Mitochondrial myopathy in a german shepherd dog

A 9-month-old male German Shepherd dog was referred for evaluation of progressive exercise intolerance. Clinical examination revealed a stiff, stilted gait and marked atrophy and hypotonia of skeletal muscle. The dog had raised creatine kinase (181 U/liter), lactate dehydrogenase (510 U/liter), and aspartate aminotransferase (123.6 U/liter) levels, suggesting a muscle disease. Histochemical evaluation of muscle biopsies revealed the presence of subsarcolemmal oxidative activity, reduced nicotinamide adenine dinucleotide, and succinate dehydrogenase, and the absence of cytochrome oxidase activity. Ragged red fibers were demonstrated with Gomori trichrome stain. Ultrastructural examination of the muscle confirmed the presence of subsarcolemmal accumulations of mitochondria and morphologically atypical mitochondria.     

Semilobar holoprosencephaly in a Morgan horse

A6 1/2‐month‐old Morgan filly was examined because of a history of abnormal behavior, teeth grinding, hypothermia, and electrolyte disturbances when weaned. She was from a breeding farm with several other Morgan horses. The 11‐year‐old dam had been purchased the year before as a proven broodmare, which had several previous foals. Breeding, gestation, and birth of this foal were normal. She was raised with 4 other mares and their offspring on pasture with free access to shelter in an open barn. Supplementary feeding consisted of oats and timothy hay. The owners reported that the foal showed unusual behavior, such as lack of apprehension of people, lack of distress from maternal separation, and a higher activity level than other foals of the same age. The foal extensively chewed the dam's tail and mane, masticated oats slowly with rapid jaw movements without actually swallowing them, and ground her teeth. She frequently nibbled the handler's clothes without biting, ate pebbles, and played with the salt block in the paddock. At 4 1/2 months of age, she was treated for suspected gastroduodenal ulcers and weaned. The referring veterinarian examined her 5 days after weaning because of dull demeanor and excessive teeth grinding. The foal was in thin body condition, hypothermic (37°C, 98.6°F), and tachycardic (60 beats per minute [bpm]) and had decreased borborygmi. Major abnormalities on serum biochemistry were severe hypernatremia (166 mmol/L; reference range 136–144 mmol/L) and hyperchloremia (128 mmol/L; reference range 94–104 mmol/L), azotemia (urea, 11.3 mmol/L; reference range 4.2–8.9 mmol/L), and hyperfibrinogenemia (5.2 g/L, reference range 1.6–2.9 g/L). The only abnormality on the CBC was hemoconcentration (PCV, 0.57 L/L; reference range 0.28–0.44 L/L). The foal was treated with penicillin procaine G^a (20,000 IU/kg [9072 IU/1b] IM q12h) and rifampin^b (5 mg/kg [2.7 mg/1b] PO q8h). The next day the tachycardia worsened (120 bpm) and the foal was estimated to be 5–8% dehydrated. IV fluid therapy with lactated Ringer solution^c (LRS) was initiated, and the antibiotic was changed to ceftiofur^d (2 mg/kg [0.91 mg/1b] IV q12h). The foal and dam were rejoined, and the foal's clinical status improved with resumption of nursing. Serial laboratory testing showed persistent hypernatremia 160 mmol/L) and hyperchloremia (123 mmol/L), azotemia urea 11.3 mmol/L and creatinine 168 umol/L; reference range 80–130 μmol/L), hyperglycemia (8.7 mmol/L; reference range 3.7–6.7 mmol/L), high aspartate aminotranferase activity (662 U/L; reference range 259–595 U/L), and high creatine kinase (CK) activity (1,196 U/L; reference range 108–430 U/L). The foal's condition improved and IV fluids were discontinued. Ceftiofur administration was discontinued and trimethoprim‐sulfamethoxazole^e (25 mg/kg [11.3 mg/1b] PO q12h) was administered for 3 days. During the next month the foal was stable but the abnormal behavior persisted. She was weaned again, and within days marked behavior changes such as circling, throwing the head around compulsively, and severe hind‐end shivering recurred. At examination, the foal was dull, tachycardic (60 bpm), was hypothermic (33.6°C, 92.5°F), had dark red mucous membranes, and was estimated to be 5% dehydrated. Laboratory findings were similar to those of the previous tests except for high fibrinogen (7.1 g/L). The foal was again rejoined with the dam, treated with intramuscular penicillin, and referred     

Inherited myopathy in a young Great Dane

A 3-year-old, male Great Dane was evaluated for an 18-month history of progressive weakness. Histologic evaluation of muscle biopsies revealed distinct cytoarchitectural changes that were indistinguishable from the central "core-like" structures previously described as central core myopathy in this breed. Clinical features of this inherited myopathy are described.     

