The dose-response relationship in horses refers to the correlation between the dose of a substance, such as a drug or nutrient, and the magnitude of the response it elicits. This relationship is fundamental in pharmacology and toxicology, as it helps determine the appropriate dosage that achieves the desired therapeutic effect without causing adverse reactions. In equine studies, dose-response assessments are used to evaluate the efficacy and safety of medications, supplements, and other interventions. These studies involve varying the dose and observing the physiological or behavioral responses in horses, which may include changes in heart rate, blood parameters, or performance metrics. This page compiles peer-reviewed research studies and scholarly articles that explore the methodologies, findings, and implications of dose-response relationships in equine medicine and nutrition.
Castro-Cuellar G, Cremer J, Liu CC, Queiroz-Williams P, Hampton C, Leise BS.To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in vitro. Methods: Primary cultured equine articular chondrocytes from 3 healthy adult horses. Methods: Chondrocytes were exposed for 0 and 2 hours to the following treatments: media (CON; negative control); bupivacaine at 2.2 mg/mL (BUPI; positive control); morphine at 2.85 mg/mL (MOR); buprenorphine at 0.12 mg/mL (HBUPRE); or buprenorphine at 0.05 mg/mL (LBUPRE). Chondrocyte viability was assessed using live/dead staining, water-sol...
Alvarado TD, Elghandour MMMY, Ekanem NJ, Alcala-Canto Y, Velázquez AE, Pacheco EBF, Purba RAP, Salem AZM.The present study was conducted to investigate the aqueous extracts of Azadirachta indica (AZN), Cnidoscolus angustidens (CNA), and their combination (MIX) at dosages of 0-, 0.6-, 1.2-, and 1.8- mL for their ability to reduce greenhouse gases and fermentation profiles in an in vitro study using horse feces and a nutrient-dense diet (as substrate). The quantity of greenhouse gas and fermentation profiles were determined in in vitro incubation for 48 h. Extracts of AZN, CNA, and MIX reduced total gas production of the incubated and degraded substrates in a dose-dependent and time-dependent manne...
Pearson G, Goodale M, Wakshlag J, Fortier L.The objective of this study was to determine the effects of an oral, commercially available, marine based omega-3 fatty acid (n3-FA) supplement on fatty acid characteristics in horse whole blood. Fifty healthy, adult horses of various light breeds were assigned to one of two treatment groups: Group 1 receiving 7.5g/day of the test supplement, and Group 2 receiving 15g/day of the test supplement. The supplement contained 0.092g docosahexaenoic acid (DHA) and 0.148g eicosapentaenoic acid (EPA) per gram. Therefore, Group 1 received 1.11g of EPA and 0.69g of DHA daily, while Group 2 received 2.22g...
Pezzanite L, Chow L, Soontararak S, Phillips J, Goodrich L, Dow S.Equine veterinarians frequently inject aminoglycoside antibiotics intra-articularly, either to treat septic arthritis or for prophylaxis with other medications when injecting joints for osteoarthritis. Although aminoglycosides have been demonstrated to be toxic to equine mesenchymal stem cells (MSC), their effects on resident joint cells have not been previously investigated. Moreover, safe and effective intra-articular doses have not been defined. Objective: To determine effects of concentration, duration of exposure, pH and the presence of synovial fluid on the cytotoxic effects of amikacin ...
Sykes BW, Underwood C, McGowan CM, Mills PC.This study aimed to investigate the effect of diet and dose on the pharmacokinetics of omeprazole in the horse. Six horses received two doses (1 and 4 mg/kg) of omeprazole orally once daily for 5 days. Each dose was evaluated during feeding either a high-grain/low-fibre (HG/LF) diet or an ad libitum hay (HAY) diet in a four-way crossover design. Plasma samples were collected for pharmacokinetic analysis on days 1 and 5. Plasma omeprazole concentrations were determined by ultra-high pressure liquid chromatography-mass spectrometry. In horses being fed the HG/LF diet, on day 1, the area under...
Stefanski A, Mevissen M, Möller AM, Kuehni-Boghenbor K, Schmitz A.In this study, we established cell culture conditions for primary equine hepatocytes allowing cytochrome P450 enzyme (CYP) induction experiments. Hepatocytes were isolated after a modified method of Bakala et al. (2003) and cultivated on collagen I coated plates. Three different media were compared for their influence on morphology, viability and CYP activity of the hepatocytes. CYP activity was evaluated with the fluorescent substrate 7-benzyloxy-4-trifluoromethylcoumarin. Induction experiments were carried out with rifampicin, dexamethasone or phenobarbital. Concentration-response curves for...
