Morphological alterations in oxidative muscles and mitochondrial structure associated with equine atypical myopathy

in Equine Veterinary Journal (2007), 39(1), 26-32

REASONS FOR PERFORMING STUDY: There is a lack of well documented studies about muscular lesions in equine atypical myopathy (EAM). OBJECTIVES: To characterise morphopathological changes of striated ... [more ▼]

REASONS FOR PERFORMING STUDY: There is a lack of well documented studies about muscular lesions in equine atypical myopathy (EAM). OBJECTIVES: To characterise morphopathological changes of striated muscles and myocardium, to progress understanding of this disease. METHODS: Thirty-two horses age 0.5-7 years kept on pasture were referred for a sudden ataxia/myoglobinuria syndrome. Clinical examination (stiffness, muscle pain, muscle fasciculations, abnormal gait, recumbency, myoglobinuria, tachycardia, sweating) and plasma CPK, LDH and AST levels were consistent with extensive myonecrosis and, together with anamnestic data, with so-called 'equine atypical myopathy' (EAM), a disease of unknown aetiology reported since 1939. Macroscopic and microscopic (histology, histoenzymology, ultrastructure) lesions were evaluated. RESULTS: Necropsic examination revealed large areas of muscle necrosis, the extent and severity of which varied between cases and muscles, but which were clearly more constant and severe in respiratory and postural muscles and in the myocardium. Histology highlighted a multifocal and monophasic process compatible with Zenker degeneration/necrosis that mostly and segmentally affected type 1 fibres. Histochemical evaluation revealed a weak and disorganised pattern of NADH tetrazolium reductase staining, the absence of calcium salts precipitates and a dramatic accumulation of lipid droplets. Ultrastructural examination often revealed fibres of which the sole modifications were altered mitochondria and sarcoplasmic lipidosis. CONCLUSIONS: Taken together, the data suggest that a primary alteration of mitochondria should be considered, although secondary mitochondrial abnormalities have yet to be ruled out. POTENTIAL RELEVANCE: The morphological features gathered here reveal that EAM shares most of the characteristics of toxic myopathies. [less ▲]

Pharmacologie clinique des bisphosphonates : revue de littérature axée sur le tiludronate chez le cheval.

in Annales de Médecine Vétérinaire (2007), 151

Comparative pharmacokinetics of two dosage rates of tiludronate in healthy adult horses

Poster (2007)

Change in blood antioxidant status of horses moved from a stable following diagnosis of equine motor neuron disease

in Canadian Veterinary Journal = Revue Vétérinaire Canadienne (2007), 48(11), 1165-1167

The antioxidant status of 10 horses living in stable 1 where 2 cases of equine motor neuron disease had previously been diagnosed was assessed before and 9 weeks after moving to another stable. Duration ... [more ▼]

The antioxidant status of 10 horses living in stable 1 where 2 cases of equine motor neuron disease had previously been diagnosed was assessed before and 9 weeks after moving to another stable. Duration of residence in stable 1, subsequent moving, or both, significantly affected several parameters of the antioxidant status. [less ▲]

Tetanus in the horse: a review of 31 cases

in Proceedings of the 45th Annual Congress of the British Equine Veterinary Association (2006, September 14)

Assessment of a bone biopsy technique for tiludronic acid dosage in horses: a preliminary study

Poster (2006, September)

Introduction Tiludronic acid as a bisphosphonate has a strong affinity for bone, making difficult the assessment of its PK profile in this deep compartment on living animals. The invasive nature of sample ... [more ▼]