Inherited myopathy of great Danes

A hereditary, non-inflammatory myopathy occurring in young great Danes with distinctive histological features in muscle biopsy specimens is reviewed. Onset of clinical signs is usually before one year of age and both sexes are affected. Clinical signs are characterised by exercise intolerance, muscle wasting, and an exercise-induced tremor. Although most affected dogs have a severe form of the disease, occasional dogs may have a less pronounced form and survive into adulthood with an acceptable quality of life. Litters containing affected puppies are born to clinically unaffected parents, and an autosomal recessive pattern of inheritance is likely. All recorded cases have had fawn or brindle coat coloration. Elevated serum creatinine kinase concentrations and spontaneous electrical activity in skeletal muscles are frequently found. While originally reported (Targett and others 1994) as a central core myopathy in this breed, the histochemical characteristics of the distinct cytoarchitectural structures differ from those of the well-characterised central core myopathy in human beings. In fact, these structures differ from any known myopathy in human beings and likely represents a unique non-inflammatory myopathy affecting dogs. Until this myopathy is characterised further, the name inherited myopathy in great Danes is suggested.     

Persistent hypoglycemia associated with lipid storage myopathy in a paint foal

A 12‐hours‐old Paint filly was examined because of weakness and dull mentation after birth. Despite IV administered dextrose, the foal remained persistently hypoglycemic with increase in serum activity of muscle and liver enzymes. A postmortem diagnosis of lipid myopathy most similar to multiple acyl‐CoA dehydrogenase deficiency (MADD) was confirmed by findings of myofiber lipid accumulation, elevated urine organic acids, and serum free acylcarnitines with respect to control foals. This report details a case of equine neonatal lipid storage myopathy with many biochemical characteristics of MADD. Lipid storage myopathies should be included as a differential diagnosis in foals with persistent weakness and hypoglycemia.     

Central core myopathy in a great dane

An eight-month-old female great dane was referred for investigation of exercise intolerance that had developed progressively over one month. Examination revealed poor muscle mass, elevated plasma levels of muscle-associated enzymes and electromyographic abnormalities. The dog was euthanased at 15 months old because of severe exercise intolerance. Tissue obtained by biopsy and at post mortem examination revealed prominent well defined central core structures within most muscle fibres, but no other abnormalities. The condition was diagnosed as a central core myopathy.     

Postoperative Myositis in a Neonatal Foal: A Case Report

A foal with azotemia, acidemia, and electrolyte abnormalities was diagnosed with uroperitoneum. The foal was anesthetized with isoflurane, and throughout the 4 hours of anesthesia and abdominal surgery, its mean arterial pressure ranged between 45 and 65 mm Hg. The foal developed a myopathy postoperatively and died 24 hours after surgery.     

Clinical chemistry values and tissue enzyme activities in western barred bandicoots (Perameles bougainville)

BACKGROUND: The western barred bandicoot, Perameles bougainville, is an endangered Australian marsupial species whose survival is threatened by a papillomatosis and carcinomatosis syndrome. Investigations to characterize this syndrome would benefit from species-specific clinical chemistry data. OBJECTIVES: The purpose of this study was to determine plasma biochemical reference values and to determine enzyme activities in various tissues of P. bougainville. METHODS: Heparinized blood samples were collected by jugular venipuncture from 53 clinically healthy bandicoots of both sexes and at 3 geographic locations. Plasma was analyzed for routine clinical chemistry variables using an automated biochemistry analyzer. Tissues obtained following humane euthanasia of 3 bandicoots were analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine kinase (CK), alpha-amylase (AML), and gamma-glutamyltransferase (GGT) activities. RESULTS: Significant differences in the results were found for animals based on geographic location and sex; hence, results were expressed as minimum and maximum values. A population reference interval was calculated for AST activity (20-283 U/L). ALT was found mainly in the liver, with lower levels in cardiac and skeletal muscle and kidneys. AST was detectable in many tissues, including the heart, liver, kidneys, and central nervous system; CK was found in skeletal and cardiac muscle and central nervous system; AML was found in the pancreas; and GGT was found mainly in kidneys with lower levels in the intestines and pancreas. CONCLUSIONS: These findings will facilitate the interpretation of clinical chemistry results from P. bougainville and thereby inform population management and clinical decision-making.     