Foreman JH, Bergstrom BE, Golden KS, Roark JJ, Coren DS, Foreman CR, Schumacher SA.There are no refereed controlled documentations of the skeletal analgesic efficacy of different dosages of flunixin meglumine (FM). Objective: The objective of this experiment was to compare the efficacy of various dosages of FM with a negative control. The hypothesis was that higher doses would result in improved efficacy in a dose-dependent manner when tested in a reversible model of foot lameness. Methods: Ten horses shod with adjustable heart bar shoes had weekly modified AAEP grade 4.0/5.0 lameness induced by tightening a set screw against the heart bar. Heart rate (HR) and lameness score...
Burton AJ, Giguère S, Warner L, Alhamhoom Y, Arnold RD.Therapeutic drug monitoring in a small number of foals of various ages indicates that the standard adult dose of 6.6 mg/kg bwt q. 24 h for gentamicin is too low and a dose of 12 mg/kg bwt has been proposed. The pharmacokinetics of this dosage in foals and the ages at which this higher dose should be used have not previously been investigated. Objective: To determine the effect of age on the pharmacokinetics of a single 12 mg/kg bwt i.v. dose of gentamicin in foals. Methods: Six healthy foals were given a single i.v. dose of gentamicin at 1-3 days, 2, 4, 8 and 12 weeks of age. Plasma concentrat...
Cuervo-Arango J, Newcombe JR.The objective of this study was to establish and characterize the relationship between the dose of cloprostenol (37.5, 250, 500 and 750 μg) and the age of the early corpus luteum (CL) (80, 88, 96, 104 and 112 h) on the luteolytic response of mares. Behavioural oestrus and ultrasonographic signs of return to oestrus were considered as the occurrence of full luteolysis. A total of 298 mares were divided into groups according to dose of cloprostenol and CL age. There was an effect of dose of cloprostenol (p < 0.001) and age of the CL at the time of treatment (p 0.05); and that of 500 similar...
Benbarek H, Ayad A, Deby-Dupont G, Boukraa L, Serteyn D.The purpose of this study was to explore the potential modulation of equine neutrophil oxidative burst by a series of classical NSAIDs which was subsequently monitored by the luminol or lucigenin-enhanced chemiluminescence (CL) technique. A significant dose-dependent inhibition of the luminol CL was observed with the majority of investigated drugs. This inhibition was very significant for phenylbutazone and Indomethacin; while for aspirin, a higher concentration is required. The action of Ketoprofen was significant during the first 5 min and only when the concentration was above 1 mM. Indometh...
Boly R, Dessy S, Kohnen S, Kini F, Lompo M, Mouithys-Mickalad A, Guissou IP, Dubois J, Deby-Dupont G, Serteyn D, Franck T.Agelanthus dodoneifolius DC Danser (Loranthaceae) is used for the treatment of various diseases including asthma. The aqueous and hydroalcoholic extracts have been reported to have anti-inflammatory, spasmolytic and bronchorelaxant activities. The present study investigates the effects of the aqueous decoction and the diethyl ether, ethyl acetate and butanolic fractions of Agelanthus dodoneifolius DC Danser (Loranthaceae) on reactive oxygen species (ROS) production and myeloperoxidase (MPO) release by phorbol 12-myristate 13-acetate (PMA)-stimulated equine neutrophils and on purified equine MP...
Cruz FS, Carregaro AB, Machado M, Antonow RR.This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min ...
Brosnan RJ, Steffey EP.We hypothesized that propofol can produce rapidly-reversible, dose-dependent standing sedation in horses. Methods: Prospective randomized, blinded, experimental trial. Methods: Twelve healthy horses aged 12 +/- 6 years (mean +/- SD), weighing 565 +/- 20 kg, and with an equal distribution of mares and geldings. Methods: Propofol was administered as an intravenous bolus at one of three randomized doses (0.20, 0.35 and 0.50 mg kg(-1)). Cardiovascular and behavioral measurements were made by a single investigator, who was blinded to treatment dose, at 3 minute intervals until subjective behavior s...
