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Sample records for involve liver muscle

  1. Pterostilbene improves glycaemic control in rats fed an obesogenic diet: involvement of skeletal muscle and liver.

    PubMed

    Gómez-Zorita, S; Fernández-Quintela, A; Aguirre, L; Macarulla, M T; Rimando, A M; Portillo, M P

    2015-06-01

    This study aims to determine whether pterostilbene improves glycaemic control in rats showing insulin resistance induced by an obesogenic diet. Rats were divided into 3 groups: the control group and two groups treated with either 15 mg kg(-1) d(-1) (PT15) or 30 mg kg(-1) d(-1) of pterostilbene (PT30). HOMA-IR was decreased in both pterostilbene-treated groups, but this reduction was greater in the PT15 group (-45% and -22% respectively vs. the control group). The improvement of glycaemic control was not due to a delipidating effect of pterostilbene on skeletal muscle. In contrast, GLUT4 protein expression was increased (+58% and +52% vs. the control group), suggesting an improved glucose uptake. The phosphorylated-Akt/total Akt ratio was significantly enhanced in the PT30 group (+25%), and therefore a more efficient translocation of GLUT4 is likely. Additionally, in this group the amount of cardiotrophin-1 was significantly increased (+65%). These data suggest that the effect of pterostilbene on Akt is mediated by this cytokine. In the liver, glucokinase activity was significantly increased only in the PT15 group (+34%), and no changes were observed in glucose-6-phosphatase activity. The beneficial effect of pterostilbene on glycaemic control was more evident with the lower dose, probably because in the PT15 group both the muscle and the liver were contributing to this effect, but in the PT30 group only the skeletal muscle was responsible. In conclusion, pterostilbene improves glycaemic control in rats showing insulin resistance induced by an obesogenic diet. An increase in hepatic glucokinase activity, as well as in skeletal muscle glucose uptake, seems to be involved in the anti-diabetic effect of this phenolic compound.

  2. Liver involvement in systemic infection

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2014-01-01

    The liver is often involved in systemic infections, resulting in various types of abnormal liver function test results. In particular, hyperbilirubinemia in the range of 2-10 mg/dL is often seen in patients with sepsis, and several mechanisms for this phenomenon have been proposed. In this review, we summarize how the liver is involved in various systemic infections that are not considered to be primarily hepatotropic. In most patients with systemic infections, treatment for the invading microbes is enough to normalize the liver function tests. However, some patients may show severe liver injury or fulminant hepatic failure, requiring intensive treatment of the liver. PMID:25276279

  3. Muscle cramps in liver disease.

    PubMed

    Mehta, Shivang S; Fallon, Michael B

    2013-11-01

    Muscle cramps are common in patients with liver disease and adversely influence quality of life. The exact mechanisms by which they occur remain unclear, although a number of pathophysiological events unique to liver disease may contribute. Clinical studies have identified alterations in 3 areas: nerve function, energy metabolism, and plasma volume/electrolytes. Treatments have focused on these particular areas with varied results. This review will focus on the clinical features of muscle cramps in patients with liver disease and review potential mechanisms and current therapies.

  4. [Liver involvement in lymphogranulomatosis].

    PubMed

    Hanke, P; Sickel, W; Stenzel, L; Krug, K; Roedel, G; Rath, F W

    1979-07-15

    Of 146 patients with lymphogranulomatosis biochemical parameters were tested for their diagnostic valency concerning the recognition of a liver infiltration. In patients with histologically proved affection of the liver the AP, GGTP, AAP, LAP and LDH show a significant increase in comparison to the enzyme values of the patients without any hepatic manifestation. In an increased result of 4 enzyme values with a probability of 85% muste be reckoned with a participation of the liver. The enzyme SGOT, SGPT, GDH, LDH-isoenzymes, choline esterase, beta-GC, the De Ritis quotient and the quotient (Formula: see text), on the other hand, do not give any additional differential-diagnostic information.

  5. Effect of dietary fish oil on the expression of genes involved in lipid metabolism in liver and skeletal muscle of lactating sows.

    PubMed

    Gessner, D K; Gröne, B; Rosenbaum, S; Most, E; Hillen, S; Becker, S; Erhardt, G; Reiner, G; Eder, K

    2016-04-01

    This study investigated the hypothesis that dietary supplementation of fish oil as a source of n-3 polyunsaturated fatty acids (PUFA) influences the expression of target genes of sterol regulatory element-binding proteins (SREBP)-1 and (SREBP)-2 involved in triacylglycerol (TAG) synthesis and fatty acid and cholesterol metabolism in the liver, and moreover activates the expression of target genes of peroxisome proliferation-activated receptor (PPAR)-α involved in TAG and fatty acid catabolism in liver and skeletal muscle. Twenty lactating sows were fed a control diet or a fish oil diet with either 50 g of a mixture of palm oil and soya bean oil (4:1, w/w) or fish oil per kg. The diet of the fish oil group contained 19.1 g of n-3 PUFA (mainly 20:5 n-3 and 22:6 n-3) per 100 g of total fatty acids, while the diet of the control group contained 2.4 g of n-3 PUFA (mainly 18:3 n-3) per 100 g of total fatty acids. The fish oil group had reduced relative mRNA concentrations of various target genes of SREBP-1 involved in fatty acid and TAG synthesis in comparison with the control group (p < 0.05). Relative mRNA concentrations of target genes of PPARα involved in fatty acid catabolism in both liver and muscle, and mRNA concentrations of target genes of SREBP-2 involved in cholesterol synthesis and uptake were not influenced by fish oil supplementation. Concentrations of cholesterol and TAG in plasma, fat content of milk and weight gains of litters during the suckling period were not different between the two groups of sows. In conclusion, this study suggests that fish oil has only minor effects on hepatic lipid metabolism, which are non-critical with respect to milk production in sows. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  6. Malignant haemangioendothelioma involving the liver

    PubMed Central

    Pollard, Stella M.; Millward-Sadler, G. H.

