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.

Detection of Se, Vit. E, Vit. A, MDA, 8-OHdG, and CoQ10 Levels and Histopathological Changes in Heart Tissue in Sheep with White Muscle Disease.

This study was carried out to determine vit. E, Se, vit. A, malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and ubiquinone-10 (CoQ10) levels and histopathological changes in sheep with white muscle disease (WMD). A total of 30 sheep were used; 20 sheep with WMD were brought to our clinic for diagnosis and treatment at various times, and 10 healthy sheep were in the control group. The Se, vit. E, vit. A, MDA, 8-OHdG, and CoQ10 values of the healthy and WMD sheep were as follows: 0.917 ± 0.037, 0.790 ± 0.067; 1.190 ± 0.011, 1.090 ± 0.021; 5.400 ± 0.275, 5.200 ± 0.173; 1.602 ± 0.264, 2.636 ± 0.576; 0.656 ± 0.197, 1.485 ± 0.271; and 0.280 ± 0.044, 1.753 ± 0.551 respectively (p < 0.05). According to histopathological and immunohistochemical findings in the WMD group, hyaline degeneration, Zenker's necrosis, and dystrophic calcification were observed in the muscle fibers. Immunohistochemically, 8-OHdG staining of the heart tissue determined a severe 8-OHdG expression in the WMD group. The findings of this study suggest that MDA, 8-OHdG, and CoQ10 values could be used as diagnostic and prognostic biomarkers in sheep affected with WMD.

Development and clinical consequences of white matter lesions in Fabry disease: a systematic review.

BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disorder that might result in, amongst other complications, early stroke and white matter lesions (WMLs). More insight in WMLs in FD could clarify the role of WMLs in the disease presentation and prognosis in FD. In this systematic review we assessed the prevalence, severity, location and course of WMLs in FD. We also systematically reviewed the evidence on the relation between WMLs, disease characteristics and clinical parameters. METHODS: We searched Pubmed, EMBASE and CINAHL (inception to Feb 2018) and identified articles reporting on FD and WMLs assessed with MRI. Prevalence and severity were assessed for all patients combined and divided by sex. RESULTS: Out of 904 studies a total of 46 studies were included in the analyses. WMLs were present in 46% of patients with FD (581 out of 1276 patients, corrected mean age: 38.8 years, range 11.8-79.3) and increased with age. A total of 16.4% of patients (31 out of 189 patients, corrected mean age: 41.1 years, range 35.8-43.3 years) showed substantial confluent WMLs. Men and women showed comparable prevalence and severity of WMLs. However, men were significantly younger at time of WML assessment. Patients with classical FD had a higher chance on WMLs compared to non-classical patients. Progression of WMLs was seen in 24.6% of patients (49 out of 199 patients) during 38.1 months follow-up. Progression was seen in both men and women, with and without enzyme replacement therapy, but at an earlier age in men. Stroke seemed to be related to WMLs, but cerebrovascular risk factors, cardiac and renal (dys)function did not. Pathology in the brain in FD seemed to extend beyond the WMLs into the normal appearing white matter. CONCLUSIONS: A significant group of FD patients has substantial WMLs and male patients develop WMLs earlier compared to female patients. WMLs could be used in clinical trials to evaluate possible treatment effects on the brain. Future studies should focus on longitudinal follow-up using modern imaging techniques, focusing on the clinical consequences of WMLs. In addition, ischemic and non-ischemic pathways resulting in WML development should be studied.

Apcdd1 stimulates oligodendrocyte differentiation after white matter injury.

Wnt signaling plays an essential role in developmental and regenerative myelination of the CNS, therefore it is critical to understand how the factors associated with the various regulatory layers of this complex pathway contribute to these processes. Recently, Apcdd1 was identified as a negative regulator of proximal Wnt signaling, however its role in oligodendrocyte (OL) differentiation and reymelination in the CNS remain undefined. Analysis of Apcdd1 expression revealed dynamic expression during OL development, where its expression is upregulated during differentiation. Functional studies using ex vivo and in vitro OL systems revealed that Apcdd1 promotes OL differentiation, suppresses Wnt signaling, and associates with ß-catenin. Application of these findings to white matter injury (WMI) models revealed that Apcdd1 similarly promotes OL differentiation after gliotoxic injury in vivo and acute hypoxia ex vivo. Examination of Apcdd1 expression in white matter lesions from neonatal WMI and adult multiple sclerosis revealed its expression in subsets of oligodendrocyte (OL) precursors. These studies describe, for the first time, the role of Apcdd1 in OLs after WMI and reveal that negative regulators of the proximal Wnt pathway can influence regenerative myelination, suggesting a new therapeutic strategy for modulating Wnt signaling and stimulating repair after WMI.