Sasaki N, Tsuzuki N, Yamada M, Minami T, Yamada H.This study aimed to establish a standard dose and sample collection time for (13)C phenylalanine and (13)C-Dipeptide breath test in horses. To evaluate dose-dependent effects, healthy horses received 2.5 mg/kg, 5 mg/kg, and 10 mg/kg (13)C phenylalanine dissolved in 1 ml/kg distilled water and 1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg (13)C dipeptide dissolved in 2 ml/ kg distilled water. Tmax was observed during the sample collection time. For (13)C phenylalanine, the standard deviation of Cmax at 5 mg/kg was lower than that of 10 mg/kg. For (13)C dipeptide, the standard deviation of Tmax was the low...
Camargo FC, Robinson NE, Berney C, Eberhart S, Baker S, Detolve P, Derksen FJ, Lehner AF, Hughes C, Tobin T.The bronchodilator effects of trimetoquinol (TMQ) have been studied when administered i.v. or intratracheally, but not in an aerosolised form. Objective: To define the relationship between the therapeutic and adverse responses (therapeutic index) of TMQ when administered as an aerosol or by the oral route. Methods: Increasing doses of TMQ were administered to horses with heaves as an aerosol and by the oral route. Dose ranged 100-1000 microg/horse for aerosolised TMQ and from 6-60 microg/kg bwt for the oral route. Airway and cardiac effects were assessed by measurement of maximal change in ple...
Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Weiss NS, Larson EB, Rosendaal FR, Psaty BM.Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk. The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds. Objective: To compare risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users, and nonusers. Methods: This population-based, case-control study was conducted at a large health maintenance organization in Washington State. Cases were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first v...
Weese JS, Anderson ME, Lowe A, Monteith GJ.This study was designed to evaluate whether Lactobacillus rhamnosus strain GG (LGG), an extensively studied probiotic organism in humans, can colonize the intestines of adult horses and foals. Lactobacillus rhamnosus strain GG was administered to adult horses at doses of 1 x 10(9) CFU/50kg bodyweight (BW)/day (group 1, 7 horses), 1 x 10(10) colony forming units/ 50kg BW/day (group 2, 7 horses) and 5 x 10(10) colony forming units/50kg BW/day (group 3, 7 horses) for 5 d. Foals received 2 x 10(10) colony forming units/50kg BW/day (group 1, 7 foals) or 1 x 10(11) colony forming units/50kg BW/day (...
Orsini JA, Spencer PA.A dose-response study was undertaken of the effects of a newly developed histamine type 2 receptor antagonist, BMY-26539-01, on gastric acid secretion in 4 fasted horses. Doses of 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, or placebo were administered in a randomly assigned treatment sequence. Hydrogen ion concentration and pH were variable during baseline measurements in all 4 animals; however, following BMY-26539-01 administration, mean pH increased and hydrogen ion concentration decreased in a dose-related pattern. At the 0.3 mg/kg and 0.5 mg/kg dose levels, pH remained elevated for > 4 h and >...
Gutjahr S, Paccamonti DL, Pycock JF, Taverne MA, Dieleman SJ, van der Weijden GC.To determine the effect of dose and day of oxytocin treatment on intrauterine pressure, 6 normal mares were treated with 10 or 25 IU oxytocin 2 days before ovulation, on the day of ovulation and 2 days after ovulation. Intrauterine pressure (IUP) was measured using micro-tip-catheters (one placed intrauterine, a second and third serving as reference sensors in the vagina and external to the mare) and transmitted by telemetry for 30 min to establish a baseline before saline was administered, iv, and for an additional 30 min after saline administration. Oxytocin was then given, iv, and IUP was r...
Steffey EP, Pascoe PJ, Woliner MJ, Berryman ER.To quantitate dose- and time-related anesthetic-sparing effects of xylazine hydrochloride (XYL) during isoflurane-induced anesthesia in horses and to characterize selected physiologic responses of anesthetized horses to administration of XYL. Methods: 6 healthy adult horses. Methods: Horses were anesthetized 2 times to determine the minimum alveolar concentration (MAC) of isoflurane in O2 and to characterize the anesthetic-sparing effect (MAC reduction) after IV administration of XYL (0.5 and 1 mg/kg of body weight, random order). Selected measures of cardiopulmonary function, blood glucose co...
John HA, Marrs J, Laffling AJ.In the autonomic nervous system (ANS) of equine grass sickness (GS) cases, some neurones show abnormal changes while neighbouring neurones are unaffected. To test whether noradrenergic neurones showed variable susceptibility to the GS toxin in culture, clonally-derived populations isolated from the same fetal thoracic sympathetic chain ganglion were challenged with plasma from GS cases previously shown to induce ANS damage when injected into normal horses. During the early stages of exposure to toxic plasma, cells within a clonal population showed variable susceptibility ranging from no obviou...
