bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide inhibits aggrecan degradation in explant cultures of equine articular cartilage
Authors: Bird J. L. E. , May S. , Bayliss M. T. 
Published: April 2007

SummaryArthroses are debilitating diseases of articular joints which result in erosion of the cartilage extracellular matrix. Nitric oxide (NO) is a major component of the inflammatory response, and has been implicated as a mediator of some of the effects of the proinflammatory cytokine, interleukin‐1 (IL‐1). In this study, we investigated the role of NO in the regulation of proteoglycan degradation in equine articular cartilage. NO fully mediated the suppressive effect of IL‐1 on proteoglycan synthesis. However, NO was also antagonistic to proteoglycan degradation, irrespective of whether degradation was initiated by 10 ng/ml IL‐1 or 1 μmol/l all‐trans retinoic acid (RA) which (unlike IL‐1) does not elevate NO production. This was confirmed using the NO donor 2,2′‐(hydroxynitrosohydrazono) bis‐ethanamine (DETA‐NONOate) and the iNOS inhibitorL‐N5‐iminoethyl ornithine (dihydrochloride) (L‐NIO). The G1 fragments of aggrecan were detected in the media and extracts of cartilage explant cultures treated with all‐trans RA, DETA‐NONOate and L‐NIO. The presence of exogenous NO in culture resulted in a decrease in the appearance of the ‘aggrecanase’ cleavage epitope. Therefore, changes in the appearance of the G1 fragment expressing the ‘aggrecanase’ cleavage epitope in the media emulated the glycosaminoglycan loss from the tissue. These results lend further support to the hypothesis that NO has an anticatabolic role in equine cartilage proteoglycan degradation, and suggest that this may be mediated by the regulation of ‘aggrecanase’ activity. Therefore, any pharmacological intervention using NO as a target must take into account both its catabolic and anticatabolic roles in joint tissue turnover.
Assessment of muscle oxygenation in the horse by near infrared spectroscopy
Authors: Pringle J. , Roberts C. , Tatianaart C. , Lekeux P. 
Published: April 2007

SummaryThis study examined the ability of nearinfrared spectroscopy (NIRS) to noninvasively determine changes to muscle oxygenation in the resting horse. Five horses had (NIRS) performed over extremity muscle while under general anaesthesia, first with 8 min limb ischaemia, then systemic hypoxaemia for 5 min. A second group of 6 awake horses had NIRS performed over extremity muscle while being administered hypoxic gas (F1O2 0.10) for 5 min, and after return to steady state, limb ischaemia was induced for an additional 5 min. In the anaesthetised horses' ischaemia induced marked and significant muscle deoxygenation of haemoglobin/myoglobin (P<0.01), with corresponding arterial saturation decreasing from 98.9 to 81.9%. Hypoxaemia induced small yet significant muscle deoxygenation (P<0.01) that was 3.2% of the ischaemia deoxygenation signal, with a corresponding decrease in arterial saturation from 98.6 to 90.4%. In the awake horses muscle deoxygenation was not detectable during hypoxia despite reduction of arterial saturation from 97.8 to 86.8%, whereas ischaemia induced rapid and significant deoxygenation of muscle (P<0.05), with corresponding reduction of venous saturation from 78.4 to 75.4%. In neither group of horses was there evidence of cytochrome aa3 reduction, despite complete ischaemia forup to 8 min. NIRS changes in the resting horse muscle clearly differed between ischaemia and hypoxaemia, and can readily show muscle deoxygenation in clinically relevant hypoxaemia in the horse under anaesthesia. Further, as the deoxygenation signal induced by ischaemia was clearly detectable above a background movement artefact, NIRS application to study of muscle oxygenation in the working horse should be explored.
Equine carpal articular cartilage fibronectin distribution associated with training, joint location and cartilage deterioration
Authors: Murray Rachel C. , Janicke H. C. , Henson F. M. D. , Goodship A. 
Published: April 2007

