The molecular mechanisms linking obstructive sleep apnea (OSA) with type 2 diabetes mellitus (T2DM) remain unclear. This study investigated the effect of OSA on skeletal muscle lipid oxidation in nondiabetic controls and in type 2 diabetes (T2DM) patients. Forty-four participants matched for age and adiposity were enrolled: nondiabetic controls (control, n = 14), nondiabetic patients with severe OSA (OSA, n = 9), T2DM patients with no OSA (T2DM, n = 10), and T2DM patients with severe OSA (T2DM + OSA, n = 11). A skeletal muscle biopsy was performed; gene and protein expressions were determined and lipid oxidation was analyzed. An intravenous glucose tolerance test was performed to investigate glucose homeostasis. No differences in lipid oxidation (178.2 ± 57.1, 161.7 ± 22.4, 169.3 ± 50.9, and 140.0 ± 24.1 pmol/min/mg for control, OSA, T2DM, and T2DM+OSA, respectively; p > 0.05) or gene and protein expressions were observed between the groups. The disposition index, acute insulin response to glucose, insulin resistance, plasma insulin, glucose, and HBA1C progressively worsened in the following order: control, OSA, T2DM, and T2DM + OSA (p for trend <0.05). No association was observed between the muscle lipid oxidation and the glucose metabolism variables. We conclude that severe OSA is not associated with reduced muscle lipid oxidation and that metabolic derangements in OSA are not mediated through impaired muscle lipid oxidation.

• MeSH
• diabetes mellitus 2. typu * komplikace   metabolismus   MeSH
• glukosa metabolismus   MeSH
• inzulinová rezistence * MeSH
• inzuliny * MeSH
• lidé MeSH
• lipidy MeSH
• obstrukční spánková apnoe * metabolismus   MeSH
• polysomnografie MeSH
• svaly metabolismus   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Interleukin-35 (IL-35) is a recently described heterodimeric cytokine that belongs to the IL-12 family and consists of p35 (IL-12a) and EBI3 (IL-27b) subunits. The expression of IL-35 in humans is inducible in response to inflammatory stimuli. Increased IL-35 levels were documented in several autoimmune inflammatory diseases, suggesting a possible immunomodulatory role in their pathogenesis. OBJECTIVES: The aim of this study was to explore a potential role of IL-35 in the pathogenesis of idiopathic inflammatory myopathies (IIM) by studying the expression of IL-35 subunits in muscle biopsy samples and by evaluating serum levels of IL-35 and their association with disease activity in IIM patients. METHODS: The expression of IL-35 subunits was studied in serial sections of 9 muscle biopsy samples [4 polymyositis (PM), 5 dermatomyositis (DM)] and in 7 non-inflammatory control muscle biopsies. Serum levels of IL-35 were measured in 23 PM, 28 DM and 15 cancer associated myositis (CAM) patients as well as in 40 healthy controls. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT) and by serum muscle enzymes. RESULTS: Expression of both IL-35 subunits was evident in the inflammatory infiltrates in IIM muscle biopsies, while no IL-35 expression was observed in control muscle samples. IL-35 serum levels were increased in all IIM patients compared to healthy controls [median 119.5 (range 32.1-1074.5) vs 36.2 (range 1.5-86.5) pg/ml, P < 0.001]. There were no differences in IL-35 serum levels between myositis subgroups (DM, PM or CAM). Serum IL-35 levels correlated significantly with physician's assessment of global (r = 0.29, p = 0.021), muscle (r = 0.30, p = 0.017) and extramuscular (r = 0.30, p = 0.016) disease activity as well as creatine kinase (r = 0.26, p = 0.044) and lactate dehydrogenase (r = 0.40, p = 0.003) levels. There was a significant correlation with pulmonary activity in patients with interstitial lung disease (r = 0.39, p = 0.037). Serum IL-35 correlated negatively with duration of treatment (r = -34, p = 0.009). CONCLUSIONS: IL-35 is overexpressed in inflammatory infiltrates in muscle tissue and serum in IIM patients and there is correlation with several disease activity parameters. These data suggest potential role of locally produced IL-35 in the pathogenesis of inflammatory myopathies.