    1974-01-01

    The features of four cases of malignant haemangioendothelioma involving the liver and other organs are described. Two cases were associated with a microangiopathic haemolytic anaemia. The nature of the tumours and possible pathogenesis for the anaemias are discussed. Images PMID:4832301

  7. Liver involvement in Langerhans cell histiocytosis.

    PubMed

    Wong, Adelaine; Ortiz-Neira, Clara L; Reslan, Walid Abou; Sharon, Raphael; Pinto-Rojas, Alfredo; Kaura, Deepak; Anderson, Ronald

    2006-10-01

    Liver involvement in Langerhans cell histiocytosis (LCH) typically presents with hepatomegaly and other signs of liver dysfunction. We present an 11-month-old child having only minimally elevated liver enzymes as an indication of liver involvement. Using sonography as the initial diagnostic tool followed by MRI, LCH of the liver was revealed. A review of sonographic, CT, MRI and MR cholangiopancreatography findings in liver LCH is presented. We recommend that physicians consider sonography and MRI screening for liver involvement in patients with newly diagnosed LCH, as periportal involvement may be present with little or no liver function abnormality present, as in this patient.

  8. Muscle mass predicts outcomes following liver transplantation.

    PubMed

    DiMartini, Andrea; Cruz, Ruy J; Dew, Mary Amanda; Myaskovsky, Larissa; Goodpaster, Bret; Fox, Kristen; Kim, Kevin H; Fontes, Paulo

    2013-11-01

    For patients with end-stage liver disease, commonly used indices of nutritional status (ie, body weight and body mass index) are often inflated because of fluid overload (ie, ascites and peripheral edema), and this results in an underdiagnosis of malnutrition. Because muscle is the largest protein reservoir in the body, an estimate of the muscle mass may be a more reliable and valid estimate of nutritional status. Therefore, we used pretransplant computed tomography data for 338 liver transplantation (LT) candidates to identify muscle and fat mass on the basis of a specific abdominal transverse section commonly used in body composition analyses, and we investigated the contribution of this measure to specific post-LT outcomes. We found that the majority of our patients (68%) could be defined as cachectic. For men, muscle mass predicted many important posttransplant outcomes, including intensive care unit (ICU) stay, total length of stay (LOS), and days of intubation. Muscle mass was a significant predictor of survival and also predicted disposition to home versus another facility. For women, muscle mass predicted ICU stay, total LOS, and days of intubation, but the effect was modest. Muscle mass did not predict survival or disposition for women. In conclusion, because pretransplant muscle mass is associated with many important postoperative outcomes, we discuss these findings in the context of possible pretransplant interventions for either improving or sustaining muscle mass before surgery. © 2013 American Association for the Study of Liver Diseases.

  9. Muscle Mass Predicts Outcomes Following Liver Transplantation

    PubMed Central

    DiMartini, Andrea; Cruz, Ruy J.; Dew, Mary Amanda; Myaskovsky, Larissa; Goodpaster, Bret; Fox, Kristen; Kim, Kevin H.; Fontes, Paulo

    2015-01-01

    Background and aims For patients with end-stage liver disease commonly used indices of nutritional status (i.e. body weight and BMI) are often inflated due to fluid overload (i.e. ascites, peripheral edema) resulting in an underdiagnosis of malnutrition. As muscle is the largest protein reservoir in the body, an estimate of muscle mass may be a more reliable and valid estimate of nutritional status. Methods Therefore, we used pre-transplant computerized tomography data of 338 liver transplant (LTX) candidates to identify muscle and fat mass based on a specific abdominal transverse section commonly used in body composition analyses and investigated the contribution of this measure to specific post-LTX outcomes. Results We found the majority, 68%, of our patients could be defined as cachetic. For men muscle mass predicted many important post-transplant outcomes including intensive care unit (ICU) and total length of stay and days of intubation. Muscle mass was a significant predictor of survival and also predicted disposition to home vs another facility. For women muscle mass predicted lengths of ICU and total stay and days of intubation but the effect was modest. Muscle mass did not predict survival or disposition for women. Conclusions As pre-transplant muscle mass was associated with many important post-operative outcomes we discuss these findings in the context of possible pre-transplant interventions to either improve or sustain muscle mass before surgery. PMID:23960026

  10. [Liver involvement in hemophagocytic syndrome].

    PubMed

    Larroche, Claire; Ziol, Marianne; Zidi, Sémia; Dhote, Robin; Roulot, Dominique

    2007-11-01

    Hemophagocytic syndrome (HPS), whether familial or acquired, is a clinico-pathological entity, characterized by uncontrolled hyper-inflammation, leading sometimes to a lifethreatening condition. Liver dysfunction is central in HPS: hepatomegaly is discovered in half cases, liver enzyme elevation and/or cholestasis are very frequent, cholestasis is a prognostic factor, and liver biopsy is often necessary to confirm HPS and to diagnose the underlying disorders in secondary HPS. The spectrum is large from acquired SAM than can be cured with the treatment of his trigger, to genetic cases only cured by stem cell transplantation.

