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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This book is a concise summary of the present knowledge about skeletal muscle fibres. The fibre types were characterized from different points of view. The difficulties and possibilities of classifying muscle fibres in distinct non-overlapping types were shown. A main emphasis is put on metabolic fibre typing by cytophotometry as well as the adaptability of a given fibre type to altered physiological and pathological conditions. Extensive analyses of several rat hindlimb muscles revealed regional differences of fibre properties within the muscles and showed the influence of ageing, myopathy, hypoxia, diabetes and Ginkgo biloba-treatment on the different fibre types. The plasticity of muscle fibres was demonstrated by the flexibility of fibre metabolism as an adaptive mechanism.
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PMID:Fibre types in skeletal muscles. 1189 40

Enteroviral persistence has been implicated in the pathogenesis of several chronic human diseases, including dilated cardiomyopathy, insulin-dependent diabetes mellitus, and chronic inflammatory myopathy. However, these viruses are considered highly cytolytic, and it is unclear what mechanisms might permit their long-term survival. Here, we describe the generation of a recombinant coxsackievirus B3 (CVB3) expressing the enhanced green fluorescent protein (eGFP), which we used to mark and track infected cells in vitro. Following exposure of quiescent tissue culture cells to either wild-type CVB3 or eGFP-CVB3, virus production was very limited but increased dramatically after cells were permitted to divide. Studies with cell cycle inhibitors revealed that cells arrested at the G(1) or G(1)/S phase could express high levels of viral polyprotein and produced abundant infectious virus. In contrast, both protein expression and virus yield were markedly reduced in quiescent cells (i.e., cells in G(0)) and in cells blocked at the G(2)/M phase. Following infection with eGFP-CVB3, quiescent cells retained viral RNA for several days in the absence of infectious virus production. Furthermore, RNA extracted from nonproductive quiescent cells was infectious when transfected into dividing cells, indicating that CVB3 appears to be capable of establishing a latent infection in G(0) cells, at least in tissue culture. Finally, wounding of infected quiescent cells resulted in viral protein expression limited to cells in and adjacent to the lesion. We suggest that (i) cell cycle status determines the distribution of CVB3 during acute infection and (ii) the persistence of CVB3 in vivo may rely on infection of quiescent (G(0)) cells incapable of supporting viral replication; a subsequent change in the cell cycle status may lead to virus reactivation, triggering chronic viral and/or immune-mediated pathology in the host.
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PMID:Cell cycle status affects coxsackievirus replication, persistence, and reactivation in vitro. 1193 10

A 57 year-old man with a history of diabetes mellitus was admitted to our hospital for the complaint of slowly progressive muscle weakness involving proximal limbs and head dropping. His serum CK level was within normal range, and muscle biopsy showed no inflammatory changes. To rule out myasthenia gravis, computerized tomography was done for the detection of thymoma, and detected an adrenal tumor in stead. He was not over-weighted, and his morning plasma levels of ACTH and cortisol were within normal ranges. Additional hormonal examinations revealed daily autonomous hypersecretion of cortisol. He received diagnosis of preclinical Cushing syndrome. After resection of the tumor, muscle weakness improved and his diabetes mellitus was controlled better. The muscle symptoms seem to be related with steroid myopathy. Preclinical Cushing syndrome should be included as a differential diagnosis for myopathy of unknown etiology.
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PMID:[A patient with myopathy due to preclinical Cushing syndrome]. 1196 44

