups. Occasionally, thymic cortical atrophy, lymphoid depletion in spleen and bursa of Fabricius, and degeneration in the kidney tubule epitheliums were detected in AF groups. The severity of these degenerative changes was slightly reduced in LA supplemented groups.

4.?There was moderate to strong iNOS and nitrotyrosine immunoreactivity in the livers of AF groups, while decreased immunoreactivity was observed against both antibodies in the LA supplemented groups. Apoptotic cells were numerous in the AF groups, while greatly reduced in LA supplemented groups.

5.?In the liver and kidney of AF-treated groups given 300 ppb of aflatoxin, MDA concentrations were increased as GSH decreased, compared to the control group. LA supplementation of AF-treated birds improved the results compared to the AF only groups, however a statistical difference was observed only in liver tissues between AF2 + LA and AF2 groups. Haematological variables showed no differences among the groups.

6.?In conclusion, supplementation of feed with the antioxidant LA, might ameliorate the degenerative effects caused by aflatoxin due to lipid peroxidation.     

Comparative immune response and pathogenicity of the H9N2 avian influenza virus after administration of Immulant®, based on Echinacea and Nigella sativa,in stressed chickens

Avian influenza vaccines are commonly used in the poultry industry, and some medicinal plants can increase the efficacy of such vaccines. The objective of this study was to evaluate the effect of Immulant^® (IMU) (a commercial product based on Echinacea and Nigella sativa) on stress induced by dexamethasone (DEX) in chickens vaccinated (VAC) against the H9N2 avian influenza virus (AIV-H9N2). Seven experimental groups were included: the negative control, VAC, DEX, VAC + DEX, VAC + DEX + IMU, VAC + IMU and IMU groups. The vaccinated chickens (at 10 days of age) were injected daily with DEX for three days pre-vaccination and for three days pre-challenge and orally administered 1% IMU for 6 weeks post-vaccination (PV). The chickens were then challenged intranasally with AIV-H9N2 at 28 days PV. Serum, blood, tracheal and cloacal swabs and tissue samples were collected in the 1^st and 4^th weeks PV and at different time points post-challenge. The results showed significant changes (P ≤ 0.05) in oxidative stress and antioxidant biomarkers (malondialdehyde, nitric oxide and reduced glutathione), haematological and immunological parameters, final live weights, relative organ weights and histopathological lesions between the VAC+DEX group and the VAC group. Moreover, IMU significantly increased protection rates post-challenge, HI antibody titers and heterophil phagocytic activity and decreased DEX-induced stress and virus shedding titers. In conclusion, oral administration of 1% IMU for six weeks can enhance the immune response after AI-H9N2 vaccination and reduce the pathogenicity of infection in stressed chickens.     

Effect of non-steroidal anti-inflammatory drugs on glomerular filtration rate and urinary N-acetyl-β-D-glucosaminidase activity in cats after dental surgery

ObjectiveTo compare the effects of meloxicam or carprofen on glomerular filtration rate (GFR), and to evaluate the effect of meloxicam on urinary N-acetyl-β-D-glucosaminidase (NAG) activity, of cats after dental surgery.Study designRandomized, blinded, controlled trial.AnimalsA total of 24 mixed breed cats.MethodsCats were randomly assigned to one of three groups (n = 8 per group): meloxicam (0.2 mg kg^–1); carprofen (4 mg kg^–1); or saline (2 mL). Acepromazine (0.04 mg kg^–1) and buprenorphine (0.02 mg kg^–1) were administered intramuscularly as preanaesthetic medication. Test drugs were injected subcutaneously at the time of preanaesthetic medication. Anaesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. Mean arterial blood pressure (MAP), respiratory rate (f_R), heart rate (HR) and haemoglobin oxygen saturation values (SpO₂) were recorded. All cats underwent ultrasonic dental scaling with polishing. Teeth extraction involved mucosal flap creation, removal of alveolar bone and flap closure. Plasma iohexol clearance (ICL), a measure of GFR, was estimated before and 24 hours after anaesthesia induction in all cats. Urinary NAG index was estimated in saline and meloxicam groups at the same time points as GFR. Between-group and -time point differences in GFR and NAG index were compared using mixed model analyses. Data are presented as mean ± standard deviation (p < 0.05).ResultsThere was no significant difference in plasma ICL rate (range: from 1.22 ± 0.05 to 1.27 ± 0.04 mL kg minute^–1) between groups or between time points. Urinary NAG index (range: from 1.0 ± 0.19 to 1.36 ± 0.29 Units gram^–1) was not significantly different between meloxicam and saline groups. MAP, HR, f_R and SpO₂ did not differ significantly between groups.Conclusions and clinical relevanceMeloxicam and carprofen appeared to produce nonsignificant effects on GFR, and meloxicam did not affect the urinary NAG activity, of cats after dental surgery.     