  11. Liver involvement in hereditary hemorrhagic telangiectasia (HHT).

    PubMed

    Garcia-Tsao, Guadalupe

    2007-03-01

    Liver involvement in hereditary hemorrhagic telangiectasia (HHT) consists of extensive intrahepatic vascular malformations associated with blood shunting (arteriovenous, arterioportal and/or portovenous). It is a rare disorder that nevertheless can result in significant systemic and hepatobiliary abnormalities. Although hepatic vascular malformations are present in a majority of patients with HHT, symptoms occur in a only a minority with a clear predominance for the female gender. Symptoms from liver vascular malformations are often misdiagnosed and this can lead to potentially harmful interventions. In this review article, clinical findings of liver involvement in HHT and their pathophysiology are discussed as well as diagnostic methodologies, therapies used and their outcome. Data presented is based on a review of the literature performed in October 2006 using the following MEDLINE search terms: (hereditary hemorrhagic telangiectasia [ALL] OR Rendu-Osler-Weber [ALL]) AND (liver OR hepatic [ALL]). Papers were considered if they were published in English and if they included specific cases that were sufficiently described.

  12. Common Variable Immunodeficiency and Liver Involvement.

    PubMed

    Song, Junmin; Lleo, Ana; Yang, Guo Xiang; Zhang, Weici; Bowlus, Christopher L; Eric Gershwin, M; Leung, Patrick S C

    2017-08-07

    Common variable immunodeficiency (CVID) is a primary B-cell immunodeficiency disorder, characterized by remarkable hypogammaglobulinemia. The disease can develop at any age without gender predominance. The prevalence of CVID varies widely worldwide. The underlying causes of CVID remain largely unknown; primary B-cell dysfunctions, defects in T cells and antigen-presenting cells are involved. Although some monogenetic defects have been identified in some CVID patients, it is likely that CVID is polygenic. Patients with CVID develop recurrent and chronic infections (e.g., bacterial infections of the respiratory or gastrointestinal tract), autoimmune diseases, lymphoproliferation, malignancies, and granulomatous lesions. Interestingly, autoimmunity can be the only clinical manifestation of CVID at the time of diagnosis and may even develop prior to hypogammaglobulinemia. The diagnosis of CVID is largely based on the criteria established by European Society for Immunodeficiencies and Pan-American Group for Immunodeficiency (ESID/PAGID) and with some recent modifications. The disease can affect multiple organs, including the liver. Clinical features of CVID patients with liver involvement include abnormal liver biochemistries, primarily elevation of alkaline phosphatase (ALP), nodular regenerative hyperplasia (NRH), or liver cirrhosis and its complications. Replacement therapy with immunoglobulin (Ig) and anti-infection therapy are the primary treatment regimen for CVID patients. No specific therapy for liver involvement of CVID is currently available, and liver transplantation is an option only in select cases. The prognosis of CVID varies widely. Further understanding in the etiology and pathophysiology will facilitate early diagnosis and treatments to improve prognosis.

  13. Prevertebral muscle involvement in nasopharyngeal carcinoma

    SciTech Connect

    Feng, A.-C.; Wu, M.-C.; Tsai, Stella Y.C. . E-mail: afeng@mail.kfcc.org.tw; Chan, K.-Y.; Cheng, Skye H.; Wang, Angel; Chen, S.-S.; Jian, James J.; Terng, S.-D.; Huang, Andrew T.

    2006-07-15

    Purpose: The purpose of this study is to evaluate the prevalence and prognostic significance of prevertebral muscle involvement in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Between July 1990 and December 2001, 521 newly diagnosed patients with NPC treated at Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were examined with magnetic resonance imaging (MRI) for evidence of prevertebral muscle involvement before treatment. Patients were staged according to the 1997 American Joint Committee on Cancer staging classification of NPC based on the physical exams and MRI findings. All patients received radiotherapy with or without chemotherapy. The association between clinical prevertebral muscle involvement and posttreatment outcomes (overall survival, locoregional recurrence, and distant metastasis) were evaluated using Cox regression model to adjust for other prognostic factors. Results: Of 521 patients treated at KF-SYSCC, 181 (35%) patients were found to have prevertebral muscle involvement, one-third in those with Stage II/III tumors and two-thirds in those with Stage IV tumor. In multivariate analysis accounting for all previously known prognostic factors, prevertebral muscle invasion was associated with an increased risk for any recurrence (adjusted relative risk, 2.01; p < 0.001), locoregional recurrence (adjusted relative risk, 2.69; p < 0.001), and distant metastasis (adjusted relative risk, 2.25; p < 0.001), and with a borderline significant increased risk for overall survival (adjusted relative risk, 1.44; p = 0.10). Conclusions: Prevertebral muscle involvement is an independent prognostic factor for NPC recurrence.