Hyperalbuminemia associated with hepatocellular carcinoma in a dog

Abstract: A 12‐year‐old, neutered male, mixed‐breed dog was presented to The Ohio State University Veterinary Teaching Hospital with a history of weight loss and weakness. Laboratory abnormalities reported by the referring veterinarian during the past year included increased alkaline phosphatase (ALP) activity, hyperalbuminemia, and nonregenerative anemia. On referral, the dog appeared hydrated and had moderate muscle wasting and hepatomegaly. A large lobular hepatic mass was observed ultrasonographically. Laboratory results included mild to moderate nonregenerative anemia, urine‐specific gravity of 1.035, 3+ proteinuria, increased serum activities of alanine aminotransferase (229 U/L, reference interval 10–55 U/L), ALP (813 U/L, reference interval 15–120 U/L), and the steroid‐induced isoform of ALP (676 U/L, reference interval 0–6 U/L), marked hyperalbuminemia (5.3 g/dL, reference interval 2.9–4.2 g/dL), and an increased A/G ratio (1.7). Hyperalbuminemia was confirmed by reanalysis on 2 different analyzers and by agarose gel electrophoresis, and colloid osmotic pressure (COP) was markedly increased (42.5 mmHg, reference interval 20–25 mmHg). Cytologic examination of a fine‐needle aspirate of the hepatic mass indicated hepatocellular proliferation; histologic examination of an excisional biopsy confirmed hepatocellular carcinoma. Three weeks after surgery, the albumin concentration, A/G ratio, COP, and ALT activity had normalized, but ALP activities remained high. We hypothesized that hyperalbuminemia developed secondary to hepatocellular carcinoma due to increased synthesis of albumin by malignant hepatocytes or due to decreased negative feedback from impaired hepatocellular osmoreceptivity. Hepatocellular carcinoma has been associated with paraneoplastic secretion of other proteins, but hyperalbuminemia has been reported only once in a human patient and has not previously in dogs.     

Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses

In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are associated with the development of laminitis. Although obesity is associated with insulin dysregulation, the mechanism of obesity-associated insulin dysregulation remains to be established. We hypothesized that oxidative stress in skeletal muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty-five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 μIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Markers of oxidative stress (oxidative damage, mitochondrial function, and antioxidant capacity) were evaluated in skeletal muscle biopsies. A Spearman’s rank correlation coefficient was used to determine relationships between markers of oxidative stress and BCS. Furthermore, to assess the role of oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Increasing BCS was associated with an increase in gene expression of a mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related receptor alpha, ERRα) and with increased antioxidant enzyme total superoxide dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared, TotSOD activity was increased and protein carbonyls, a marker of oxidative damage, decreased in the O-HI compared to the L-NI horses. These findings suggest that a protective antioxidant response occurred in the muscle of obese animals and that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia.     

A comparison of foal and adult horse neutrophil function using flow cytometric techniques

Flow cytometric assays were used to compare phagocytic and oxidative burst activity of neutrophils from healthy foals less than 7 days of age with the activity of cells from healthy adult horses. The phagocytosis of Staphylococcus aureus by foal neutrophils was less than that observed for adult neutrophils when autologous serum was used as the source of opsonins in the assay. The use of adult serum did not significantly improve the ability of foal neutrophils to attach bacteria. The oxidative burst activity of foal neutrophils was equivalent to that of adult cells. However, when serum or plasma was incorporated into the oxidative burst assay, foal neutrophils demonstrated greatly reduced autofluorescence and a suppressed response to phorbol myristate acetate (PMA), relative to that demonstrated by adult cells. These results suggest that peripheral blood neutrophils from foals have a reduced ability to phagocytose bacteria relative to that exhibited by adult horse neutrophils and that the oxidative burst activity of foal neutrophils is down-regulated in response to an unidentified serum factor(s). Such changes may contribute to the increased susceptibility of foals to septic disease.     