• MeSH
• biopsie MeSH
• dítě MeSH
• dospělí MeSH
• interleukiny krev   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myozitida krev   metabolismus   patologie   MeSH
• polymyozitida krev   metabolismus   patologie   MeSH
• senioři MeSH
• svaly metabolismus   patologie   MeSH
• upregulace MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• lidé MeSH
• pohyb fyziologie   MeSH
• svaly * fyziologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Despite the importance of drug release testing of parenteral depot formulations, the current in vitro methods still require ameliorations in biorelevance. We have investigated here the use of muscle tissue components to better mimic the intramuscular administration. For convenient handling, muscle tissue was used in form of a freeze-dried powder, and a reproducible process of incorporation of tested microspheres to an assembly of muscle tissue of standardized dimensions was successfully developed. Microspheres were prepared from various grades of poly(lactic-co-glycolic acid) (PLGA) or ethyl cellulose, entrapping flurbiprofen, lidocaine, or risperidone. The deposition of microspheres in the muscle tissue or addition of only isolated lipids into the medium accelerated the release rate of all model drugs from microspheres prepared from ester-terminated PLGA grades and ethyl cellulose, however, not from the acid-terminated PLGA grades. The addition of lipids into the release medium increased the solubility of all model drugs; nonetheless, also interactions of the lipids with the polymer matrix (ad- and absorption) might be responsible for the faster drug release. As the in vivo drug release from implants is also often faster than in simple buffers in vitro, these findings suggest that interactions with the tissue lipids may play an important role in these still unexplained observations.

• MeSH
• celulosa analogy a deriváty   MeSH
• flurbiprofen aplikace a dávkování   MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• léky s prodlouženým účinkem * MeSH
• lidokain aplikace a dávkování   MeSH
• mikrosféry MeSH
• nosiče léků MeSH
• parenterální infuze * MeSH
• pomocné látky MeSH
• prasata MeSH
• příprava léků MeSH
• risperidon aplikace a dávkování   MeSH
• svaly metabolismus   MeSH
• techniky in vitro MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Histidine (HIS) is investigated for therapy of various disorders and as a nutritional supplement to enhance muscle performance. We examined effects of HIS on amino acid and protein metabolism. Rats consumed HIS in a drinking water at a dose of 0.5 g/l (low HIS), 2 g/l (high HIS) or 0 g/l (control) for 4 weeks. At the end of the study, the animals were euthanized and blood plasma, liver, soleus (SOL), tibialis (TIB), and extensor digitorum longus (EDL) muscles analysed. HIS supplementation increased food intake, body weight and weights and protein contents of the liver and kidneys, but not muscles. In blood plasma there were increases in glucose, urea, and several amino acids, particularly alanine, proline, aspartate, and glutamate and in high HIS group, ammonia was increased. The main findings in the liver were decreased concentrations of methionine, aspartate, and glycine and increased alanine. In muscles of HIS-consuming animals increased alanine and glutamine. In high HIS group (in SOL and TIB) increased chymotrypsin-like activity of proteasome (indicates increased proteolysis); in SOL decreased anserine (beta-alanyl-N1-methylhistidine). We conclude that HIS supplementation increases ammonia production, alanine and glutamine synthesis in muscles, affects turnover of proteins and HIS-containing peptides, and increases requirements for glycine and methionine.

• MeSH
• aminokyseliny metabolismus   MeSH
• histidin aplikace a dávkování   MeSH
• játra metabolismus   MeSH
• náhodné rozdělení MeSH
• potkani Wistar MeSH
• potravní doplňky MeSH
• proteasomový endopeptidasový komplex metabolismus   MeSH
• svaly metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are increased in starvation and diabetes mellitus. However, the pathogenesis has not been explained. It has been shown that BCAA catabolism occurs mostly in muscles due to high activity of BCAA aminotransferase, which converts BCAA and α-ketoglutarate (α-KG) to branched-chain keto acids (BCKAs) and glutamate. The loss of α-KG from the citric cycle (cataplerosis) is attenuated by glutamate conversion to α-KG in alanine aminotransferase and aspartate aminotransferase reactions, in which glycolysis is the main source of amino group acceptors, pyruvate and oxaloacetate. Irreversible oxidation of BCKA by BCKA dehydrogenase is sensitive to BCKA supply, and ratios of NADH to NAD+ and acyl-CoA to CoA-SH. It is hypothesized that decreased glycolysis and increased fatty acid oxidation, characteristic features of starvation and diabetes, cause in muscles alterations resulting in increased BCAA levels. The main alterations include (i) impaired BCAA transamination due to decreased supply of amino groups acceptors (α-KG, pyruvate, and oxaloacetate) and (ii) inhibitory influence of NADH and acyl-CoAs produced in fatty acid oxidation on citric cycle and BCKA dehydrogenase. The studies supporting the hypothesis and pros and cons of elevated BCAA concentrations are discussed in the article.