  14. Lower Muscle Endurance in Patients with Alcoholic Liver Disease

    ERIC Educational Resources Information Center

    Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

    2012-01-01

    Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

  15. Lower Muscle Endurance in Patients with Alcoholic Liver Disease

    ERIC Educational Resources Information Center

    Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

    2012-01-01

    Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

  16. A comparative study of aldolase from human muscle and liver

    PubMed Central

    Eagles, Peter A. M.; Iqbal, Muzaffar

    1973-01-01

    Aldolase was purified from human skeletal muscle and human liver by techniques capable of processing large quantities (10–20kg) of tissue. The methods used also proved convenient for isolating aldolase on a large scale from other mammalian and avian sources. Aldolase from both human liver and muscle was crystallized; each gave two crystalline forms, depending on the conditions of crystallization. X-ray studies on the muscle aldolase crystals suggest a close structural similarity between human and rabbit muscle aldolase. Aldolases from human muscle and liver have similar pH optima and pH stability but their stability to heat treatment differs. The effect of heat on the enzymes may therefore provide an easy means of distinguishing them. The kinetic constants Km and kcat. for these aldolases are similar to other mammalian aldolases. Amino acid analyses and tryptic peptide `mapping' show that the primary structures of the two aldolases differ greatly. ImagesPLATE 1PLATE 2 PMID:4733235

  17. The Influence of Skeletal Muscle on the Regulation of Liver:Body Mass and Liver Regeneration

    PubMed Central

    Huang, Jiansheng; Glauber, Martin; Qiu, Zhaohua; Gazit, Vered; Dietzen, Dennis J.; Rudnick, David A.

    2012-01-01

    The relationship between liver and body mass is exemplified by the precision with which the liver:body mass ratio is restored after partial hepatic resection. Nevertheless, the compartments, against which liver mass is so exquisitely regulated, currently remain undefined. In the studies reported here, we investigated the role of skeletal muscle mass in the regulation of liver:body mass ratio and liver regeneration via the analysis of myostatin-null mice, in which skeletal muscle is hypertrophied. The results showed that liver mass is comparable and liver:body mass significantly diminished in the null animals compared to age-, sex-, and strain-matched controls. In association with these findings, basal hepatic Akt signaling is decreased, and the expression of the target genes of the constitutive androstane receptor and the integrin-linked kinase are dysregulated in the myostatin-null mice. In addition, the baseline expression levels of the regulators of the G1-S phase cell cycle progression in liver are suppressed in the null mice. The initiation of liver regeneration is not impaired in the null animals, although it progresses toward the lower liver:body mass set point. The data show that skeletal muscle is not the body component against which liver mass is positively regulated, and thus they demonstrate a previously unrecognized systemic compartmental specificity for the regulation of liver:body mass ratio. PMID:22155110

  18. Locating the source of hyperglycemia: Liver versus muscle

    PubMed Central

    YU, Haoyong; ZHOU, Dequan; JIA, Weiping; GUO, ZengKui

    2014-01-01

    Background Glucose homeostasis relies on insulin to suppress hepatic glucose production and to stimulate glucose uptake by peripheral tissues (primarily skeletal muscle) during and after a meal or glucose load. Glucose metabolism impairments in the liver and/or muscle attenuate these insulin actions, causing hyperglycemia. Thus, identifying the loci of the impairments can improve the understanding of hyperglycemia and enable organtargeted interventions. Methods Studies were performed to identify such loci using modified oral glucose tolerance test (OGTT) techniques in individuals with type 2 diabetes (T2D) and overweight/obese individuals. Results Individuals with severe T2D were found to have significantly impaired glucose metabolism in both the liver and muscle. In contrast, impairments in glucose metabolism in individuals with non-severe T2D were predominantly localized in the liver or muscle, but not both. Similarly, milder impairments in overweight or obese individuals were clearly localized in either the liver or muscle, but not both. All these impairments are quantifiable. Conclusion Impairments in glucose metabolism in the liver and muscle can be differentiated and quantified in a clinical setting. PMID:22074132

  19. Chronic exercise increases insulin binding in muscles but not liver

    SciTech Connect

    Bonen, A.; Clune, P.A.; Tan, M.H.

    1986-08-01

    It has been postulated that the improved glucose tolerance provoked by chronic exercise is primarily attributable to increased insulin binding in skeletal muscle. Therefore, the authors investigated the effects of progressively increased training (6 wk) on insulin binding by five hindlimb skeletal muscles and in liver. In the trained animals serum insulin levels at rest were lower either in a fed or fasted state and after an oral glucose tolerance test. Twenty-four hours after the last exercise bout sections of the liver, soleus (S), plantaris (P), extensor digitorum longus (EDL), and red (RG) and white gastrocnemius (WG) muscles were pooled from four to six rats. Insulin binding to plasma membranes increased in S, P, and EDL but not in WG or in liver. There were insulin binding differences among muscles. Comparison of rank orders of insulin binding data with published glucose transport data for the same muscles revealed that these parameters do not correspond well. In conclusion, insulin binding to muscle is shown to be heterogeneous and training can increase insulin binding to selected muscles but not liver.