Beluche LA, Bertone AL, Anderson DE, Kohn CW, Weisbrode SE.To determine whether enrofloxacin has detrimental, dose-dependent effects on equine articular cartilage in vitro. Methods: Cartilage explants were developed from 6 healthy horses between 0 and 96 months old. Methods: Patellar cartilage explants were incubated in 5 concentrations of enrofloxacin (2 microg/ml, 10 microg/ml, 1,000 microg/ml, 10,000 microg/ml, and 50,000 microg/ml) for 72 hours. Proteoglycan synthesis (Na35SO4 incorporation for 24 hours), proteoglycan degradation (Na35SO4 release for 72 hours), endogenous proteoglycan content (dimethylmethlene blue assay), and total protein conten...
Jolly WT, Whittem T, Jolly AC, Firth EC.The dose-related effects of phenylbutazone and Depo-Medrol on chondrocyte viability and chondrocyte-mediated synthesis and depletion of proteoglycans were investigated using cultured explants of equine middle carpal joint articular cartilage. Explants from 12 horses (941 x 3 mm diameter) were cultured for a total of 5 days, which included 3 days' exposure to either phenylbutazone (0, 2, 20, 200 or 2000 micrograms/mL) or Depo-Medrol (0, 20, 200 or 2000 micrograms/mL). For each explant, amino sugar content was used as a measure of proteoglycan content, 35S incorporation as a measure of the rate ...
McCann ME, Watson TD, Boudinot FD, Moore JN.We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination...
Mills PC, Ng JC, Seawright AA, Auer DE.Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (125I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of e...
Marquardt J, Heymer J, Heinz H, Adolf GR, Deegen E.Recombinant equine interferon-beta 1 (reqIFN-beta 1) induces an antiviral state in blood mononuclear cells (BMC) of horses. Maximal protection against replication of vesicular stomatitis virus is achieved 6 hours after treatment with IFN in vitro and in vivo. Duration of the protective effect depends on the dose of IFN in vitro and in vivo. Availability of reqIFN-beta 1 in cultures of BMC for up to 48 hours does not prolong the antiviral state. The protective effect on BMC after treatment with IFN has similar duration in vivo and in vitro. Monitoring of the effect of IFN in vivo is, thus, simp...
Ensink JM, Barneveld A, Klein WR, van Miert AS, Vulto AG.The plasma disposition of ampicillin after intravenous administration at a dose rate of 15 mg/kg was studied in six healthy, 1-month-old foals. The oral bioavailability of pivampicillin was determined in the same foals at four ages, ranging from 11 days to 4 months. Pivampicillin was administered orally at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 12 hours after administration. After intravenous administration, the mean distribution and elimination half-lives of ampicillin were 0.121 and...
Goetz TE, Manohar M, Nganwa D, Gustafson R.The effects of 1.1, 1.5 and 1.8 MAC (minimum alveolar concentration) isoflurane-02 anaesthesia on skeletal muscle blood flow, 02 delivery and vascular resistance were studied in the non-dependent region of seven healthy normothermic, isocapnoeic ponies. Muscle blood flow was determined with 15 microns diameter radionuclide labelled microspheres that were injected into the left ventricle. Muscle blood flow during anaesthesia was compared to unanaesthetised (control) measurements. Isoflurane administration caused a dose dependent decrease in mean aortic pressure, and skeletal muscle (temporalis,...
Kamerling SG, Cravens WM, Bagwell CA.1. Detomidine is a novel veterinary sedative analgesic which is thought to act by stimulation of alpha 2 adrenoreceptors. The present study was undertaken to determine the direction, time course, and dose-response relationship of detomidine on specific autonomic responses in the unanaesthetized horse. 2. Detomidine was administered intravenously to eight adult thoroughbred racehorses at doses of 0.010-0.040 mg kg-1, according to a double-blind Latin square crossover design. Cardiac and respiratory rates, pupil diameter and rectal temperature were monitored for 180 min postinjection. 3. Detomid...
Dodman NH, Shuster L, Court MH, Patel J.Nalmefene, an opioid antagonist, caused a decrease in self-mutilative behavior in a 500-kg stallion. Self-mutilative attempts were counted during a control period and on 4 subsequent occasions after the IM administration of 100 mg, 200 mg, 400 mg, or 800 mg of nalmefene. The frequency of self-mutilation decreased with increasing doses of nalmefene and was virtually abolished with the 800-mg dose.
Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Weiss NS, Larson EB, Rosendaal FR, Psaty BM.Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk. The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds. Objective: To compare risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users, and nonusers. Methods: This population-based, case-control study was conducted at a large health maintenance organization in Washington State. Cases were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first v...
Weese JS, Anderson ME, Lowe A, Monteith GJ.This study was designed to evaluate whether Lactobacillus rhamnosus strain GG (LGG), an extensively studied probiotic organism in humans, can colonize the intestines of adult horses and foals. Lactobacillus rhamnosus strain GG was administered to adult horses at doses of 1 x 10(9) CFU/50kg bodyweight (BW)/day (group 1, 7 horses), 1 x 10(10) colony forming units/ 50kg BW/day (group 2, 7 horses) and 5 x 10(10) colony forming units/50kg BW/day (group 3, 7 horses) for 5 d. Foals received 2 x 10(10) colony forming units/50kg BW/day (group 1, 7 foals) or 1 x 10(11) colony forming units/50kg BW/day (...
Mattison DR, White NB, Nightingale MR.The polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BP) reduced the fertility of DBA/2N mice in a dose-dependent fashion. Control mice produced offspring at a rate of 0.91 pups/mouse per week. Treatment with BP at doses of 10, 100, 200, and 500 mg/kg decreased offspring production rates to 0.61, 0.20, zero and zero pups/mouse per week, respectively. BP also destroyed primordial oocytes in similarly treated mice. Treatment with BP at doses of 10, 50, 100, and 500 mg/kg destroyed 20%, 58%, 88%, and 100%, respectively, of the primordial oocytes in DBA/2N mouse ovaries. Dose-response curves ...
Thurmon JC, Steffey EP, Zinkl JG, Woliner M, Howland D.Xylazine given IV at doses of 0.5, 1.0, and 1.5 mg/kg to mares caused a significant (P less than 0.05) dose-related increase in serum glucose concentration and urine volume. Serum glucose concentrations as much as 150 mg/dl were recorded in mares after they were given the largest xylazine dose. The greatest urine volume, similar to changes in peak glucose concentration, always occurred during the first hour after dosing with xylazine and averaged 1.82, 3.93, and 5.68 ml/kg/hour after the 0.5-, 1.0-, and 1.5-mg/kg doses, respectively, were given. Urine osmolality and specific gravity were signi...
Cruz FS, Carregaro AB, Machado M, Antonow RR.This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min ...
Beluche LA, Bertone AL, Anderson DE, Kohn CW, Weisbrode SE.To determine whether enrofloxacin has detrimental, dose-dependent effects on equine articular cartilage in vitro. Methods: Cartilage explants were developed from 6 healthy horses between 0 and 96 months old. Methods: Patellar cartilage explants were incubated in 5 concentrations of enrofloxacin (2 microg/ml, 10 microg/ml, 1,000 microg/ml, 10,000 microg/ml, and 50,000 microg/ml) for 72 hours. Proteoglycan synthesis (Na35SO4 incorporation for 24 hours), proteoglycan degradation (Na35SO4 release for 72 hours), endogenous proteoglycan content (dimethylmethlene blue assay), and total protein conten...
Steffey EP, Pascoe PJ, Woliner MJ, Berryman ER.To quantitate dose- and time-related anesthetic-sparing effects of xylazine hydrochloride (XYL) during isoflurane-induced anesthesia in horses and to characterize selected physiologic responses of anesthetized horses to administration of XYL. Methods: 6 healthy adult horses. Methods: Horses were anesthetized 2 times to determine the minimum alveolar concentration (MAC) of isoflurane in O2 and to characterize the anesthetic-sparing effect (MAC reduction) after IV administration of XYL (0.5 and 1 mg/kg of body weight, random order). Selected measures of cardiopulmonary function, blood glucose co...
Klein L, Hopkins J.4-Aminopyridine was administered in incremental IV doses to healthy horses to evaluate cardiorespiratory and behavioral effects. Doses of 100 micrograms/kg produced apparent sensory discomfort, manifested by wiggling or curling of the lips and tongue, arching or stretching the neck, snorting, squealing, and coughing. At cumulative dosages of 300 to 500 micrograms/kg, muscle tremors, a stilted gait, and signs of excitement occurred. Once signs of excitement occurred, additional administration of 4-aminopyridine resulted in prolonged excitement consisting of severe muscle tremors and exaggerated...