The effect of a pressure wrap (ThunderShirt®) on heart rate and behavior in canines diagnosed with anxiety disorder

The effect of moderate-to-deep pressure on soft tissue has been studied in both humans and nonhuman animals with positive results shown in reducing anxiety and promoting relaxation. Canine anxiety disorders are often treated with medications and behavior modification programming. Pressure wraps are sometimes used to treat canine anxiety, but the effects of this investigation have not been rigorously investigated. The aims of this study were to investigate the use of a pressure wrap (ThunderShirt®; ThunderWorks, Durham, NC) on heart rate and behavior in dogs diagnosed with an anxiety disorder. Subjects were 90 dogs (39 males and 51 females) that were diagnosed with Separation Anxiety or Generalized Anxiety Disorder. Dogs were randomly assigned to 1 of the 3 groups, namely Experimental Group 1 (dogs wore the ThunderShirt® per manufacturer's recommendations), Experimental Group 2 (dogs wore the ThunderShirt® loosely without pressure), and Control Group (dogs had no specific treatment). Average and maximum heart rates were measured at baseline and after 15 minutes alone in the kennel. Dogs were video-recorded and analysis completed for 12 behaviors, namely pacing, panting, yawning, tongue-flicking, drooling, elimination, barking, stress whining, howling, licking, door orientation, and calmness. The results were as follows: Dogs in Experimental Group 1 showed significantly less increase from baseline in average heart rate than the Control Group dogs (P < 0.001) and dogs in Experimental Group 2 (P < 0.001). Dogs in Experimental Group 1did not differ significantly from Control Group dogs in maximum heart rate when all dogs were considered, but did differ significantly from the Control Group (P = 0.04) when only those dogs not currently on anxiety medication were considered. There were no statistically significant differences among groups on behavioral outcomes, except that the dogs in the Control Group were significantly more likely to orient toward the door than the dogs in both Experimental Groups 1 (OR = 7.46, P = 0.01) and 2 (OR = 4.42, P = 0.04). Dogs in the Experimental Group 1 presented a trend of less tongue-flicking (P = 0.06) and yawning (P = 0.07) stress reduction behaviors when compared with the other 2 groups. More research should be conducted with the ThunderShirt® on behavioral outcomes. The ThunderShirt® can be used with behavior modification programming and medication as an adjunct treatment option to assist dogs diagnosed with anxiety disorder to reduce heart rate.     

The effect of probiotic BioPlus 2B® on growth performance,dry matter and nitrogen digestibility and slurry noxious gas emission in growing pigs

For this study, 2 experiments were conducted to evaluate the effects of dietary BioPlus 2B^® supplements on growing pigs. In experiment 1, 64 crossbred pigs (26.70 ± 0.50 kg) were subjected to a 35-day feeding trial (2 pigs/pen, 8 pens/treatment) in which the effects of the following four corn-soybean meal based dietary treatments were compared: 1) CON (basal diet); 2) B0.05 (basal diet + 0.05% BioPlus 2B^®); 3) B0.1 (basal diet + 0.1% BioPlus 2B^®) and 4) B0.2 (basal diet + 0.2% BioPlus 2B^®). During the experimental period, average daily gain (ADG) tended to increase in a linear fashion (P = 0.08) with increasing levels of dietary BioPlus 2B^®. In addition, the average daily feed intake (ADFI) was found to increase (P < 0.05) as the levels of BioPlus 2B^® increased. However, no linear or quadratic effects were observed in the gain:feed ratio (G:F) or in the coefficients of total tract apparent digestibility (CTTAD) when dry matter (DM) and nitrogen (N) were considered. In experiment 2, 16 crossbred barrows (25.60 ± 0.10 kg) were randomly allotted to 1 of the 4 dietary treatments used in experiment 1 (1 pig/pen, 4 pens/treatment). The noxious gas emissions and pH of slurry waste were then measured daily for 120 h. Ammonia (NH₃) emission from the slurry samples obtained from pigs in the BioPlus 2B^® groups was lower than that of slurry obtained from pigs in the CON treatment (P < 0.05), however, hydrogen sulfide (H₂S) and mercaptan emission were not affected by supplementation with BioPlus 2B^®. In addition, the pH value decreased with time, and the pH values of slurry obtained from pigs subjected to the B0.1 and B0.2 treatments were lower than those of samples obtained from other groups after 48 h (P < 0.05). Taken together, these results indicate that supplementation with BioPlus 2B^® can reduce slurry NH₃ emission, but not H₂S and mercaptan emission in growing pigs without impacting growth performance.     

The effect of reserpine on plasma LH concentrations in intact and Gona‐dectomised domestic fowl

1. Reserpine was found to inhibit the secretion of luteinising hormone when injected into intact and gonadectomised fowl at a dose rate which caused heavy sedation.

2. This could indicate that reserpine or its derivatives should not be used for breeding poultry.