Effects of dietary supplementation with vitamin E and organic selenium on the oxidative stability of beef.

The effects of supplementation of beef cattle diets with organic Se (0.3 mg/kg) and vitamin E (300 I.U. alpha-tocopheryl acetate/kg feed), for 55 d preceding slaughter, on the antioxidant status and oxidative stability of muscle was examined. Dietary vitamin E supplementation led to an increase (P < 0.05) in plasma, and longissimus muscle alpha-tocopherol levels. In minced longissimus muscle stored in 80% 02:20% CO2, lipid and oxymyoglobin oxidation were lower (P < 0.05) in muscle from vitamin E-supplemented animals compared with unsupplemented animals. Dietary Se supplementation did not significantly affect muscle Se levels, glutathione peroxidase activity, or susceptibility to lipid and oxymyoglobin oxidation in the presence or absence of vitamin E. Covariance analysis indicated that, in addition to muscle alpha-tocopherol, differences in muscle glutathione peroxidase activity, and pH could account for variation in the susceptibility of muscle to lipid and oxymyoglobin oxidation.     

Hypocalcemia in a four-week-old foal

Intake of Rumex, a plant genus of the Polygonaceae family, probably led through the assimilation of oxalic acid, to hypocalcaemia in a four-week old foal. This foal was presented with muscle rigidity and a stiff gait. Both the total and ionized calcium concentrations were low, 1.38 mmol/l and 0.54 mmol/l respectively. The foal was treated with a total of 150 ml of a 20% calcium solution IV. The foals neuromuscular signs resolved within a few hours after receiving calcium solution.     

Gestational Length and First Postpartum Ovulation of Criollo Mares on a Stud Farm in Southern Brazil

The Criollo horse industry requires more efforts toward a better understanding of breed characteristics and physiology; few studies have been conducted in Criollo horses to fulfill this demand. Toward this aim, 70 Criollo mares (between 3 and 28 years of age) underwent physiologic evaluation of the length of gestation, occurrence of foal heat, and interval to postpartum ovulation. Gestation length in the 70 mares was 335.6 ± 10.5 days, varying from 312 to 364 days. The mean (±SD) interval from parturition to first ovulation of 42 mares that foaled between September and December of 2005 and 2006 was 19.9 ± 14.0 days. Eighty-three percent of the mares had an interval to foal heat ovulation shorter than 20 days (35/42). The mean (±SD) parturition to ovulation interval of these mares was 14.2 ± 3.0 days.     

Canine inflammatory myopathies: a clinicopathologic review of 200 cases

A retrospective study was performed on 200 randomly selected cases of inflammatory myopathy in dogs from diagnostic muscle biopsies received at the Comparative Neuromuscular Laboratory, University of California, San Diego. The most common clinical signs in dogs diagnosed with an inflammatory myopathy were generalized weakness, stilted gait, dysphagia, masticatory or generalized muscle atrophy, inability to open the jaw, megaesophagus, and dysphonia. Myalgia was rarely described. Age of onset ranged from 0.25 to 14 years. Genders were equally represented. Breed distribution approximated the 2002 American Kennel Club registration statistics (r = .85) with the notable exception of Boxers and Newfoundlands. From the results of muscle biopsies, clinical signs, and presence or absence of antibodies against type 2M fibers, dogs were classified as a generalized inflammatory myopathy (gIM)--including immune-mediated polymyositis; infectious and preneoplastic myositis; and, rarely, dermatomyositislike or overlap syndromes or unclassified myositis-or a focal inflammatory myopathy (flM)--including masticatory muscle and extraocular myositis. Average creatine kinase (CK) and aspartate aminotransferase (AST) concentrations in gIMs were significantly higher than those with fIMs (P < .05). Neoplasia developed in 12 of 200 dogs within 12 months of diagnosis of polymyositis, with lymphoma diagnosed in 6 of 32 Boxers. Inflammatory myopathy was associated with antibody titers against infectious diseases in 38 dogs. Neospora caninum and Hepatozoon americanum cysts were found in tissues of 2 dogs not serologically tested. Antibodies against an unidentified sarcolemmal antigen were found in 9 of 19 Newfoundlands with polymyositis. The spectrum of canine inflammatory myopathies can be broad, with infectious etiologies relatively common, and can include preneoplastic and uncharacterized syndromes.     

