Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymerase I and transcript release factor (Ptrf, also known as Cavin1) is an essential component in the biogenesis and function of caveolae. Ptrf knockout mice or patients with PTRF mutations exhibit numerous pathologies including markedly aberrant fuel metabolism, lipodystrophy and muscular dystrophy. In this study, we generated Ptrf transgenic mice to explore its function in vivo. Compared with wild-type (WT) mice, we found that the Ptrf transgenic mice showed obesity with an increased level of ALT (alanine aminotransferase) and AST (aspartate transaminase). Ptrf transgenic mice exhibited severe fat degeneration and a higher degree of fat accumulation in the liver compared with WT mice. Consistently, we found that the expression of the fat synthesis gene, Fasn, was increased in the liver of Ptrf transgenic mice. Thus, Ptrf transgenic mice would be a good model for investigating the molecular mechanism and therapeutic targets of obesity and fatty liver associated diseases.
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PMID:Ptrf transgenic mice exhibit obesity and fatty liver. 2938 31

Serum activities of alanine and aspartate aminotransferases (ALT and AST) are used as gold standard biomarkers for the diagnosis of hepatocellular injury. Since ALT and AST lack liver specificity, the diagnosis of the onset of hepatocellular injury in patients with underlying muscle impairments is severely limited. Thus, we evaluated the potential of glutamate dehydrogenase (GLDH) as a liver specific alternative biomarker of hepatocellular injury. In our study, serum GLDH in subjects with Duchene muscular dystrophy (DMD) was equivalent to serum GLDH in age matched healthy subjects, while serum ALT was increased 20-fold in DMD subjects. Furthermore, serum GLDH in 131 subjects with variety of muscle impairments was similar to serum GLDH of healthy subjects while serum ALT corelated with serum creatine kinase, a widely accepted biomarker of muscle impairment. In addition, significant elevations of ALT, AST, and CK were observed in a case of a patient with rhabdomyolysis, while serum GLDH stayed within the normal range until the onset of hypoxia-induced liver injury. In a mouse model of DMD (DMDmdx), serum GLDH but not serum ALT clearly correlated with the degree of acetaminophen-induced liver injury. Taken together, our data support the utility of serum GLDH as a liver-specific biomarker of liver injury that has a potential to improve diagnosis of hepatocellular injury in patients with underlying muscle impairments. In drug development, GLDH may have utility as a biomarker of drug induced liver injury in clinical trials of new therapies to treat muscle diseases such as DMD.
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PMID:Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments. 3240 33

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.
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PMID:The influence of selenium deficiency on chosen biochemical parameters and histopathological changes in muscles of goat kids. 3262 85


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