Mutations in mitochondrial genes encoded by both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA have been implicated in a wide range of degenerative diseases. MtDNA base substitution and rearrangement mutations can cause myopathy, cardiomyopathy, ophthalmological defects, growth retardation, movement disorders, dementias, and diabetes. nDNA mutations can affect mtDNA replication and transcription, increase mtDNA mutations through defects in the adenine nucleotide translocator isoform 1 (ANT1), or cause Leigh's syndrome, as a result of defects in oxidative phosphorylation (OXPHOS) structural genes. Mouse models of mtDNA base substitution mutations have been created by introducing the mtDNA 16S rRNA chloramphenicol (CAP)-resistance mutation into the mouse female germline. This resulted in ophthalmological defects in chimeras and perinatal lethality resulting from myopathy and cardiomyopathy in mutant animals. Mouse models of mtDNA rearrangements have resulted in animals with myopathy, cardiomyopathy, and nephropathy. Conditional inactivation of the mouse nDNA mitochondrial transcription factor (Tfam) gene in the heart caused neonatal lethal cardiomyopathy, whereas its inactivation in the pancreatic beta-cells caused diabetes. Mutational inactivation of the mouse Ant1 gene resulted in myopathy, cardiomyopathy, and multiple mtDNA deletions in association with elevated reactive oxygen species (ROS) production. This suggests that multiple mtDNA deletion syndrome can be caused by increased ROS damage. The inactivation of the uncoupler protein genes (Ucp) 1-3 resulted in alterations in delta mu H+ and increased ROS production. Inactivation of the Ucp2 gene, which is expressed in the pancreatic beta-cells, resulted in increased islet ATP, increased serum insulin levels, and suppression of the diabetes of the ob/ob mouse genotype. Transgenic mice with altered beta-cell ATP-sensitive K+ channels (KATP) also developed diabetes. Mutational inactivation of the mitochondrial antioxidant genes for glutathione peroxidase (GPx1) and Mn superoxide dismutase (Sod2) caused reduced energy production and neonatal lethal dilated cardiomyopathy, respectively, the later being ameliorated by treatment with MnSOD mimics. Partial Sod2 deficiency (+/-) resulted in mice with increased mitochondrial damage during aging, and treatment of C. elegans with catalytic antioxidant drugs can extend their life-span. Mice deficient in cytochrome-c died early in embryogenesis, but cells derived from these embryos had a complete deficiency in mitochondrial apoptosis. Mice lacking the proapoptotic Bax and Bak genes were not able to release cytochrome-c from the mitochondrion and were blocked in apoptosis. Mice lacking Apaf1, Cas9, and Cas3 did release mitochondrial cytochrome-c and were blocked in the downstream steps of apoptosis. These animal studies confirm that alterations in mitochondrial energy generation, ROS production, and apoptosis can all contribute to the pathophysiology of mitochondrial disease.
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PMID:Animal models for mitochondrial disease. 1201 5

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS) is a maternally inherited multisystem disease caused by mutations of the mitochondrial DNA. The characteristic clinical features are: encephalopathy manifesting as dementia and seizures, stroke-like episodes at young age (usually < 40), lactic acidosis and myopathy with ragged-red fibres. Other frequent manifestations include: sensorineural deafness, diabetes, hypoparathyroidism, peripheral neuropathy and cardiomyopathy. We present two patients with MELAS who were diagnosed 4 and 9 years respectively following the onset of the disease despite the characteristic clinical pictures. The differential diagnostics of inborn and acquired disorders causing stroke is included. We regard that mitochondrial diseases are still insufficiently known and are frequently misdiagnosed. The knowledge is indispensable for establishing diagnosis and accurate genetic counselling. Although there is no specific therapy for mitochondrial diseases to date, coenzyme Q and various vitamins as well as moderate degree exercise might be recommended.
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PMID:[MELAS--mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome--two cases confirmed by biochemical and molecular investigations. Differential diagnosis of stroke causes]. 1218 2

We investigated distribution of HLA class II alleles among 52 unrelated patients with dilated cardiomyopathy (DCM) (25 consecutive men, 27 consecutive women, mean age 38 +/- 16 years) to determine if there is any immunogenetic predisposition to the disease. DCM was diagnosed according to WHO criteria. HLA-DR and DQ alleles were examined by PCR-SSP typing. Frequency of DRB1* and DQB1* alleles in the study group was compared to local control group (n = 126 for DRB1* and n = 76 for DQB1* alleles). There was a non-significant increase in the frequency of HLA-DRB1*03 (chi square = 4.78, p < 0.05, p corrected for multiple comparisons (pcorr)--NS) and HLA-DQB1*02 (chi square = 4.92, p < 0.05, pcorr--NS) among DCM patients as compared to controls. Frequency of DRB1*04 allele was lower than expected (chi square = 4.58, p < 0.05, pcorr--NS). DRB1*03 is associated with several autoimmune diseases, of interest it confers risk for idiopathic myopathy in Polish patients. Heterozygosity for DRB1*03/DRB1*04, known for association with insulin-dependent diabetes mellitus was found in 3 patients (5.7%), two of them had adult-onset insulin-dependent diabetes mellitus. There was a tendency to overrepresentation of DRB1*08 among men with DCM. In conclusion, these data give some support for autoimmune involvement in the pathogenesis of dilated cardiomyopathy.
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PMID:[Frequency of DRB1* and DQB1* alleles in Polish patients with dilated cardiomyopathy]. 1236 98

Lower limb compartment syndrome is an unusual but severe complication of prolonged surgery more than four hours in lithotomy position. It is usually a consequence of hypoperfusion of the lower extremities and muscle necrosis may occur. Several risk factors are pointed out: trendelenburg, the hardness of operating table, hypothermia, control hypotension, occlusion of arterial blood flow of the lower extremity, arteritis (and smoking), diabetes, obesity, arterial hypertension, myopathy and an important muscle mass. The symptoms are postoperative pain with neurological signs. A rapid diagnosis and aggressive management (i.e. resuscitation and aponevrotomy) is recommended. Neurological sequelae are sometimes invalidating. Reporting a case of bilateral syndrome, we reviewed the literature and describe the present diagnosis and therapeutic management as well as prevention modalities of this iatrogenic complication.
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PMID:[Bilateral compartment syndrome after colorectal surgery in the lithotomy position]. 1240 49

