White muscle disease in foals: focus on selenium soil content. A case series.

BACKGROUND: White muscle disease (WMD) is a nutritional myopathy caused by selenium (Se) deficiency. In most soils, Se is present in low concentrations, sometimes even below 0.2 mg/kg, a trend which is seen in many countries. Apart from total soil Se concentrations, soil conditions may be such that the bio-availability of Se is so low that it causes very low uptake in plants which can ultimately lead to deficiency problems in animals. This is the first case series to report clinical WMD in foals in areas deficient in Se, in the Netherlands. The aim of the current report is to provide an overview of the clinical history, symptoms and (clinical) pathology of 8 newborn foals living at 4 different premises and suffering from WMD together with the effectiveness of Se and vitamin E (Vit E) supplementation in the affected foals, their dams and herd members. Hands on practical information is provided to apply a correct and effective Se supplementation management in horses and which pitfalls need to be avoided for a successful approach. CASE PRESENTATION: Case features and history were mapped out for all foals. Se and Vit E status were assessed for the foals, their dams and herd members, at admission and after 3 months of Vit E/Se supplementation. Common symptoms were muscle weakness, inability to rise, lethargy and inadequate suckle reflex together with increased serum muscle enzymes and low glutathione peroxidase (GSH-Px) and low to normal serum vit E levels. Necropsy revealed necrosis of skeletal muscles consistent with nutritional myopathy. Se status of the dams and herd members correlated well with the Se status of the foals. All surviving foals (n = 6) showed normal Vit E and GSH-Px levels after supplementation, likewise, all horses tested at premises 1, 3 and 4. However, dams and herd members in premises 2 showed no normalization. Horses of that premises were diagnosed with pyrrolizidine intoxication one year prior to the study. CONCLUSIONS: Certain regions in the Netherlands are sufficiently Se deficient to predispose newborn foals to develop WMD, especially when they are being fed a diet that mainly consists of locally harvested roughage.

CONGENITAL NUTRITIONAL MYODEGENERATION (WHITE MUSCLE DISEASE) IN A GIRAFFE ( GIRAFFA CAMELOPARDALIS) CALF.

It is well known that vitamin E and selenium deficiencies in domestic ruminants can lead to white muscle disease. After a clinically normal gestation period at Ouwehand Zoo in the Netherlands, a newborn giraffe ( Giraffa camelopardalis) calf showed clinical signs of white muscle disease almost immediately after birth. The calf was rejected by the mother and was euthanized 3 days later because of deterioration of clinical signs. At necropsy, pulmonary edema and pallor of skeletal and heart muscles was noted. Histologically, there was hyaline degeneration of skeletal muscle myocytes and pulmonary edema. Blood concentrations of vitamin E were ≤ 0.7 mg/L. Based on clinical, biochemical, and gross and microscopic pathological findings, congenital nutritional myodegeneration was diagnosed. This case of neonatal white muscle disease is particularly remarkable given that the diet of the dam contained more than the recommended amount of vitamin E.

Mechanisms of white matter damage in multiple sclerosis.

Glia cells are mediators as well as targets of the chronic inflammatory process in the central nervous system of multiple sclerosis (MS) patients. They are involved in the control of autoimmunity, in the propagation and termination of the inflammatory reaction, in the induction of demyelination and neurodegeneration, and in remyelination and scaring. Demyelination, as well as neuronal and GLIA cell damage are induced by different immunological mechanisms including components of the adaptive and innate immune system. Oxidative injury resulting in mitochondrial dysfunction is one important mechanism of tissue injury. It is in part driven by the inflammatory response and the production of oxygen radicals mainly in microglia and macrophages. With increasing age of the patients and disease progression, oxidative injury is further amplified by additional mechanisms including central nervous system damage related microglia activation, progressive mitochondrial damage, and age-dependent iron accumulation within the human central nervous system. The inflammatory mechanisms associated with lesion formation in MS are to a large extent reflected in experimental models of inflammatory demyelination, such as autoimmune encephalomyelitis. This is not the case for the amplification mechanisms of oxidative injury, which mainly operate in the progressive stage of the disease.

The influence of selenium deficiency on chosen biochemical parameters and histopathological changes in muscles of goat kids.