Kamerling SG, DeQuick DJ, Weckman TJ, Tobin T.The dose-related effects of intravenously administered fentanyl (0.010, 0.005, 0.0025 mg/kg) and saline were studied in mature performance horses using a rigorous experimental protocol. Fentanyl produced a dose-related prolongation of the skin twitch reflex latency but did not increase the hoof withdrawal reflex latency. Dose related increases in stepping frequency, cardiac and respiratory rats were observed following fentanyl, while changes in rectal temperature and pupil area were not. These data indicate that fentanyl, a prototypic mu-agonist, produces a syndrome characterized by analgesia,...
Jolly WT, Whittem T, Jolly AC, Firth EC.The dose-related effects of phenylbutazone and Depo-Medrol on chondrocyte viability and chondrocyte-mediated synthesis and depletion of proteoglycans were investigated using cultured explants of equine middle carpal joint articular cartilage. Explants from 12 horses (941 x 3 mm diameter) were cultured for a total of 5 days, which included 3 days' exposure to either phenylbutazone (0, 2, 20, 200 or 2000 micrograms/mL) or Depo-Medrol (0, 20, 200 or 2000 micrograms/mL). For each explant, amino sugar content was used as a measure of proteoglycan content, 35S incorporation as a measure of the rate ...
Kamerling SG, Dequick DJ, Weckman TJ, Tobin T.Sensitive methods for measuring the analgesic, physiological and behavioural effects of opioids in the horse have recently been developed. Fentanyl, a prototypic mu-opiate receptor agonist, has been previously shown to produce a syndrome characterized by marked analgesia and locomotor stimulation as well as tachycardia, tachypnoea and behavioural arousal. To determine whether other opiate receptors mediate some of the actions of the narcotic analgesics in the horse, an agent with activity at kappa- and to lesser extent mu-receptors was studied using a vigorous experimental protocol. Like fenta...
Stefanski A, Mevissen M, Möller AM, Kuehni-Boghenbor K, Schmitz A.In this study, we established cell culture conditions for primary equine hepatocytes allowing cytochrome P450 enzyme (CYP) induction experiments. Hepatocytes were isolated after a modified method of Bakala et al. (2003) and cultivated on collagen I coated plates. Three different media were compared for their influence on morphology, viability and CYP activity of the hepatocytes. CYP activity was evaluated with the fluorescent substrate 7-benzyloxy-4-trifluoromethylcoumarin. Induction experiments were carried out with rifampicin, dexamethasone or phenobarbital. Concentration-response curves for...
Goetz TE, Manohar M, Nganwa D, Gustafson R.The effects of 1.1, 1.5 and 1.8 MAC (minimum alveolar concentration) isoflurane-02 anaesthesia on skeletal muscle blood flow, 02 delivery and vascular resistance were studied in the non-dependent region of seven healthy normothermic, isocapnoeic ponies. Muscle blood flow was determined with 15 microns diameter radionuclide labelled microspheres that were injected into the left ventricle. Muscle blood flow during anaesthesia was compared to unanaesthetised (control) measurements. Isoflurane administration caused a dose dependent decrease in mean aortic pressure, and skeletal muscle (temporalis,...
Alvarado TD, Elghandour MMMY, Ekanem NJ, Alcala-Canto Y, Velázquez AE, Pacheco EBF, Purba RAP, Salem AZM.The present study was conducted to investigate the aqueous extracts of Azadirachta indica (AZN), Cnidoscolus angustidens (CNA), and their combination (MIX) at dosages of 0-, 0.6-, 1.2-, and 1.8- mL for their ability to reduce greenhouse gases and fermentation profiles in an in vitro study using horse feces and a nutrient-dense diet (as substrate). The quantity of greenhouse gas and fermentation profiles were determined in in vitro incubation for 48 h. Extracts of AZN, CNA, and MIX reduced total gas production of the incubated and degraded substrates in a dose-dependent and time-dependent manne...
Sykes BW, Underwood C, McGowan CM, Mills PC.This study aimed to investigate the effect of diet and dose on the pharmacokinetics of omeprazole in the horse. Six horses received two doses (1 and 4 mg/kg) of omeprazole orally once daily for 5 days. Each dose was evaluated during feeding either a high-grain/low-fibre (HG/LF) diet or an ad libitum hay (HAY) diet in a four-way crossover design. Plasma samples were collected for pharmacokinetic analysis on days 1 and 5. Plasma omeprazole concentrations were determined by ultra-high pressure liquid chromatography-mass spectrometry. In horses being fed the HG/LF diet, on day 1, the area under...