  20. Leg muscle involvement in facioscapulohumeral muscular dystrophy assessed by MRI.

    PubMed

    Olsen, David B; Gideon, Peter; Jeppesen, Tina Dysgaard; Vissing, John

    2006-11-01

    Using MRI, we evaluated the degree of involvement of muscles in the lower extremities of 18 unselected patients with facioscapulohumeral muscular dystrophy (FSHD). Findings were correlated with fragment size of the mutated gene, age, disease duration and muscle power. Most affected muscles were the hamstrings followed by the tibialis anterior and the medial gastrocnemius. The vastus-, gluteal- and peroneal muscles were the most unaffected, and the psoas muscle did not show evidence of involvement in any of the investigated subjects. Asymmetric involvement was evident in 15% of the investigated muscles on MRI and 6% on manual muscle strength testing. MRI findings in muscle tended to correlate with disease duration (r = 0.49; p < 0.05), but not with gene fragment size or age. MRI disclosed involvement of muscles performing hip flexion and ankle dorsal flexion that could not be detected by manual muscle strength testing. Otherwise, there was a close correlation (approximately r = 0.75; p < 0.0001) between muscle strength and MRI severity score for other muscle groups. The present study shows that MRI may disclose muscle involvement in FSHD that is not apparent on manual muscle testing, and suggests that MRI of muscle may be an important assessment tool in clinical trials involving patients with FSHD.

  1. Sex-specific divergence of antioxidant pathways in fetal brain, liver, and skeletal muscles.

    PubMed

    Al-Gubory, Kaïs H; Garrel, Catherine

    2016-01-01

    The sex-specific divergence of antioxidant pathways in fetal organs of opposite-sex twin is unknown and remains urgently in need of investigation. Such study faces many challenges, mainly the ethical impossibility of obtaining human fetal organs. Opposite-sex sheep twins represent a unique model for studying a sex dimorphism for antioxidant systems. The activity of total superoxide dismutase (SOD), SOD1, SOD2, glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT), the content of total glutathione, reduced glutathione (GSH), and oxidized glutathione (GSSG) were measured in brain, lung, liver, kidney, and skeletal muscles of female and male fetuses collected from sheep twin pregnancies at day 65 of gestation. Lipid peroxidation was assessed by measuring melondialdehyde (MDA) tissue content. Male brain has greater total SOD and SOD1 activities than female brain. Female liver has greater SOD2 activity than male liver. Male liver has greater GR activity than female liver. Male liver has higher total GSH and GSSG content than female liver. Male skeletal muscles have higher total GSH, GSH, and GSSG content than female skeletal muscles. Female brain and liver have higher MDA content than male brain and liver. This is the first report of a sex dimorphism for fetal organ antioxidative pathways. Brain, liver, and skeletal muscles of male and female fetuses display distinct antioxidant pathways. Such sexually dimorphic responses to early life oxidative stress might be involved in the sex-related difference in fetal development that may have a long-term effect on offspring. Our study urges researchers to take into consideration the importance of sex as a biologic variable in their investigations.

  2. Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus).

    PubMed

    Fedorov, Vadim B; Goropashnaya, Anna V; Tøien, Oivind; Stewart, Nathan C; Gracey, Andrew Y; Chang, Celia; Qin, Shizhen; Pertea, Geo; Quackenbush, John; Showe, Louise C; Showe, Michael K; Boyer, Bert B; Barnes, Brian M

    2009-04-10

    We conducted a large-scale gene expression screen using the 3,200 cDNA probe microarray developed specifically for Ursus americanus to detect expression differences in liver and skeletal muscle that occur during winter hibernation compared with animals sampled during summer. The expression of 12 genes, including RNA binding protein motif 3 (Rbm3), that are mostly involved in protein biosynthesis, was induced during hibernation in both liver and muscle. The Gene Ontology and Gene Set Enrichment analysis consistently showed a highly significant enrichment of the protein biosynthesis category by overexpressed genes in both liver and skeletal muscle during hibernation. Coordinated induction in transcriptional level of genes involved in protein biosynthesis is a distinctive feature of the transcriptome in hibernating black bears. This finding implies induction of translation and suggests an adaptive mechanism that contributes to a unique ability to reduce muscle atrophy over prolonged periods of immobility during hibernation. Comparing expression profiles in bears to small mammalian hibernators shows a general trend during hibernation of transcriptional changes that include induction of genes involved in lipid metabolism and carbohydrate synthesis as well as depression of genes involved in the urea cycle and detoxification function in liver.

  3. [Multiple primary malignant tumors involving the liver].

    PubMed

    Tiszlavicz, L

    1991-11-17

    In the autopsy material of the Department of Pathology of Albert Szent-Györgyi Medical University 167 primary liver cancers were observed in 30 years, from which 13 patients (7.8%) had also other primary malignancies. The tumour-associations were mainly synchronously, there was strong male predominance. In 9 cases the hepatocellular carcinoma originated in cirrhotic liver. The most frequent extrahepatic tumours were found in the lungs (5 cases), smoking was among the anamnestic data.

