Effect of phenylbutazone on the haemodynamic, acid-base and eicosanoid responses of horses to sustained submaximal exertion     

K.W. Hinchcliff  K.H. McKeever  W.W. Muir III 《Research in veterinary science》1994,56(3):352

The systemic haemodynamic and acid-base effects of the administration of phenylbutazone (4·4 mg kg⁻¹ intravenously) to standing and running horses were investigated. Phenylbutazone, or a placebo, was administered to each of six mares either 15 minutes before, or after 30 minutes of a 60-minute submaximal exercise test which elicited heart rates approximately 55 per cent of maximal, and to the same horses at rest. The variables examined included the cardiac output, heart rate, systemic and pulmonary arterial pressures, right atrial and right ventricular pressures, and arterial and mixed venous blood gases and pH. Serum sodium, potassium and chloride concentrations, and plasma thromboxane B₂, 6-keto-prostaglandin F_1α (6-keto-PGF_1α), and prostaglandin E₂ (PGE₂) concentrations were measured in separate studies using similar protocols in the same horses. Running produced increases in heart rate, cardiac output, mean arterial and right ventricular pressure, and decreases in total peripheral resistance. The acid:base responses to exertion were characterised by respiratory alkalosis. Exertion did not significantly influence plasma 6-keto-PGF_1α or PGE₂ concentrations but plasma thromboxane B₂ concentrations were increased significantly by 60 minutes of exertion in the untreated horses. This exercise-induced increase in plasma thromboxane B₂ concentration was inhibited by the previous administration of phenylbutazone, but phenylbutazone did not produce detectable changes in systemic haemodynamic or acid-base variables in either standing or running horses.  相似文献   

Immunisation of cattle against heartwater by infection with Cowdria ruminantium elicits T lymphocytes that recognise major antigenic proteins 1 and 2 of the agent     

Mwangi DM  McKeever DJ  Nyanjui JK  Barbet AF  Mahan SM 《Veterinary immunology and immunopathology》2002,85(1-2):23-32

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Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein     

Ferguson AD  McKeever BM  Xu S  Wisniewski D  Miller DK  Yamin TT  Spencer RH  Chu L  Ujjainwalla F  Cunningham BR  Evans JF  Becker JW 《Science (New York, N.Y.)》2007,317(5837):510-512

Leukotrienes are proinflammatory products of arachidonic acid oxidation by 5-lipoxygenase that have been shown to be involved in respiratory and cardiovascular diseases. The integral membrane protein FLAP is essential for leukotriene biosynthesis. We describe the x-ray crystal structures of human FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0 and 4.2 angstrom resolution, respectively. The structures show that inhibitors bind in membrane-embedded pockets of FLAP, which suggests how these inhibitors prevent arachidonic acid from binding to FLAP and subsequently being transferred to 5-lipoxygenase, thereby preventing leukotriene biosynthesis. This structural information provides a platform for the development of therapeutics for respiratory and cardiovascular diseases.  相似文献   

Immunopathology of Chlamydophila abortus infection in sheep and mice   总被引：3，自引：0，他引：3  

Kerr K  Entrican G  McKeever D  Longbottom D 《Research in veterinary science》2005,78(1):1-7

Chlamydophila abortus targets the placenta, causing tissue damage, inflammation and abortion (enzootic abortion of ewes). It is one of the main infectious causes of abortion in ewes, resulting in major economic losses to agricultural industries worldwide. Although ruminants and pigs are the principal hosts, humans are also susceptible to infection. Control of disease requires a host inflammatory response, which is likely to contribute to pathology and abortion. Mouse models have been widely used to provide insight into the role of specific immune cells in controlling infection and disease. The use of such model systems for investigating the mechanisms of abortion, latency, persistence, and immunity to reinfection will result in the identification of novel vaccine control strategies for sheep.  相似文献   

Effect of chronic clenbuterol administration and exercise training on immune function in horses     

Malinowski K  Kearns CF  Guirnalda PD  Roegner V  McKeever KH 《Journal of animal science》2004,82(12):3500-3507

Effects of longitudinal exercise training and acute intensive exercise (simulated race test) on immune function have not been reported in horses. Clenbuterol, a beta2-adrenergic agonist, is used to manage inflammatory airway disease in horses. This study investigated the interaction of 8 wk of exercise training with or without 12 wk of clenbuterol administration in horses. Twenty-three untrained standardbred mares (10 +/- 3 yr, Mean +/- SE) were used and divided into four experimental groups. Horses given clenbuterol plus exercise (CLENEX; n = 6) and clenbuterol alone (CLEN; n = 6) received 2.4 microg/kg BW of clenbuterol twice daily (in an average volume of 20 mL) on a schedule of 5 d on and 2 d off for 12 wk. The CLENEX group was also aerobically trained 3 d/wk. Mares given exercise alone (EX; n = 5) were aerobically trained for 3 d/wk, and the control group (CON; n = 6) remained sedentary. Both EX and CON horses were administered similar volumes (approximately 20 mL) of molasses twice daily. A simulated race test (SRT) resulted in an elevation in lymphocyte number postexercise (P < 0.05). There was no significant difference after acute exercise in either monocyte or granulocyte number. Acute exercise resulted in a decrease (P < 0.05) in the percentage of CD4+ and an increase (P < 0.05) in the percentage of CD8+ cells. The SRT resulted in a decreased lymphoproliferative response to pokeweed mitogen (P < 0.05). A SRT had no effect on antibody production in response to equine influenza vaccine. The EX group demonstrated greater cortisol concentrations at rest and at all other time points postexercise after completing the training regimen compared with CLENEX horses (P < 0.05). Preexercise (SRT) peripheral blood monocyte number was lower in CLENEX horses than in other treatment groups (P < 0.05). Clenbuterol and exercise training did not significantly affect post-SRT changes in leukocyte numbers. Exercise training resulted in a decrease (P < 0.05) in the percentage of CD8+ cells post-SRT compared with other groups, but the percentage of CD4+ cells was not altered by either clenbuterol or exercise conditioning. Lymphocyte proliferative response was not affected by clenbuterol or exercise treatment. Horses demonstrated responses to bouts of acute exercise as noted with other species, namely humans and rodents.  相似文献   