Introduction Tiludronic acid as a bisphosphonate has a strong affinity for bone, making difficult the assessment of its PK profile in this deep compartment on living animals. The invasive nature of sample collection remains a limiting factor. This study was carried out in order to assess a bone biopsy technique allowing the repetition of sampling over a long period of time to dose tiludronic acid in equine bone. Material and Methods Six healthy 4- to 8-year-old Standardbred geldings were treated with tiludronic acid 1 mg/kg in a saline infusion over 30 minutes. The horses were subjected to euthanasia on days 1, 43, 57, 92, 182 and 222 post-treatment, respectively. Bone samples (test samples and larger reference samples) were taken at 4 sites per side and per horse: the lateral aspect of the metacarpal bone III (MCIII) of the forelimb, the 13th rib, the tuber coxae and the cuboïd bone. Test samples were taken with a 5-mm diameter dental drill (Implanteo™, Anthogyr), while larger reference samples were taken around the drill sample sites with an osteotome. All samples were taken immediately after euthanasia. Tiludronic acid concentrations were measured by HPLC with UV detection. Results The tuber coxae was the easiest site to sample. The sample site of the MCIII was easily accessible but due to the extreme hardness of the bone, the drill sampling was technically difficult to perform. Drill samples obtained from the 13th rib were very small, and the access more limited. Finally, the access to the cuboïd bone required considerable dissection, not performable in vivo. Extraction and dosage of tiludronic acid from the MCIII was difficult for technical reasons in most cases, in drill samples as well as in reference samples, and most (96%) of the values obtained were considered unreliable. This was also true for some samples from the 13th rib and from the cuboïd bone, to a lesser extent (42% of unreliable values for both sites). Moreover, for these two sample sites, less technical problems were encountered for the extraction and dosage of tiludronic acid in drill samples than in reference samples. No extraction or dosage problem was encountered with the tuber coxae samples. The ratio of tiludronic acid concentrations in drill versus reference samples ranged from 73% to 185% (mean: 124%), 65% to 208% (mean: 118%), and 26% to 110% (mean: 62%) respectively in the tuber coxae, 13th rib and cuboïd bone. In all but one horse, the highest concentrations in tiludronic acid were found in the tuber coxae, while the lowest values tended to be in the cuboïd bone at any time post-treatment. Tiludronic acid was still found in all bone samples 7 months after treatment. Discussion As previously reported with other tools, the drill tested in this study should permit to conveniently perform bone biopsies in the equine tuber coxae. This biopsy site would be the most appropriate for repeated sampling to dose tiludronic acid over time. This would help to design appropriate PK/PD studies with tiludronic acid in horses. This study also further confirms the long persistence of tiludronic acid in equine bone. [less ▲]

Morphological alterations in oxidative muscles and mitochondrial structure associated with equine atypical myopathy

in Equine Veterinary Journal (2006), 39(1), 26-32

Reasons for performing study: There is a lack of well documented studies about muscular lesions in Equine Atypical Myopathy (EAM). Objectives: To characterize morphopathological changes of striated ... [more ▼]

Reasons for performing study: There is a lack of well documented studies about muscular lesions in Equine Atypical Myopathy (EAM). Objectives: To characterize morphopathological changes of striated muscles and myocardium, with the aim to progress in the understanding of this disease. Methods: Thirty-two 0.5- to 7-year-old horses kept on pasture were referred for a sudden ataxia/myoglobinuria syndrome. Clinical examination (stiffness, muscle pain, muscle fasciculations, abnormal gait, recumbency, myoglobinuria, tachycardia, sweating) and plasma CPK, LDH and AST levels were consistent with extensive myonecrosis and, together with anamnestic data, with so-called “Equine Atypical Myopathy” (EAM), a disease of unknown etiology repeatedly reported in the literature since 1939. Macroscopic and microscopic (histology, histoenzymology, ultrastructure) lesions were evaluated. Results: Necropsic examination revealed large areas of muscle necrosis, the extent and severity of which varied between cases and muscles, but which were clearly more constant and severe in respiratory and postural muscles and in the myocardium. Histology highlighted a multifocal and monophasic process compatible with Zenker degeneration/necrosis that mostly and segmentally affected type-1 fibres. Histochemical evaluation revealed a weak and disorganized pattern of NADH tetrazolium reductase staining, the absence of calcium salts precipitates and a dramatic accumulation of lipid droplets. Ultrastructural examination often revealed fibres of which the sole modifications were altered mitochondria and sarcoplasmic lipidosis. Conclusions: Taken together, the data suggest that a primary alteration of mitochondria should be considered, although secondary mitochondrial abnormalities have yet to be ruled out. Potential relevance: The morphologic features gathered here reveal that EAM shares most of the characteristics of toxic myopathies. [less ▲]

Equine Motor Neuron Disease in Belgium: a retrospective study

Poster (2006)

A case of Rhodococcus equi infection in an adult probably immuno-compromised horses

in Proceedings of the Leipziger Tierärzte Kongress (2005)

Evaluation of the pharmacological effects of the bisphosphonate tiludronate in the horse at exercise after a long term immobilisation period

Report (2005)