SummaryProcesses involved in equine carpal osteochondral injury have not been established. In other species, fibronectin appears important in chondrocyte‐matrix interactions, and levels are increased in osteoarthritis. This investigation aimed to (a) describe fibronectin immunoreactivity in the middle carpal joint of 2‐year‐old Thoroughbreds, (b) determine topographical variations, (c) compare strenuously trained (Group 1) or gently exercised horses (Group 2) and (d) describe sites with early osteoarthritis.Group 1(n = 6) underwent a 19 week high intensity treadmill training programme.Group 2(n = 6) underwent 40 min walking until euthanasia. Dorsal and palmar sites on radial, intermediate and third carpal articular surfaces were prepared. Immunohistochemistry was performed using a biotin‐streptavidin/peroxidase method. Cross‐reactivity of rabbit antihuman fibronectin antiserum with equine fibronectin was confirmed using Western blotting. Results showed: (a) fibronectin was present primarily in pericellular and interterritorial matrix locations, (b) dorsal sites had zonal immunoreactivity compared to palmar sites, (c)Group 1dorsal radial carpal cartilage had increased superficial staining compared toGroup 2and (d) fibrillated cartilage showed increased intracellular and local matrical immunoreactivity (superficial zone). These findings suggest topographical and exercise‐related variations in fibronectin distribution, and indicate equine fibronectin is localised at sites of cartilage degeneration and released into the matrix by chondrocytes in the local area.
Postmortemfindings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924–1996)
Authors: Sandin A. , Skidell J. , Häggström J. , Nilsson G. 
Published: April 2007

SummaryThe present study was performed to estimate retrospectively the prevalence of gastric ulceration in necropsied Swedish horses and to evaluate some potential risk factors. Horses (n = 3715) olderthan age one yearand necropsied 1924–1996 were included. Information about breed, gender, age, season of death, clinical signs of colic,Gasterophiluslarvae and documentation of diseases in different organs was recorded. Data on size, number and anatomical distribution of gastric ulcers were also obtained. The cold‐blooded horses and the Standardbreds were the 2 most dominating breeds in our material. Gastric ulcers/erosions were seen in 633 (17%) of the horses. The highest prevalence was found in Thoroughbreds (19%) and Standardbreds (19%), whereas only 7% of the cold‐blooded horses were affected. The cutaneous region along themargo plicatuswas the most commonly affected area (52%). Multiple ulcers were seen in 62% of the horses with gastric ulcers and concurrent ulcers in the oesophagus were reported in 6%. In the bivariate analysis, significant associations were found between gastric ulcers and signs of colic (P<0.001) and gender (P<0.001), as well as between concomitant bowel (P<0.001), liver (P<0.05) and oesophageal (P<0.01) lesions. Using a multivariate logistic regression model, only year of necropsy and breed were found significantly to influence the risk of gastric ulceration by decreasing the Log Likelihood test value. The present study shows clearly that gastric ulceration has been present in Swedish horses throughout the 20th century, which also may be the situation worldwide.
Immunity to equine influenza: relationship of vaccine‐induced antibody in young Thoroughbred racehorses to protection against field infection with influenza A/equine‐2 viruses (H3N8)
Authors: Newton J. R. , Townsend H. G. G. , Wood J. L. N. , Sinclair R. , Hannant D. , Mumford J. A. 
Published: April 2007

SummaryField outbreaks of influenza that occurred in vaccinated Thoroughbred racehorses in Newmarket in 1995 and 1996 were investigated by nucleoprotein ELISA and serology. Investigations showed that serum levels of vaccine‐induced single radial haemolysis (SRH) antibody correlated closely with protective immunity against equine influenza and were consistent with observations made in previous experimental studies using nebulised aerosol challenge. In the second part of this study, antibody levels stimulated by vaccination were investigated to examine probable protection in high risk groups, such as yearlings and horses in training. Results for yearlings correlated closely with experimentally derived antibody profiles described for several equine influenza vaccines. The horses in training had levels of antibody immediately prior to revaccination, which were higher than those measured in the yearlings. In conclusion, SRH antibody, used in the investigation of outbreaks and surveillance of post vaccination responses, was shown to correlate with and validate experimental vaccination and challenge models currently used in ponies in the licensing of modern vaccines. There may be benefit from serological monitoring of horses following vaccination through identification of susceptible periods to infection and demonstration of poor vaccine responders. This would allow appropriate and timely amendment of vaccination strategies to maximise protective immunity against influenza.
Influence of environmental and genetic factors on allergen‐specific immunoglobulin‐E levels in sera from Lipizzan horses
Authors: EDER C. , CURIK I. , BREM G. , CRAMERI R. , BODO I. , HABE F. , LAZARY S. , SÖLKNER J. , MARTI E. 
Published: April 2007