Myosin heavy chain profiles and body composition are different in old versus young Standardbred mares   总被引：2，自引：0，他引：2  

Lehnhard RA  McKeever KH  Kearns CF  Beekley MD 《Veterinary journal (London, England : 1997)》2004,167(1):59-66

There are limited data on age-related changes in body composition or skeletal muscle in the horse. Therefore, the purpose of this study was to investigate any differences in muscle myosin heavy chain (MHC) and body composition associated with aging. Twenty-three young (4-8 years) and eight old (20+ years) unfit Standardbred mares were evaluated. Rump fat thickness was measured using B-mode ultrasound and per cent body fat (% fat) was calculated. Needle muscle biopsies were obtained from right gluteus medius muscle. MHC composition was determined via sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Three MHC isoforms were subsequently identified as type I, type IIA, and type IIX and quantified using a scanning and densometric system. There were no significant differences (p>0.05) between old and young mares in fat (%) (19.0+/-6.4 vs 20.5+/-5.4), fat mass (kg) (102.3+/-39.9 vs 106.9+/-37.1), or body weight (kg) (529.4+/-34.9 vs 512.7+/-57.7). However, the old mares had significantly (p<0.05) greater lean body mass than the young mares (427.1+/-24.5 vs 405.7+/-37.9). Aged mares had significantly (p<0.05) less type I (7.8+/-2.9% vs 12.1+/-4.4%) and IIA (27.8+/-7.1% vs 36.1+/-9.5%) fibres than the young group but more type IIX (64.6+/-4.7% vs 51.8+/-11.1%). The MHC data are consistent with the age-related changes seen in other species.  相似文献   

East Coast fever immunisation field trial in crossbred dairy cattle in Hanang and Handeni districts in northern Tanzania     

Lynen G  Yrjö-Koskinen AE  Bakuname C  Di Giulio G  Mlinga N  Khama I  Hanks J  Taylor NM  James AD  McKeever D  Peters AR  Rushton J 《Tropical animal health and production》2012,44(3):567-572

East Coast fever (ECF) causes considerable mortality and production losses in the Tanzania smallholder dairy sector and limits the introduction of improved dairy breeds in areas where the disease is present. The infection and treatment method (ITM) was adopted by smallholder dairy farms for ECF immunisation in Hanang and Handeni districts of Tanzania. This study recorded incidence rates for ECF and other tick-borne diseases (TBDs) for ECF-immunised and non-immunised cattle between 1997 and 2000. Approximately 80% of smallholder households from both sites (n?=?167) participated in this longitudinal study, with immunisations carried out at the request of the livestock owners. Efficacy of ITM for preventing ECF cases in these crossbred dairy cattle was estimated at 97.6%, while that for preventing ECF deaths was 97.9%. One percent of the cattle developed clinical ECF as a result of immunisation. Since ECF immunisation permits a reduction in acaricide use, an increase in other TBDs is a potential concern. Sixty-three percent of farmers continued to use the same acaricide after immunisation, with 80% of these reducing the frequency of applications. Overall, 78% of farmers increased the acaricide application interval after immunisation beyond that recommended by the manufacturer, resulting in annual savings in the region of USD 4.77 per animal. No statistical difference was observed between the immunised and non-immunised animals in the incidence of non-ECF TBDs. However, immunised animals that succumbed to these diseases showed fewer case fatalities. ITM would therefore appear to be a suitable method for ECF control in Tanzania's smallholder dairy sector.  相似文献   

Overtraining syndrome in standardbred horses: new insights into the role of red blood cell hypervolaemia     

McKeever KH 《Veterinary journal (London, England : 1997)》2003,165(3):190-192

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Response to Cortisol Stimulation Tests in Old vs. Young Standardbred Mares     

N.R. LiburtK.H. McKeever  E.K. Wunderlich 《Journal of Equine Veterinary Science》2009

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Bovine CD4+ T-cells lines reactive with soluble and membrane antigens of Cowdria ruminantium.     

P. Tott    J. Nyanjui  A. Bensaid  D. McKeever 《Veterinary immunology and immunopathology》1999,70(3-4):269-276

Cowdria-specific CD4⁺ T-cell lines generated from immunised cattle respond to both soluble and membrane proteins of the agent. Furthermore, the lines produced the Cowdria-inhibitory cytokine IFN-γ in response to soluble antigens fractionated by gel filtration and FPLC. Activity eluted as a single peak around fraction 15 for all T-cell lines tested. This fraction induced the highest production of IFN-γ by the lines and was shown by SDS-polyacrylamide gel electrophoresis and silver staining analysis to contain less than 10 different bands ranging from 22 to 32 kDa. Given their high sensitivity and specificity, these short-term CD4⁺ T-cell lines will be valuable tools for the identification of Cowdria antigens for incorporation in a subunit vaccine.  相似文献