Haematological and biochemical measurements in healthy, adult, free-ranging golden jackals (Canis aureus syriacus) held in captivity

Blood from 31 healthy, free-ranging golden jackals held in captivity for seven days was collected while they were anaesthetised. Haematological and serum biochemical measurements were analysed and the 95 per cent confidence interval for each variable was compared with the reference value for domestic dogs. The measurements of their red blood cells were within the reference interval for dogs, but the jackals had higher white blood cell counts and eosinophil counts than dogs. The male jackals had a higher haematocrit, red blood cell count, mean corpuscular volume and mean corpuscular haemoglobin concentration, and a lower red blood cell distribution width than the female jackals. High activities of muscle enzymes were detected in many of the jackals, in several of which the activity of creatine kinase exceeded 5000 U/l; these were considered abnormal.     

Suspected mitochondrial myopathy in a Jack Russell terrier

A Jack Russell terrier with a history of progressive exercise intolerance was examined at the age of four months and again 10 months later. Clinical examination revealed a stunted, thin dog with a stilted gait. The dog had raised lactate levels before and after feeding and a raised lactate/pyruvate ratio after feeding, indicating a metabolic abnormality. Histochemical evaluation of muscle biopsies revealed subsarcolemmal accumulation of oxidative activity when stained with nicotinamide adenine dinucleotide tetrazolium reductase and ragged red fibres when stained with modified Gomori trichrome; all fibre types were involved. Ultrastructural examination of the muscle confirmed the presence of subsarcolemmal accumulations of mitochondria. Histochemical staining for the activity of enzymes of the Krebs cycle, oxidative phosphorylation and other metabolic cytosolic enzymes failed to demonstrate an abnormality. In view of the clinical picture and the biochemical and histological findings, a tentative diagnosis of mitochondrial myopathy was made. The difficulties associated with diagnosing mitochondrial disorders are discussed.     

Ca2+ ATPase in Dutch warmblood foals compared with Na+, K+ ATPase: intermuscular differences and the effect of exercise

We studied the effects of exercise without or with a subsequent period on pasture on Ca2+ ATPase concentration in foal skeletal muscle, and compared the results with those previously reported on Na+, K+ ATPase. Ca2+ ATPase was measured in homogenates as Ca2+-dependent steady-state phosphorylation from [gamma-32P]ATP. From day 7 after birth, 24 foals were divided into three groups: (i) staying in a box stall (Box); (ii) staying in a box stall with an exercise programme of an increasing number of sprints per day (Exercise); and (iii) staying on pasture (Pasture). Half of the foals (12 with four in each treatment group) were killed after 5 months. The remaining foals stayed on pasture until 11 months. In the 5-month Pasture group, Ca2+ ATPase concentration was 29.4 +/- 4.3 nmol/g wet weight (wt) (n = 4) in gluteus medius muscle, 25.2 +/- 3.3 nmol/g wet wt (n = 4) in semitendinosus muscle (both mixed fibre type), and 4.1 +/- 1.7 nmol/g wet wt (n = 3) in the slow masseter muscle. These values were not altered by exercise or by box rest. This was in contrast to the Na+, K+ ATPase concentration which was not different between the three muscles, but showed a 20% rise in gluteus medius and semitendinosus muscle after exercise. In the period from 5 to 11 months on pasture, there was no change in Ca2+ ATPase in any group. In conclusion, the Ca2+ ATPase concentration in foal muscle is around 6-fold higher in mixed fibres than in slow fibres. Furthermore, the enzyme is not up- or down-regulated by sprint exercise or subsequent rest.