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.

Congenital nutritional myodegeneration (white muscle disease) in a red deer (Cervus elaphus) calf.

CASE HISTORY: A 5-day-old red deer calf was submitted with tachypnoea and dyspnoea, and was reluctant to move. CLINICAL FINDINGS: Muscular damage was established via elevated creatinine phosphokinase (CPK) activities (5,000 U/L), while concentrations of Se in whole blood were low (24.8 nmol/L). The animal died despite treatment with penicillin and streptomycin and 0.1 mg/kg Se/vitamin E administered by S/C injection. DIAGNOSIS: Necropsy and histological examination of cardiac and skeletal muscle confirmed the presumptive diagnosis of congenital white muscle disease (WMD). Prophylactic administration of a Se/vitamin E commercial preparation (as above) to another calf born in the same herd one month later was associated with good health and apparently normal growth and development. CLINICAL RELEVANCE: Congenital WMD due to Se deficiency can be fatal in red deer calves. However, prophylactic administration of Se and vitamin E to neonatal calves may be beneficial for neonatal red deer calves.

A possible case of white muscle disease complicated by arthrogryposis and atresia ani in and Anglo Nubian kid in Trinidad and Tobago

There have been many instances of livestock congenital defects in Trinidad and Tobago; however, this case is an interesting one because of the number of defects observed and systems involved in an individual animal. A 2-day-old male Anglo Nubian kid was presented to The University of the West Indies, Faculty of Medical Sciences, School of Veterinary Medicine. The kid was weak, unable to walk, unable to stand and had not suckled since birth, unlike its twin. After detailed physical examination the kid was euthanized and subsequent post mortem examination and histological analysis of tissues revealed atresia ani, numerous muscular defects, severe hepatic necrosis and ankylosis of the joints, strongly suggesting a possible complicated case of White Muscle Disease.

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.

[Electron microscopic studies in enzootic muscular dystrophy in cattle]. / Elektronenmikroskopische Untersuchungen bei der enzootischen Muskeldystrophie des Rindes.

Electron microscopy was used to examine the sekeletal muscles of young cattle, aged between 13 and 24 months, with spontaneous enzootic myodystrophy (nutritional myodegeneration due to selenium deficiency, white muscle disease). The animals had been received from Sumava District, Southern Bohemia, an area known for shortage of selenium. Outbreaks of clinical illness were recorded from them between four and 18 days from the beginning of grazing. Most of the ultrastructural changes included decomposition of myofibrils and hyalinisation of fibres as well as defective fibril synthesis (Z-striation abnormality), some of the latter phenomena recordable even from regenerating fibre. However, minor disorders only were established from the mitochondria, sarcoplasmic reticulum, components of sarcoplasm, and vessels. There were far-reaching ultrastructural similarities to nutritional myodegeneration of sheep. The changes recorded are likely to suggest a specific role played by selenium in the formation and preservation of myofibril proteins.

Cardiac myopathies in neonatal lambs: histological and histochemical studies.

White muscle disease (WMD), a selenium-responsive cardiac myopathy in neonatal lambs has been described from southern Iran. 15 lambs in terminal condition were referred to our lab. All the lambs were observed with the affected hearts. The lambs examined were between the postnatal ages of 1 week and 3 months. Gross changes included chalky-white appearance of entire endocardium of right ventricle and subendocardial plaques in the interventricular septum and left ventricular wall. Histologically the affected myofibrils showed swelling, acidophilia, fragmentation, segmental and patchy myonecrosis, round muscle cell nuclei, loss of sarcoplasm and sarcolemmal collapse. Purkinje fibers were relatively unaffected. Histochemical studies including Von Kossa and other stains indicated marked deposition of calcium salts in the cytoplasm of the damaged myofibrils. Calcium salts appeared as uniform, fine granules in relation to individual fiber striations. It appears that rapid accumulation of calcium into the damaged cells possibly interferes with the mitochondrial activity. As mitochondria bind excessive calcium, their capacity to respire and phosphorylate is depressed thus causing myocardial necrosis. The cardiac myopathy noted in our investigation is probably due to selenium deficiency in the soil of southern Iran. When selenium was given, it resulted in the fast recovery of the affected neonatal lambs. Moreover, no further cases of this disease (WMD) were reported after such treatments.

Selenium and white muscle disease in woodchucks.

Gross and histologic examination of wood chcks (Marmota monax) trapped on farms in Central New York revealed white muscle disease(WMD). The concentration of selenium in the animal tissues, vegetation and soils in the vicinity of trapping did not consistently correlate with the presence of WMD.