The research was conducted on 40 young alpine goats (kids) divided into two groups. First group consisted of 20 kids demonstrating clinical signs of muscular dystrophy. Second group was a control and consisted of 20 animals that received intramuscular injection (2ml per animal) of vitamin E and selenium preparation containing in 1ml 50 mg of tocopherol acetate, 0.5mg of sodium selenite and solvent on 2nd day of life. The kids were clinically examined and blood for laboratory analyses was sampled three times from day 5 of their life in 10 day intervals. In addition, six 24 days old kids demonstrating clinical signs of muscular dystrophy and six control kids were subjected to biceps femoris biopsy. Serum total protein, glucose, triglycerides, cholesterol as well as AST, CK and LDH were determined in all the animals. In addition, the activity of glutathione peroxidase (GSH-Px) was determined in whole blood and serum concentrations of selenium and vitamin E were deter-mined in 6 kids from each group. Total lactate dehydrogenase activity and its separation into isoenzymatic fractions were determined in the collected biopsy material. The muscle samples collected were additionally subjected to histopathological examination consisting of HE staining and HBFP staining to detect necrotic muscle fibers. Symptoms of muscular dystrophy began to appear in the first group between 17 and 23 days of age and included tremors of the limbs, poor posture, stilt gait and increased time of laying. The control animals did not show any symptoms of the disease during the experiment. Hypo-proteinemia, hypoglycemia, cholesterol reduction and elevated triglycerides level associated with lipolysis of adipose tissue have been found in the sick kids. A significant decrease in selenium, vitamin E and activity of glutathione peroxidase levels was observed in the kids with symptoms of muscular dystrophy. The activity of AST, CK and LDH was significantly higher in the animals with symptoms of the disease as well. Five isoenzymes were obtained in the electrophoretic separation of lactate dehydrogenase into isoenzymatic fractions in the muscle tissue. LDH4and LDH5 isoenzymes were dominating, and a significant increase in LDH5 fraction of the sick animals was also observed. Histopathological examination of muscle samples from sick animals revealed changes characteristic for the presence of Zenker necrosis.

Cerebrovascular reactivity as a determinant of deep white matter hyperintensities in migraine.

OBJECTIVE: To evaluate the association between the cerebrovascular reactivity to carbon dioxide (CO2-CVR) and the deep white matter hyperintensity (WMH) burden in patients with migraine. METHODS: A total of 86 nonelderly patients with episodic migraine without vascular risk factors and 35 headache-free controls underwent 3T MRI. Deep WMHs were quantified with a segmentation method developed for nonelderly migraineurs. The interictal CO2-CVR was measured with transcranial Doppler with the breath-holding method. The mean breath-holding index of the bilateral middle cerebral arteries (MCA-BHI) was square root transformed and analyzed with univariate and multivariate logistic regression models to determine its association with the highest tertiles of deep WMH burden (number and volume). RESULTS: A low MCA-BHI was independently associated with the highest tertile of deep WMH number in patients with migraine (adjusted odds ratio [OR] 0.02, 95% confidence interval [CI] 0.0007-0.63, p = 0.026). In controls, the MCA-BHI was not associated with deep WMH number. Interaction analysis revealed that migraine modified the effect of MCA-BHI on deep WMH number (p for interaction = 0.029). The MCA-BHI was not associated with increased deep WMH volume in both patients and controls. Age was independently associated with deep WMH volume in patients (adjusted OR 1.07, 95% CI 1.004-1.15, p = 0.037). CONCLUSIONS: In this study, we found a migraine-specific association between a reduced CVR to apnea and increased number of deep WMHs in healthy, nonelderly patients with migraine. A dysfunctional vascular response to apnea may predispose migraineurs to an increased risk of WMHs.

Rationale for clinical trials of selenium as an antioxidant for the treatment of the cardiomyopathy of Friedreich's ataxia.

A pure selenium deficiency is harmful to the heart and causes a fatal dilated congestive cardiomyopathy in animals (white muscle disease) and in man (Keshan disease). Both of these syndromes are selenium-responsive. A deficiency of the micronutrient has also been reported in patients with Friedreich's ataxia and there are histological similarities between Friedreich's cardiomyopathy and Keshan disease. A low selenium status results in reduced selenium-dependent glutathione peroxidase activity. This essential antioxidant enzyme protects membrances from oxidative deterioration, a function it shares in common with vitamin E. As iron-induced mitochondrial lipid peroxidation is central to the pathology of Friedreich's ataxia, the administration of selenium supplements should normalize the antioxidant activity of myocardial glutathione peroxidase and slow the progression of the life-shortening cardiomyopathy associated with this illness.

The two faces of selenium-deficiency and toxicity--are similar in animals and man.