  4. Muscle involvement in juvenile idiopathic arthritis.

    PubMed

    Lindehammar, H; Lindvall, B

    2004-12-01

    An observational study of changes in muscle structure and the relation to muscle strength in juvenile idiopathic arthritis (JIA). Fifteen children and teenagers (eight girls and seven boys) with JIA, aged 9-19 yr (mean age 16.1), were studied. Muscle biopsies were obtained from the anterior tibial muscle and were examined using histopathological and immunohistochemical methods. Muscle fibre types were classified and fibre areas measured. As markers of inflammation, the major histocompatibility complex (MHC) class I and class II and the membrane attack complex (MAC) were analysed. Results were compared with biopsies from the gastrocnemius muscle in 33 young (19-23 yr) healthy controls. Isometric and isokinetic muscle strengths were measured in ankle dorsiflexion. Strength was compared with reference values for healthy age-matched controls. Nerve conduction velocities were recorded in the peroneal and sural nerves. Four of the 15 muscle biopsies were morphologically normal. Eleven biopsies showed minor unspecific changes. Two of these also showed minor signs of inflammation. MHC class II expression was found in 4/15 patients, which was significantly more than in the healthy controls (P = 0.0143). The expression of MHC class I and MAC did not differ from that in the controls. The mean area of type I fibres was lower than that of type IIA fibres in 12/13 biopsies. Muscle strength was significantly reduced in the patient group. There was a significant positive correlation between muscle fibre area and muscle strength. Nerve conduction studies were normal in all cases. Changes in leg muscle biopsies appear to be common in children and teenagers with JIA. The presence of inflammatory cells in the muscle and expression of MHC class II on muscle fibres may be a sign of inflammatory myopathy. There are no findings of type II muscle fibre hypotrophy or neuropathy, as in adults with RA.

  5. Schistosomiasis Japonicum Involving the Liver and Colon

    DTIC Science & Technology

    2007-02-01

    presentation, typical imaging findings, and treatment of Schistosomiasis. Schistosomiasis is a chronic infection caused by parasitic trematode worms that...ova are subsequently deposited within the liver, gastrointestinal tract, and genitourinary tract and a granulomatous and fibrotic reaction ensues...potentially result in permanent gastrointestinal and urinary system damage if not appropriately treated. History A 51-year-old female

  6. Liver involvement in children with Familial Mediterranean fever.

    PubMed

    Unal, Fatih; Cakir, Murat; Baran, Masallah; Arıkan, Cigdem; Yuksekkaya, Hasan Ali; Aydoğdu, Sema

    2012-08-01

    Familial Mediterranean fever is characterised by recurrent, febrile, inflammatory attacks of the serosal membranes. Prolonged inflammatory response is triggered secondary to cytokine stimulation due to reduced activity of pyrin. Inflammatory cytokines play major role in the pathogenesis of acute liver injury; and chronic, recurrent cytokine production may cause chronic hepatitis/cirrhosis. We aimed to analyse liver involvement in children with Familial Mediterranean fever. The study included 58 patients with Familial Mediterranean fever. Patients with liver involvement were examined in detail. Liver involvement was seen in 11 of 58 patients (18.9%). Two patients (3.4%) had abnormal liver enzymes during the diagnostic evaluation, whilst 9 patients (15.5%) were admitted with the features of liver diseases, and had final diagnosis of Familial Mediterranean fever (2 had Budd-Chiari syndrome, 5 had chronic hepatitis/cirrhosis, 2 had acute hepatitis). None of the demographic factors or laboratory findings was different between the patients with or without liver involvement M694V allele was more common in patients with liver involvement but did not reach significant difference (50% vs. 33.6%, p=0.21). All the patients showed clinical and laboratory improvement after colchicine. Paediatric hepatologists must keep Familial Mediterranean fever in mind in the patients with cryptogenic hepatitis/cirrhosis especially in regions where hereditary inflammatory diseases are common. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  7. Iliopsoas muscle hematoma secondary to alcoholic liver cirrhosis.

    PubMed

    Yamashita, Suguru; Tanaka, Nobutaka; Nomura, Yukihiro; Miyahara, Takuya; Furuya, Takatoshi

    2012-09-01

    Iliopsoas muscle hematoma in a patient with alcoholic liver cirrhosis is rarely seen, however it has a high mortality. Thus we should cautiously make a diagnosis and treatment. This is the case of a 60-year-old male. He had a 15-year history of alcoholic liver disease and emphysema. He presented with low back pain after a fall that had happened 2 months before. Due to persistent back pain, he went to see a local physician who, after detailed examination, suspected rupture of bilateral common iliac artery aneurysms and transferred the patient to our hospital. The same presumptive diagnosis was made, and on this basis, an aortic bifemoral Y-graft was implanted. He developed aspiration pneumonia and hepatic and renal dysfunction postoperatively, which led to multiple organ failure and subsequent in-hospital death on postoperative day 62. This was believed to be a case of iliopsoas muscle hematoma developed in a patient with liver cirrhosis, and considering it was a case with poor surgical risk, a conservative treatment option such as transcatheter arterial embolization should also have been considered. Although iliopsoas muscle hematoma with alcoholic liver cirrhosis is rare, an appropriate treatment plan should be determined on a case-by-case basis despite its poor prognosis.

  8. Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

    PubMed Central

    Stapleton, David I.; Lau, Xianzhong; Flores, Marcelo; Trieu, Jennifer; Gehrig, Stefan M.; Chee, Annabel; Naim, Timur; Lynch, Gordon S.; Koopman, René

    2014-01-01

    Background Duchenne muscular dystrophy (DMD) is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd) gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD) exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice. Results Dystrophic mdx mice had increased skeletal muscle glycogen (79%, (P<0.01)). Skeletal muscle glycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (P<0.0001). Glycogen synthase activity was 12% higher (P<0.05) but glycogen branching enzyme activity was 70% lower (P<0.01) in mdx compared with wild-type mice. The rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 62% lower activity (P<0.01) in mdx mice resulting from a 24% reduction in PKA activity (P<0.01). In mdx mice glycogen debranching enzyme expression was 50% higher (P<0.001) together with starch-binding domain protein 1 (219% higher; P<0.01). In addition, mdx mice were glucose intolerant (P<0.01) and had 30% less liver glycogen (P<0.05) compared with control mice. Subsequent analysis of the enzymes dysregulated in skeletal muscle glycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; P<0.05) as a possible cause of this phenotype. Conclusion We identified that mdx mice were glucose intolerant, and had increased skeletal muscle glycogen but reduced amounts of liver glycogen. PMID:24626262