SummaryTo investigate whether allergen‐specific IgE production is influenced by environmental and genetic factors, IgE levels against 2 mould extracts (Alternaria alternata[Alt a] andAspergillus fumigatus[Asp f]) and against recombinant (r) rAlt a 1, rAsp f 7 and rAsp f 8 were determined by ELISA in sera from 448 Lipizzan horses living in 6 studfarms.Statistical evaluation showed a significant effect of studfarm‐specific environment on IgE levels against the different allergens, but genetic factors also influenced allergen‐specific IgE production: an heritability of 0.33 was found for IgE levels against the 2 mould extracts and of 0.21 for rAsp f 8‐specific IgE. Heritability estimates for rAlt a 1‐ and rAsp f 7‐specific IgE were negligible.Investigations for a possible association between Major Histocompatibility Complex (MHC) class I antigens and specific IgE levels were carried out. The most consistent significant association was found between the equine leucocyte antigen (ELA) A8 and undetectable IgE titres against rAsp f 7 and rAsp f 8. Significant ELA associations were also demonstrated between ELAA1 and higher specific IgE levels, between ELA A14 and lower IgE levels against the mould extracts and in one studfarm between ELA Be27 and lowerAspergillus‐specific IgE levels.
The mucosal humoral immune response of the horse to infective challenge and vaccination with Equine herpesvirus‐1 antigens
Authors: BREATHNACH C. C. , YEARGAN M. R. , SHEORAN A. S. , ALLEN G. P. 
Published: April 2007

SummaryEquine herpesvirus‐1 (EHV‐1) remains a frequent cause of upper respiratory tract infection and abortion in horses worldwide. However, little is known about the local antibody response elicited in the upper airways of horses following exposure to EHV‐1. This study analysed the mucosal humoral immune response of weanling foals following experimental infection with virulent EHV‐1, or vaccination with either of 2 commercial vaccines. Twenty weanlings were assigned to 5 groups and were inoculated with, or vaccinated against, EHV‐1 following different regimens. Finally, all weanlings were simultaneously challenged intranasally with virulent EHV‐1 Army 183 (A183). Nasal wash and serum samples were collected at regular intervals until 13 weeks after final challenge. Nasal washes were assayed for EHV‐1‐specific equine IgGa, IgGb, IgG(T), IgA, IgM and total virus‐specific antibody using an indirect, quantitative ELISA. Total serum antibody responses were also monitored, and clinical signs of EHV‐disease were recorded for each individual.Virus‐specific IgA dominated the mucosal antibody response elicited in weanlings inoculated with A183, being detectable at up to 3.1 μg/mg total IgA 13 weeks after challenge. Neither inactivated EHV‐1 administered i.m., nor attenuated EHV‐1 administered intranasally induced detectable mucosal antibodies. EHV‐1‐specific mucosal antibodies impeded EHV‐1 plaque formation in vitro. Such virus‐neutralising antibody probably contributes to a reduction of shedding of EHV‐1 from the respiratory tract of virus‐infected horses.
Neutrophil functions and serum IgG in growing foals
Authors: DEMMERS S. , JOHANNISSON A. , GRÖNDAHL G. , JENSEN‐WAERN M. 
Published: April 2007

SummaryThe aim of this study was to investigate the phagocytic and killing capacities as well as expression of CD18 of neutrophils obtained from healthy foals from birth to age 8 months. Blood was taken from 6 Standardbred foals at 7 time‐points between ages 2–56 days and thereafter once a month. For comparison, cells from 16 mature horses were evaluated. Neutrophil phagocytosis of yeast cells was assessed by flow cytometry after opsonisation with mature pooled serum, autologous serum or anti‐yeast IgG. The killing capacity of the neutrophils, as indicated by the oxidative burst, was monitored by chemiluminescence. Serum IgG concentration was measured by radial immunodiffusion. In addition to clinical examination, the amount of serum amyloid A and the total leucocyte count were used as markers for infection. The phagocytic ability was impaired until age 3 weeks, when autologous serum was used as opsonin. Killing capacity was also low initially but, from 3 months onwards, chemiluminescence values were equal to or higher than in mature horses. Serum IgG decreased from 10 g/l at 2 days to 5 g/l at 2 months and then increased gradually to 10 g/l at the end of the study. These findings may in part explain the increased susceptibility to bacterial infections in young horses.
Transforming growth factor beta concentrations and interferon gamma responses in cerebrospinal fluid of horses with equine protozoal myeloencephalitis
Authors: FURR M. , PONTZER C. 
Published: April 2007