• MeSH
• alanin metabolismus   MeSH
• diabetes mellitus metabolismus   MeSH
• glykolýza MeSH
• hladovění metabolismus   MeSH
• inzulin metabolismus   MeSH
• inzulinová rezistence MeSH
• kyseliny ketoglutarové metabolismus   MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• obezita metabolismus   MeSH
• oxidace-redukce MeSH
• pyruváty farmakokinetika   MeSH
• svaly enzymologie   metabolismus   MeSH
• transaminasy metabolismus   MeSH
• větvené aminokyseliny metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This study tested the hypothesis that in human aging, a decreased intramuscular acylcarnitine status is associated with (pre-)frailty, reduced physical performance, and altered mitochondrial function. We used a cross-sectional study design with well-matched fit and (pre-)frail old males and females, using young males and females as healthy controls. Frailty was assessed according to the Fried criteria and physical performance was determined by 400 m walk test, short physical performance battery and handgrip strength. Muscle and plasma acylcarnitine status, and muscle mitochondrial gene expression was analyzed. Results showed that intramuscular total carnitine levels and short-chain acylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. The low intramuscular short-chain acylcarnitine levels in females correlated with low physical performance, even after correction for muscle mass (%), and were accompanied with lowered expression of genes involved in mitochondrial energy production and functionality. It is, therefore, concluded that in (pre-)frail old females, intramuscular total carnitine levels and short-chain acylcarnitine levels are decreased, and this decrease is associated with reduced physical performance and low expression of a wide range of genes critical for mitochondrial function. The results stress the importance of taking sex differences into account in aging research.

• MeSH
• chůze fyziologie   MeSH
• karnitin analogy a deriváty   krev   chemie   metabolismus   MeSH
• křehkost metabolismus   patofyziologie   MeSH
• křehký senior MeSH
• lidé MeSH
• průřezové studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sexuální faktory MeSH
• síla ruky fyziologie   MeSH
• stárnutí metabolismus   fyziologie   MeSH
• svaly metabolismus   MeSH
• tělesná výkonnost fyziologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Circulating miRNAs have been proposed as the effective diagnostic biomarkers for muscular fibrosis-associated diseases. However, circulating biomarkers for early diagnosis of contracture muscles are limited in gluteal muscle contracture (GMC) patients. Here we sought to explore the abnormally expressed miRNAs in plasma and contraction bands of GMC patients. The results showed miR-29a-3p expression in plasma and contraction bands tissue was significantly reduced in GMC patients compared with normal control. Cell viability and levels of proliferation-associated protein cyclin D1 and cyclin-dependent-kinase 2 (CDK2) were powerfully inhibited by miR-29a mimics and enhanced by miR-29a inhibitor compared with negative control. Furthermore, miR-29a mimics effectively impeded, while miR-29a inhibitor enhanced the expression of collagen I and collagen III, followed by the secretion of transforming growth factor beta1 (TGF-beta1), TGF-beta3 and connective tissue growth factor (CTGF) in primary human contraction bands (CB) fibroblasts. The miR-29a-3p negatively regulated the expression of TGF-beta1 through binding to the 3´ UTR region of SERPINH1 (encoding heat shock protein HSP47), but had no effect on Smad2 activity. The miR-29a-3p was inversely correlated with HSP47 in contraction bands tissue from GMC patients. Collectively, miR-29a was notably depressed and regulated cell viability and fibrosis by directly targeting HSP47 in GMC, which suggest that circulating miR-29a might be a potential biomarker for early diagnosis and provides a novel therapeutic target for GMC.