  9. Myositis ossificans circumscripta involving bilateral masticatory muscles.

    PubMed

    Godhi, Suhas S; Singh, Anurag; Kukreja, Pankaj; Singh, Vishal

    2011-11-01

    Myositis ossificans (MO), as its name implies, is ossification and bone formation within a muscle. Pathogenesis is not all clear, but trauma is universally recognized as a trigger event. Myositis ossificans can be divided into 2 classifications: MO progressiva and MO traumatica. When it affects the muscles of mastication, it causes severe trismus. This rare disorder and its limited treatment options can potentially have debilitating effects to the patient's normal oral functioning and health. A computed tomographic scan and panoramic radiographs are essential diagnostic aids for evaluating conditions such as MO. Myositis ossificans can be one of the causes of extra-articular temporomandibular joint ankylosis. Surgical excision of the ossification is the main treatment modality. This is a case report of a patient who developed MO of the muscles of mastication.

  10. [Multiple primary malignant tumors involving the liver].

    PubMed

    Tiszlavicz, L; Tasnádi, T

    1993-01-31

    In the Department of Pathology of the Albert Szent-Györgyi Medical University in Szeged during the last 30 years 1770 (19.4% of the cancers) primary malignant lung tumours were observed in autopsy material, from which 86 patients (4.9%) had other malignancies as well. In 81 cases other extrapulmonary and in 5 cases other primary lung tumours were observed. The male predominance in these cases was significant. All of the patients were heavy smokers. Amongst these synchronous tumour-associations the most frequent extrapulmonary tumours arose in the urogenital tract, in the head and neck, relatively frequently also in the breast, liver, stomach, intestine and thyroid. These cases caused diagnostic dilemmas both for the clinician and even for the pathologist. Several signs help to distinguish a new primary tumour from a metastasis. Multiplicity itself does not mean poorer prognosis. Each cancer should possibly receive adequate treatment.

  11. Involvement of liver in diabetes mellitus: herbal remedies.

    PubMed

    Thent, Z C; Das, S

    2014-01-01

    Liver disease is considered as one of the major complications in oxidative stress disorders like diabetes mellitus (DM). DM presents with deterioration in carbohydrate metabolism which is characterized with chronic hyperglycemia. The organ which involves in glucose or carbohydrate metabolism and is most likely to be affected is the liver. Deterioration in liver architecture and metabolism in DM, are considered as common findings. In the present review both biochemical and histological changes occurring in diabetic liver are conferred in detail. To counteract the oxidative stress disorders and its untoward complications, antioxidant or herbs have emerged as alternative medicine. The present review focuses on several herbs with antioxidant properties towards diabetic liver disease such as Liquorice, Pelargonium gravenolens, Momordica charantia, Propolis from bee hives, Dihar, Curcuma Longa, Tinospora cordifolia, Kangen-karyu, Parsley, Chard, Green tea Catechins and Piper sarmentosum (P.s). The herbs or the compounds present in herbs have potential to improve the liver metabolism and maintain the integrity of liver tissue in DM. The review also opens the door for effective use of herbal products for complications involved in the diabetic liver disease.

  12. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  13. Liver, but Not Muscle, Has an Entrainable Metabolic Memory

    PubMed Central

    Mulligan, Kimberly X.; Lundblad, Tammy M.; Williams, Phillip E.; McGuinness, Owen P.

    2014-01-01

    Hyperglycemia in the hospitalized setting is common, especially in patients that receive nutritional support either continuously or intermittently. As the liver and muscle are the major sites of glucose disposal, we hypothesized their metabolic adaptations are sensitive to the pattern of nutrient delivery. Chronically catheterized, well-controlled depancreatized dogs were placed on one of three isocaloric diets: regular chow diet once daily (Chow) or a simple nutrient diet (ND) that was given either once daily (ND-4) or infused continuously (ND-C). Intraportal insulin was infused to maintain euglycemia. After 5 days net hepatic (NHGU) and muscle (MGU) glucose uptake and oxidation were assessed at euglycemia (120 mg/dl) and hyperglycemia (200 mg/dl) in the presence of basal insulin. While hyperglycemia increased both NHGU and MGU in Chow, NHGU was amplified in both groups receiving ND. The increase was associated with enhanced activation of glycogen synthase, glucose oxidation and suppression of pyruvate dehydrogenase kinase-4 (PDK-4). Accelerated glucose-dependent muscle glucose uptake was only evident with ND-C. This was associated with a decrease in PDK-4 expression and an increase in AMP-activated protein kinase (AMPK) phosphorylation. Interestingly, ND-C markedly increased hepatic FGF-21 expression. Thus, augmentation of carbohydrate disposal in the liver, as opposed to the muscle, is not dependent on the pattern of nutrient delivery. PMID:24465939