Love DN, Rose RJ, Martin IC, Bailey M.Amoxycillin trihydrate was administered orally to 6 foals at dose rates of 13 mg/kg (low), 20 mg/kg (medium) and 30 mg/kg (high) and serum concentrations determined at intervals up to 8 h. Therapeutic serum levels of 1 microgram/ml persisted for 268 mins at a dose rate of 13 mg/kg, for 339 mins at 20 mg/kg and for 381 mins at 30 mg/kg. A 2 micrograms/ml serum level persisted for 198 mins at a dose rate of 13 mg/kg, for 268 mins at 20 mg/kg and for 311 mins at 30 mg/kg. To determine the spectra of its antibacterial activity, the minimum inhibitory concentrations of amoxycillin against 8 genera ...
Gutjahr S, Paccamonti DL, Pycock JF, Taverne MA, Dieleman SJ, van der Weijden GC.To determine the effect of dose and day of oxytocin treatment on intrauterine pressure, 6 normal mares were treated with 10 or 25 IU oxytocin 2 days before ovulation, on the day of ovulation and 2 days after ovulation. Intrauterine pressure (IUP) was measured using micro-tip-catheters (one placed intrauterine, a second and third serving as reference sensors in the vagina and external to the mare) and transmitted by telemetry for 30 min to establish a baseline before saline was administered, iv, and for an additional 30 min after saline administration. Oxytocin was then given, iv, and IUP was r...
John HA, Marrs J, Laffling AJ.In the autonomic nervous system (ANS) of equine grass sickness (GS) cases, some neurones show abnormal changes while neighbouring neurones are unaffected. To test whether noradrenergic neurones showed variable susceptibility to the GS toxin in culture, clonally-derived populations isolated from the same fetal thoracic sympathetic chain ganglion were challenged with plasma from GS cases previously shown to induce ANS damage when injected into normal horses. During the early stages of exposure to toxic plasma, cells within a clonal population showed variable susceptibility ranging from no obviou...
Boly R, Dessy S, Kohnen S, Kini F, Lompo M, Mouithys-Mickalad A, Guissou IP, Dubois J, Deby-Dupont G, Serteyn D, Franck T.Agelanthus dodoneifolius DC Danser (Loranthaceae) is used for the treatment of various diseases including asthma. The aqueous and hydroalcoholic extracts have been reported to have anti-inflammatory, spasmolytic and bronchorelaxant activities. The present study investigates the effects of the aqueous decoction and the diethyl ether, ethyl acetate and butanolic fractions of Agelanthus dodoneifolius DC Danser (Loranthaceae) on reactive oxygen species (ROS) production and myeloperoxidase (MPO) release by phorbol 12-myristate 13-acetate (PMA)-stimulated equine neutrophils and on purified equine MP...
Orsini JA, Spencer PA.A dose-response study was undertaken of the effects of a newly developed histamine type 2 receptor antagonist, BMY-26539-01, on gastric acid secretion in 4 fasted horses. Doses of 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, or placebo were administered in a randomly assigned treatment sequence. Hydrogen ion concentration and pH were variable during baseline measurements in all 4 animals; however, following BMY-26539-01 administration, mean pH increased and hydrogen ion concentration decreased in a dose-related pattern. At the 0.3 mg/kg and 0.5 mg/kg dose levels, pH remained elevated for > 4 h and >...
Dodman NH, Shuster L, Court MH, Patel J.Nalmefene, an opioid antagonist, caused a decrease in self-mutilative behavior in a 500-kg stallion. Self-mutilative attempts were counted during a control period and on 4 subsequent occasions after the IM administration of 100 mg, 200 mg, 400 mg, or 800 mg of nalmefene. The frequency of self-mutilation decreased with increasing doses of nalmefene and was virtually abolished with the 800-mg dose.
Camargo FC, Robinson NE, Berney C, Eberhart S, Baker S, Detolve P, Derksen FJ, Lehner AF, Hughes C, Tobin T.The bronchodilator effects of trimetoquinol (TMQ) have been studied when administered i.v. or intratracheally, but not in an aerosolised form. Objective: To define the relationship between the therapeutic and adverse responses (therapeutic index) of TMQ when administered as an aerosol or by the oral route. Methods: Increasing doses of TMQ were administered to horses with heaves as an aerosol and by the oral route. Dose ranged 100-1000 microg/horse for aerosolised TMQ and from 6-60 microg/kg bwt for the oral route. Airway and cardiac effects were assessed by measurement of maximal change in ple...