20,536 adults (15,454 men and 5,082 women, aged 40-80 years) with coronary heart disease, other occlusive arterial disease or diabetes mellitus were randomly allocated to receive 40 mg simvastatin daily or matching placebo. In addition to being randomized to compare simvastatin vs placebo, all patients were also randomized to compare antioxidant vitamin supplementation (vitamin E 600 mg/day, vitamin C 250 mg/day and betacarotene 20 mg/day) vs placebo in a "2 x 2 factorial" design. Duration of the study was 5 years. All-cause mortality was significantly reduced among patients allocated to simvastatin (-12.3%) due to a highly significant (-18%) reduction in the coronary death rate, a marginally significant reduction in other vascular deaths and a non-significant reduction in non-vascular deaths. There were highly significant reductions (of about one-quarter) in the first event rate for non-fatal myocardial infarction and coronary death (combined), for non-fatal and fatal stroke and for coronary or non-coronary revascularization. The beneficial effect of simvastatin was seen in all sub-categories which were studied and, particularly: women vs men; patients aged > 70 years vs those aged < 70 years; patients with LDL cholesterol < vs > 116 mg/dl, or total cholesterol < vs > 193 mg/dl. The treatment was well tolerated and the annual risk of myopathy was 0.01%. All comparisons between antioxidant vitamin supplementation and placebo failed to reveal any difference in favour or against the supplementation which was otherwise well tolerated. These important results and their implications will be briefly discussed.
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PMID:[Clinical study of the month. The MRC/BHF Heart Protection Study]. 1244 Mar 52

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are associated with skeletal muscle complaints, including clinically important myositis and rhabdomyolysis, mild serum creatine kinase (CK) elevations, myalgia with and without elevated CK levels, muscle weakness, muscle cramps, and persistent myalgia and CK elevations after statin withdrawal. We performed a literature review to provide a clinical summary of statin-associated myopathy and discuss possible mediating mechanisms. We also update the US Food and Drug Administration (FDA) reports on statin-associated rhabdomyolysis. Articles on statin myopathy were identified via a PubMed search through November 2002 and articles on statin clinical trials, case series, and review articles were identified via a PubMed search through January 2003. Adverse event reports of statin-associated rhabdomyolysis were also collected from the FDA MEDWATCH database. The literature review found that reports of muscle problems during statin clinical trials are extremely rare. The FDA MEDWATCH Reporting System lists 3339 cases of statin-associated rhabdomyolysis reported between January 1, 1990, and March 31, 2002. Cerivastatin was the most commonly implicated statin. Few data are available regarding the frequency of less-serious events such as muscle pain and weakness, which may affect 1% to 5% of patients. The risk of rhabdomyolysis and other adverse effects with statin use can be exacerbated by several factors, including compromised hepatic and renal function, hypothyroidism, diabetes, and concomitant medications. Medications such as the fibrate gemfibrozil alter statin metabolism and increase statin plasma concentration. How statins injure skeletal muscle is not clear, although recent evidence suggests that statins reduce the production of small regulatory proteins that are important for myocyte maintenance.
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PMID:Statin-associated myopathy. 1292 63

Updated guidelines from the National Cholesterol Education Program give greater emphasis to lipoproteins other than low-density lipoprotein cholesterol (LDL) than previous guidelines. Although statins remain first-line therapy for most patients to lower LDL, combination therapy is the next logical step in achieving goals in patients with mixed dyslipidemia or elevated LDL despite statin therapy. As the prevalence of diabetes, metabolic syndrome, and atherogenic dyslipidemia rises, the importance of treating the total lipid profile becomes even more crucial. Niacin, fibrates, and bile acid sequestrants are effective in combination with statins in lowering LDL, triglycerides, and total cholesterol levels and increasing high-density lipoprotein cholesterol (HDL). Although combination therapies may increase the risk of myopathy, both fibrate-statin and niacin-statin combinations are considered safe. In addition, niacin-statin therapy reduces atherosclerotic progression and coronary events. New pharmacologic formulations exist that will further affect treatment: a single-tablet combination of lovastatin and extended-release niacin is available, as is ezetimibe, a cholesterol-absorption inhibitor. In all, both HDL and triglyceride levels correlate with cardiovascular risk and should be considered secondary targets of therapy. Combination therapy can be safe and effective and can be constructed to affect all lipoprotein parameters.
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PMID:Treating dyslipidemic patients with lipid-modifying and combination therapies. 1274 37


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