The purpose of this review article is to demonstrate the close parallelism of daily requirements, biological activity and minimum and maximum tolerable levels of selenium for animals and man. In addition, the carcinogenic/anticarcinogenic properties of selenium are discussed and a postulate of how these dichotomous effects may occur in accordance with selenium-induced immunomodulation is presented. A review of pertinent literature pertaining to the biological action of selenium in animals and man, including deficiency, toxicity, carcinogenicity and effects on immunity, is included to support these concepts. The predominant biochemical action of selenium in both animals and man is to serve as an antioxidant via the selenium-dependent enzyme, glutathione peroxidase, and thus protect cellular membranes and organelles from peroxidative damage. The signs and symptoms of selenium deficiency closely simulate each other for animals and man. Severe deficiency is characterized by cardiomyopathy while moderate deficiency results in less severe, myodegenerative syndromes such as muscular weakness and pain as well as a variety of other selenium-associated diseases. Clinical manifestations of many of these disorders require contributory factors, such as stress, to precipitate symptoms which are documented for animals and implicated for humans. Current evidence suggests that a daily selenium consumption for man of approximately 30 micrograms is necessary to prevent the selenium-deficient syndrome, Keshan disease, while approximately 90 micrograms/day/adult should be the minimum daily requirement for optimum biological performance. Recognizing that humans in several countries do not meet the proposed minimum daily requirement of 90 micrograms, several compelling reasons are presented in deriving this minimal daily nutritional intake. Selenosis can occur in laboratory animals, livestock, and humans following long-term exposure to selenium concentrations as low as 5 mg selenium/kg of diet (5 ppm). The selenium-induced lesions for all species are similar, which once again illustrates a positive corollary for selenium effects in both animals and man. From compilation of available data, the maximum tolerable level for selenium in man could be considered in the range of 1000 to 1500 micrograms/day. This is in contrast to the currently recommended maximum human tolerable level of 500 micrograms/day. The amount of selenium that can be tolerated, however, is dependent upon individual biological variation, nutritional status and general state of health.(ABSTRACT TRUNCATED AT 400 WORDS)

An outbreak of white muscle disease in lambs born of ewes on a zero grazing system in Natal.

White muscle disease appeared in lambs born of ewes in the zero grazing group during the course of a comparative fertility trial on ewes on various systems of husbandry. Analysis of the feed showed barely adequate selenium in the maize silage and a deficiency in the soil on which the high lysine maize was grown. Treatment of the lambs with a selenium/vitamin E injection rapidly controlled the condition. This deficiency may be more widespread than is presently realised.

[Congenital white muscle disease in a Belgian blue calf]. / Congenitale white muscle disease bij een Belgisch witblauw kalf.

In this case report about white muscle disease (WMD) in a Belgian Blue herd, the disease is described both as an individual and as a herd problem. Aetiology, diagnosis, and therapy of WMD are discussed. WMD is a disease of animals with muscle damage due to the presence of free radicals. Unsaturated fatty acids in the cell membrane are transformed into a radical form in a chain reaction: a fatty acid next to the fatty acid radical can be transformed into another free radical. In healthy animal the chain reaction is stopped by anti-oxidants such as vitamin E and glutathione peroxidase. WMD can occur when more free radicals are produced than the available anti-oxidants can deal with. The disease occurs in calves, lambs, and foals.

Deep hypothermic circulatory arrest during the arterial switch operation is associated with reduction in cerebral oxygen extraction but no increase in white matter injury.

OBJECTIVE: Deep hypothermic circulatory arrest may be associated with increased neural injury. We investigated whether short periods of deep hypothermic circulatory arrest are associated with altered neurophysiologic recovery or greater risk of injury. METHODS: Eighteen term infants with transposition of the great arteries undergoing the arterial switch operation were enrolled. Deep hypothermic circulatory arrest was used in 11, and bypass alone in 7. Near-infrared spectroscopy and amplitude-integrated electroencephalography were recorded with standard monitoring during and from 4 to 16 h after surgery. Fractional tissue oxygen extraction was determined from arterial oxygen saturation and venous weighted intracerebral oxygenation. Magnetic resonance imaging was performed before and 5 to 7 days after surgery. RESULTS: There were no significant differences between patients requiring deep hypothermic circulatory arrest (median, 5 min; range, 3-6 min) or cardiopulmonary bypass only at the beginning of surgery. At the end of surgery, amplitude-integrated electroencephalography minimum amplitude was significantly lower in the deep hypothermic circulatory arrest group (P < .05), and fractional tissue oxygen extraction tended to be lower (P = .068). After surgery, deep hypothermic circulatory arrest was associated with significantly higher tissue oxygenation index, lower fractional tissue oxygen extraction, and lower core temperature (P < .05). Magnetic resonance imaging-defined white matter injuries before and after surgery were similar between groups. CONCLUSIONS: In this prospective, observational study, brief deep hypothermic circulatory arrest during arterial switch was associated with reduced cerebral oxygen uptake during recovery, with transient electroencephalographic suppression but no increase in risk of white matter injury.

Studies on serum tocopherol and selenium levels and blood glutathione peroxidase activities in lambs with white muscle disease.