Burton AJ, Giguère S, Warner L, Alhamhoom Y, Arnold RD.Therapeutic drug monitoring in a small number of foals of various ages indicates that the standard adult dose of 6.6 mg/kg bwt q. 24 h for gentamicin is too low and a dose of 12 mg/kg bwt has been proposed. The pharmacokinetics of this dosage in foals and the ages at which this higher dose should be used have not previously been investigated. Objective: To determine the effect of age on the pharmacokinetics of a single 12 mg/kg bwt i.v. dose of gentamicin in foals. Methods: Six healthy foals were given a single i.v. dose of gentamicin at 1-3 days, 2, 4, 8 and 12 weeks of age. Plasma concentrat...
Cuervo-Arango J, Newcombe JR.The objective of this study was to establish and characterize the relationship between the dose of cloprostenol (37.5, 250, 500 and 750 μg) and the age of the early corpus luteum (CL) (80, 88, 96, 104 and 112 h) on the luteolytic response of mares. Behavioural oestrus and ultrasonographic signs of return to oestrus were considered as the occurrence of full luteolysis. A total of 298 mares were divided into groups according to dose of cloprostenol and CL age. There was an effect of dose of cloprostenol (p < 0.001) and age of the CL at the time of treatment (p 0.05); and that of 500 similar...
Muir WW, Sams RA, Huffman R.The acute behavioral cardiopulmonary and pharmacokinetic effects of propoxyphene hydrochloride were studied in seven adult horses. Each horse was given three different dosages of propoxyphene (0.5, 1.0, 2.2 mg/kg) IV. Fourteen days was allotted between each drug administration. The lower IV dosages of propoxyphene (0.5, 1.0 mg/kg) resulted in no changes in indices of cardiopulmonary function. Four horses demonstrated a transient period of muscle fasciculations when given 0.5 mg of propoxyphene/kg. Horses given 1.0 mg/kg demonstrated a brief period of euphoria, ataxia, and muscle fasciculations...
Mills PC, Ng JC, Seawright AA, Auer DE.Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (125I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of e...
Verberne LR, Mirck MH.The toxicity of parbendazole in different doses was investigated with 52 horses and 16 ponies, in twelve groups. Side effects observed with the anthelmintic were laxation (soft dung, diarrhoea), anorexia, and listlessness. The seriousness of these symptoms depended greatly on the dose used. Half the therapeutic dose of parbendazole (2.5 to 3.75 mg/kg) administered on two consecutive days led, as a rule, to only slight toxic symptoms and proved highly effective with regard to gastro-intestinal nematodes occurring in horses and ponies. The utilisation of "standard powders" (not commercially avai...
Sasaki N, Tsuzuki N, Yamada M, Minami T, Yamada H.This study aimed to establish a standard dose and sample collection time for (13)C phenylalanine and (13)C-Dipeptide breath test in horses. To evaluate dose-dependent effects, healthy horses received 2.5 mg/kg, 5 mg/kg, and 10 mg/kg (13)C phenylalanine dissolved in 1 ml/kg distilled water and 1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg (13)C dipeptide dissolved in 2 ml/ kg distilled water. Tmax was observed during the sample collection time. For (13)C phenylalanine, the standard deviation of Cmax at 5 mg/kg was lower than that of 10 mg/kg. For (13)C dipeptide, the standard deviation of Tmax was the low...
Costa G, Labadia A, Garcia-Sacristan A.The effects of verapamil, a calcium antagonist agent, were studied on smooth muscle preparations of the lower urinary tract of horses. Verapamil (2 X 10(-4) to 2 X 10(-8) M) relaxed the ureter, urethra and urinary bladder preparations contracted by potassium (127 mM), L-noradrenaline (2 X 10(-5) M), histamine (2 X 10(-5) M) and acetylcholine (2 X 10(-5) M). These results allow the conclusion that verapamil has a dose-dependent relaxing effect on smooth muscle of the lower urinary tract.
Lyons ET, Drudge JH, Tolliver SC.Critical tests were conducted in 11 naturally infected horses to evaluate the anthelmintic activity of parbendazole. Single doses at the rates of 30, 20, 10, 5, or 2.5 mg/kg of body weight were administered by stomach tube to 1, 4, 2, 2, and 2 horses, respectively. Parbendazole was active against Parascaris equorum, Oxyuris equi, Strongylus vulgaris, Strongylus edentatus, and small strongyles throughout the range of doses. Generally, small numbers of P equorum were present, but apparently a dose rate higher than 2.5 mg/kg is necessary for complete clearance. Removal of O equi was virtually 100...