SummaryThe following experiment was performed to test the hypothesis that transforming growth factor beta (TGF‐β) concentration varies in the cerebrospinal fluid and serum of horses with EPM and to determine if cerebrospinal fluid (CSF) alters the interferon‐gamma (IFN‐γ) rersponse of equine peripheral blood mononuclear cells (PBMCs). The concentration of transforming growth factor‐beta (TGF‐β2) was investigated in the serum and cerebrospinal fluid (CSF) of 18 horses (9 normal, 9 affected with equine protozoal myeloencephalitis [EPM]). The TGF‐β2 assay was validated in a group of 6 normal horses. Intra‐assay variability was 4.7%, and interassay variability was 10.7%. The slope of the curve of the unknown samples of various volumes demonstrated parallelism with a curve developed using equal volumes of assay kit standard. Assay of normal and EPM‐affected horses found that TGF‐β2 was present in both the serum and CSF of all animals. However, the concentration of TGF‐β2 in the CSF was less (P = 0.03) in EPM‐affected horses (144 pg/ml) than in normal horses (256 pg/ml). In addition, the effect of CSF from normal and EPM‐affected horses on the production of interferon‐gamma (IFN‐γ) by PHA‐P stimulated PBMCs from normal horses was investigated using a bioassay. It was found that CSF from normal and EPM‐affected horses enhanced IFN‐γ activity from PHA‐P stimulated peripheral blood mononuclear cells (P ≤ 0.05); however, the response to CSF from EPM‐affected horses was no different than the response to CSF from normal horses. Treatment of cells with anti‐TGF‐β2 monoclonal antibodies slightly increased the response when co‐incubated with CSF from normal horses, and slightly decreased it when co‐incubated with CSF from EPM‐affected horses. These differences, however, did not achieve statistical significance (P>0.05). Results of this study indicated that production of TGF‐β2 is altered in horses with EPM, and that CSF appears to contain substances which alter the inflammatory reaction to plant lectins. These findings confirm the immunomodulatory properties of CSF and suggest new techniques for future research regarding the pathophysiology of EPM.
Exercise alters the immune response to equine influenza virus and increases susceptibility to infection
Authors: FOLSOM R. W. , LITTLEFIELD‐CHABAUD M. A. , FRENCH D. D. , POURCIAU S. S. , MISTRIC L. , HOROHOV D. W. 
Published: April 2007

SummaryEquine influenza virus remains a major health concern for the equine industry in spite of ongoing vaccination programmes. Previous work has shown that the immune system of horses can be affected by strenuous exercise. The possible adverse consequence of exercise‐induced alterations in lymphocyte responses measuredin vitrowas unknown. Here we demonstrate that subjecting vaccinated ponies to a 5 day strenuous exercise programme results in a significant suppression of their T cell‐mediated immune response to equine influenza virus as measured by decreased lymphoproliferation and gamma interferon production measuredin vitro.These same ponies also demonstrated increased susceptibility to influenza disease following a challenge exposure to the same strain of virus. Rested ponies that had received the same vaccine and challenge were completely protected from disease. Our results demonstrate that exercise‐induced suppression of the equine immune response to influenza virus can be associated with an increased susceptibility to disease.
Production of biologically active equine interleukin 12 through expression of p35, p40 and single chain IL‐12 in mammalian and baculovirus expression systems
Authors: McMONAGLE E. L. J. , TAYLOR S. , ZUILEKOM H. van , SANDERS L. , SCHOLTES N. , KEANIE L. J. , HOPKINS C. A. , LOGAN N. A. , BAIN D. , ARGYLE D. J. , ONIONS D. E. , SCHIJNS V. E. , NICOLSON L. 
Published: April 2007

SummaryInterleukin‐12 (IL‐12) is a key cytokine in the development of cell‐mediated immune responses. Bioactive IL‐12 is a heterodimeric cytokine composed of disulphide linked p35 and p40 subunits. The aim of this study was to verify biologically activity of the products expressed from equine interleukin‐12 (IL‐12) p35 and p40 cDNAs and to establish whether equine IL‐12 could be expressed as a p35/p40 fusion polypeptide, as has been reported for IL‐12a of several mammalian species. We report production of equine IL‐12 through expression of p35 and p40 subunits in mammalian and insect cells and of a p35:p40 fusion polypeptide in mammalian cells. Conditioned medium recovered from cultures transiently transfected with constructs encoding equine p35 and p40 subunits or single chain IL‐12 enhanced IFN‐γ production in cells derived from equine lymph nodes. Preincubation of IFN‐γ inducing preparations with anti‐p40 monoclonal antibody resulted in a significant decrease in IFN‐γ induction capacity. Medium recovered from p35 and p40‐expressing baculovirus infected cultures enhanced target cell IFN‐γ production and proliferation. Experimental studies in mice and other animals have revealed a therapeutic benefit of IL‐12 in cancer, inflammatory and infectious disease and an adjuvant effect in prophylactic regimes. Production of a bioactive species‐specific IL‐12 is a first step towards an investigation of its potential application in equine species.
Immunoglobulin‐E‐bearing cells in skin biopsies of horses with insect bite hypersensitivity
Authors: HAEGEN A. van der , GRIOT‐WENK M. , WELLE M. , BUSATO A. , TSCHARNER C. von , ZURBRIGGEN A. , MARTI E. 
Published: April 2007