• MeSH
• biologické markery metabolismus   MeSH
• dospělí MeSH
• fibroblasty metabolismus   patologie   MeSH
• fibróza genetika   patologie   prevence a kontrola   MeSH
• hýždě patologie   MeSH
• kontraktura genetika   patologie   prevence a kontrola   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• proteiny tepelného šoku HSP47 genetika   metabolismus   MeSH
• studie případů a kontrol MeSH
• svaly metabolismus   patologie   MeSH
• transformující růstový faktor beta1 genetika   metabolismus   MeSH
• viabilita buněk fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Type I diabetes mellitus (DM1) is a complex disease with adverse effects on organs and tissues despite compensation by insulin treatment. The goal of our study was to study how kidney diseases change (31)P MR parameters of muscle metabolism in DM1 patients with respect to gender. 51 DM1 patients (19 m/14 f without and 13 m/5 f with nephropathy) and 26 (14 m/12 f) healthy volunteers were examined using (31)P magnetic resonance spectroscopy at 3T tomograph at rest, and during and after a calf muscle exercise. The exercise consisted of a six-minute plantar flexion using a pedal ergometer followed by a six-minute recovery. It is reflected by reduced relative beta-ATP and increased Pi and phosphodiester signals to phosphocreatine (PCr) at rest and prolongation of the PCr recovery time after the exercise. Measurement on healthy volunteers indicated differences between males and females in pH at the rest and after the exercise only. These differences between patients groups were not significant. We have proven that nephropathy affects the metabolism in diabetic patients and our results confirm significant difference between patients with and without nephropathy. Gender differences in pH were observed only between male and female healthy volunteers.

• MeSH
• diabetes mellitus 1. typu komplikace   metabolismus   MeSH
• diabetické nefropatie etiologie   metabolismus   MeSH
• dospělí MeSH
• energetický metabolismus MeSH
• izotopy fosforu MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• mladý dospělý MeSH
• sexuální faktory MeSH
• studie případů a kontrol MeSH
• svaly metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The aim of this research was to determine the concentrations of cadmium, lead, mercury, and arsenic and the essential elements iron and selenium in the tissues (muscle, kidney, liver, spleen, and fat) of fallow deer (Dama dama L.) without and with supplemental selenium addition. Another aim was to determine the effect of selenium addition on the indicators of oxidative stress, namely, the levels of superoxide dismutase, glutathione peroxidase, glutathione, and vitamin E. The research was carried out with 40 fallow deer during two research periods. Supplemental feed without selenium addition was provided during the first research period, and supplemental feed with added selenium (3 mg/kg) was provided for 60 days during the second research period. The concentration of selenium in tissues was higher in the second research period than in the first research period (in kidney tissue, 0.957 vs. 0.688 mg/kg, P < 0.05). The dietary addition of selenium decreased (P < 0.05) the concentrations of some heavy metals (lead in the spleen = 0.06 vs. 0.27 mg/kg and in the fatty tissue = 0.17 vs. 0.69 mg/kg; arsenic in the muscle tissue = 0.005 vs. 0.014 mg/kg, liver = 0.003 vs. 0.009 mg/kg, spleen = 0.004 vs. 0.013 mg/kg, and fat = 0.008 vs. 0.016 mg/kg). The activity of glutathione peroxidase was significantly higher (P < 0.05) in the second research period than in the first research period (1375.36 vs. 933.23 U/L).

• MeSH
• arsen MeSH
• dieta MeSH
• glutathionperoxidasa krev   metabolismus   MeSH
• játra chemie   metabolismus   MeSH
• kadmium MeSH
• ledviny chemie   MeSH
• orgánová specificita účinky léků   MeSH
• rtuť MeSH
• selen analýza   krev   MeSH
• slezina chemie   metabolismus   MeSH
• svaly chemie   metabolismus   MeSH
• vitamin E MeSH
• vysoká zvěř krev   MeSH
• železo MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Chorvatsko MeSH