For the investigation of the cause of white muscle disease (WMD), tocopherol (Toc) and selenium (Se) levels and blood glutathione peroxidase (GSH-Px) activities were examined using lambs with WMD and their ewes. Serum Se levels of 4 lambs with WMD were low under 30 ppb, lambs showing very low levels below 15 ppb. The serum Se level was correlated with blood GSH-Px activity showing remarkably low activities in the lambs with WMD. Se contents in the organs of lambs with WMD were lower than those of control lambs, and particularly liver Se contents were deficient levels below 50 ppb. Serum Toc levels were normal, but alpha-Toc contents in organs showed very low levels, especially in the liver. The serum Toc and Se levels and blood GSH-Px activities of their ewes and other sheep kept in the same farm revealed similar results to those of lambs with WMD. Feedstuffs supplied on the farm showed the deficient level of the Se content below 50 ppb and a very low level of alpha-Toc. It was concluded that WMD of lambs in Hokkaido was nutritional muscular dystrophy resulted from deficiencies of Toc and Se to their ewes.

Effects of selenium and vitamin E on blood selenium levels, tissue glutathione peroxidase activities and white muscle disease in sheep fed purified or hay diets.

The effects of selenium and vitamin E on blood selenium levels and tissue glutathione peroxidase activities were determined in sheep fed purified and hay diets. A significant increase of blood levels of this element and tissue glutathione peroxidase activities was found in sheep given selenium as compared to those not receiving this element. Of the tissues examined, the highest glutathione peroxidase activity was found in the heart. Vitamin E had no influence on either the blood selenium levels or upon the tissue glutathione peroxidase activity. With hydrogen peroxide as the substrate, tissue glutathione peroxidase activity was not correlated with the incidence of white muscle disease. Evidence is presented to suggest that 0.1 ppm dietary selenium is not sufficient under some conditions to meet the physiological requirements for this element.

White muscle disease of foals.

White muscle disease (nutritional myodegeneration) of foals is a peracute to subacute myodegenerative disease affecting skeletal and cardiac muscle. It is caused by a dietary deficiency of selenium and vitamin E, usually in association with predisposing factors such as a high intake of dietary unsaturated fats or unaccustomed exercise. White muscle disease has been observed in foals from birth to 1 year of age, particularly those foals born to dams fed selenium-deficient diets, during gestation. The disease in foals may present as an acute, fulminant syndrome, which is rapidly fatal, or a subacute syndrome characterized by profound muscular weakness. Failure of passive transfer, aspiration pneumonia, and stunting are frequent complications. Markedly increased muscle enzyme and low glutathione peroxidase activities are common findings in affected foals. Foals with the subacute form of the disease may survive if they are supplemented early with selenium; however, mortality rates ranging from 30% to 45% have been reported, even for this form of the disease.

Studies on serum tocopherol, selenium levels and blood glutathione peroxidase activities in calves with white muscle disease.

For the purpose of clarifying the cause of white muscle disease (WMD) in calves, tocopherol and selenium levels and blood glutathione peroxidase (GSH-Px) activity were measured on 10 calves with WMD and nine of their dams. The main clinical symptoms of the 10 calves with WMD were motor disturbances including recumbency and stiffness. Serum enzyme activities (GOT, GPT, CPK, LDH) in calves with WMD increased markedly, and this increase was also observed in some of their dams. Serum tocopherol levels of calves with WMD were low, 70% of which showing deficient levels of less than 70 micrograms/100 ml. Serum selenium levels of all the calves were lower than 35 ppb, indicating a deficiency, and were accompanied by low blood GSH-Px activity. alpha-Tocopherol and selenium concentrations in organs were very low. Dams of calves with WMD showed low serum tocopherol levels, 22% of which indicating deficient levels below 150 micrograms/100 ml. Serum selenium levels in dams showed a marked decrease to under 20 ppb, and also low blood GSH-Px activity. Feedstuffs supplied in the farms to affected calves indicated very low alpha-tocopherol contents (below 3 mg/100g DM) and low selenium concentrations below 50 ppb in DM. It was concluded that WMD in calves was attributable to nutritional muscular dystrophy caused by deficiencies in tocopherol and selenium in feedstuffs supplied to their dams.

Effects of selenium and vitamin E deficiencies on reproduction, growth, blood components, and tissue lesions in sheep fed purified diets.

Three 2 X 2 factorial experiments were conducted with sheep fed purified diets to determine the effects of selenium and vitamin E on the incidence of white muscle disease (WMD) and blood components. All lambs reaching 6 weeks of age in the group receiving no vitamin E or selenium developed WMD lesions, whereas only a few lambs in either the +E - Se or -E + Se treatment groups developed these lesions. Plasma activities of creatine phosphokinase, lactic dehydrogenase and glutamic oxaloacetic transaminase were significantly elevated in lambs receiving no vitamin E or selenium, whereas these enzyme activities in those receiving only selenium were non-significantly elevated. The enzyme activities in plasma of those on the +E - Se or +E + Se treatments were maintained at low levels, suggesting vitamin E alone is more effective in preventing WMD than selenium alone. The metabolic interactions of these essentials are discussed.