SummaryThe aim of the present study was to investigate, with immunohistochemistry andin situhybridisation, if immunoglobulin‐E (IgE) and mast cells are involved in the pathogenesis of insect bite hypersensitivity (IBH), an allergic dermatitis of horses. In tissue sections fixed in paraformaldehyde (PFA) for <24 h, significantly more IgE protein‐bearing cells were found in the dermis and epidermis of acute and chronic IBH lesions than in skin biopsies from healthy horses (medians = 466, 236 and 110 cells/mm2, respectively; P ≤ 0.01). More IgE‐mRNA positive (+) cells were observed in the dermis of acute IBH lesions than in the dermis of healthy skin (median = 2.8 vs. 0.0 cells/mm2; P ≤ 0.01). Significantly, more mast cells were detected with metachromatic (median = 160 vs. 62 cells/mm2; P ≤ 0.001) and tryptase‐specific stainings (median = 120 vs. 69 cells/mm2; P ≤ 0.001) in the dermis of acute IBH biopsies compared to healthy skin. No chymase+ mast cells were found in any skin biopsy. IBH lesions fixed in PFA for >24 h were compared to dermatomycosis (DM) lesions; IBH biopsies contained a similar number of IgE‐protein+ cells to DM biopsies (median = 249 vs. 192 cells/mm2; P = 0.08) but had significantly more IgE‐mRNA+, metachromatic and tryptase+ mast cells than DM biopsies. This study suggests an involvement of IgE‐mediated immune reactions in the pathogenesis of IBH as well as, sometimes, in dermatomycosis. Using double labelling, cells which expressed IgE protein and contained mast cell enzymes were detected.
Intravenous pentoxifylline does not enhance the pulmonary haemodynamic efficacy of frusemide in strenuously exercising Thoroughbred horses
Authors: MANOHAR M. , GOETZ T. E. , ROTHENBAUM P. , HUMPHREY S. 
Published: April 2007

SummaryThe present study was carried out to examine whether pentoxifylline administration to horses premedicated with frusemide would attenuate the exercise‐induced pulmonary arterial, capillary and venous hypertension to a greater extent than frusemide alone, thereby affecting the occurrence of exercise‐induced pulmonary haemorrhage (EIPH). Using established techniques, we determined right heart and pulmonary vascular pressures in 6 healthy, sound Thoroughbred horses at rest and during exercise performed at maximal heart rate at a workload of 14 m/s on 3.5% uphill grade in the control (no medications), frusemide (250 mg i.v., 4 h pre‐exercise)‐control, and the frusemide (250 mg i.v., 4 h pre‐exercise) + pentoxifylline (8.5 mg/kg bwt i.v., 15 min pre‐exercise) treatments. Sequence of the 3 treatments was randomised forevery horse and 7 days were allowed between them. In the control study, galloping at 14 m/s on 3.5% uphill grade elicited significant right atrial as well as pulmonary arterial, capillary and venous hypertension and all horses experienced EIPH as detected by the presence of fresh blood in the trachea on endoscopic examination. Frusemide administration was not attended by changes in heart rate at rest or during exercise. Although in the frusemide‐control experiments, a significant reduction in mean pulmonary arterial, capillary and wedge pressures was observed both at rest and during galloping at 14 m/s on 3.5% uphill grade, all horses still experienced EIPH. Pentoxifylline administration to standing horses premedicated with frusemide caused nervousness, muscular fasciculations, sweating and tachycardia. Although these symptoms had largely abated within 15 min, there were no significant changes in the right atrial or pulmonary vascular pressures. Exercise in the frusemide + pentoxifylline experiments also caused significant right atrial as well as pulmonary arterial, capillary and venous hypertension, but these data were not found to be significantly different from the frusemide‐control experiments. All horses in the frusemide + pentoxifylline experiments also experienced EIPH. In conclusion, our data indicate that pentoxifylline (8.5 mg/kg bwt i.v., 15 min pre‐exercise) is ineffective in modifying the pulmonary haemodynamic effects of frusemide in exercising horses. It should be noted, however, that we did not examine whether erythrocyte plasticity was altered by the administration of pentoxifylline. Since the intravascular force exerted onto the blood‐gas barrier of exercising horses premedicated with frusemide remained unaffected by pentoxifylline administration, it is concluded that concomitant pentoxifylline administration is unlikely to offer additional benefit to horses experiencing EIPH.