  14. Involvement of connexin43 in acetaminophen-induced liver injury

    PubMed Central

    Maes, Michaël; McGill, Mitchell R.; da Silva, Tereza Cristina; Abels, Chloé; Lebofsky, Margitta; Maria Monteiro de Araújo, Cintia; Tiburcio, Taynã; Veloso Alves Pereira, Isabel; Willebrords, Joost; Crespo Yanguas, Sara; Farhood, Anwar; Beschin, Alain; Van Ginderachter, Jo A.; Zaidan Dagli, Maria Lucia; Jaeschke, Hartmut; Cogliati, Bruno; Vinken, Mathieu

    2017-01-01

    Background and aims Being goalkeepers of liver homeostasis, gap junctions are also involved in hepatotoxicity. However, their role in this process is ambiguous, as gap junctions can act as both targets and effectors of liver toxicity. This particularly holds true for drug-induced liver insults. In the present study, the involvement of connexin 26, connexin32 and connexin43, the building blocks of liver gap junctions, was investigated in acetaminophen-induced hepatotoxicity. Methods C57BL/6 mice were overdosed with 300 mg/kg body weight acetaminophen followed by analysis of the expression and localization of connexins as well as monitoring of hepatic gap junction functionality. Furthermore, acetaminophen-induced liver injury was compared between mice genetically deficient in connexin43 and wild type littermates. Evaluation of the toxicological response was based on a set of clinically relevant parameters, including protein adduct formation, measurement of alanine aminotransferase activity, cytokines and glutathione. Results It was found that gap junction communication deteriorates upon acetaminophen intoxication in wild type mice, which is associated with a switch in mRNA and protein production from connexin32 and connexin26 to connexin43. The upregulation of connexin43 expression is due, at least in part, to de novo production by hepatocytes. Connexin43-deficient animals tended to show increased liver cell death, inflammation and oxidative stress in comparison with wild type counterparts. Conclusion These results suggest that hepatic connexin43-based signaling may protect against acetaminophen-induced liver toxicity. PMID:26912412

  15. Skeletal muscle and liver oxysterols during fasting and alcohol exposure.

    PubMed

    Adachi, Junko; Kudo, Risa; Asano, Migiwa; Ueno, Yasuhiro; Hunter, Ross; Rajendram, Rajkumar; Martin, Colin; Preedy, Victor R

    2006-01-01

    Oxysterols are cytotoxic agents that have a range of cellular actions, including impairment of albumin synthesis, cell differentiation, and induction of apoptosis. Their regulations by nutritional factors are poorly described. Our objective was to test the hypothesis that the imposition of food withdrawal and alcohol exposure increases tissue oxysterol concentrations. We measured the concentrations of the oxysterols 7alpha-hydroxycholest-5-en-3beta-ol (7alpha-OH), 7beta-hydroxycholest-5-en-3beta-ol (7beta-OH), and 3beta-hydroxycholest-5-en-7-one (7-keto) in liver and skeletal muscle of fed and fasted (food withdrawal for 1 and 2 days) male Wistar rats. Both oxidative (type I; soleus) and glycolytic (type II; plantaris) muscles were analyzed. We also investigated the effects of a nutritional perturbant induced by a short-term bolus of ethanol (75 mmol/kg weight IP administered 2.5 hours before sacrifice). The results showed that in response to fasting there were significant increases in 7alpha-OH, 7beta-OH, and 7-keto in liver and both type I and II skeletal muscle (P < .001 in all instances). For skeletal muscle, the increases were blunted or ameliorated after 2 days when compared with data from rats starved for 1 day. In contrast, the increases in liver after 1 day's fasting were relatively sustained at 2 days. Short-term ethanol increased 7alpha-OH, 7beta-OH, and 7-keto in type I muscle of fed animals only (P < .001 in all instances) with a significant interaction between fasting and alcohol (P < .001 in all instances). For the first time, we have shown that oxysterols can increase in muscle and liver in response to food withdrawal and in response to an immediately imposed nutritional perturbant (ie, alcohol). Increased oxysterols represent elevated oxidative stress and/or disturbances in their formation or clearance. Because of the reported cytotoxic properties of oxysterols, these data are important in understanding cellular pathology because episodic anorexia

  16. Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis.

    PubMed

    Simon, Neil G; Lee, Michael; Bae, Jong Seok; Mioshi, Eneida; Lin, Cindy S-Y; Pfluger, Casey M; Henderson, Robert D; Vucic, Steve; Swash, Michael; Burke, David; Kiernan, Matthew C

    2015-06-01

    It has been suggested that corticomotoneuronal drive to ankle dorsiflexors is greater than to ankle plantar flexor muscles, despite the finding that plantar flexors are no less active than TA during walking and standing. The present study was undertaken to determine whether there was differential involvement of distal lower limb muscles in amyotrophic lateral sclerosis (ALS), to elucidate pathophysiological mechanisms of selective muscle involvement. Prospective studies were undertaken in 52 ALS patients, including clinical assessment, disease staging (revised ALS functional rating scale), Medical Research Council sum score, and a scale of upper motor neurone (UMN) dysfunction. Motor unit number estimates (MUNE) and compound muscle action potentials (CMAP) from ankle dorsiflexors and plantar flexors were used to provide objective measures. A novel 'split leg index' was calculated as follows: SLI = CMAPDF ÷ CMAPPF. In ALS, there was significantly greater reduction of MUNE and CMAP amplitude recorded from plantar flexors when compared to dorsiflexors, suggesting preferential involvement of plantar flexor muscles, underpinning a 'split leg' appearance. The SLI correlated with clinical plantar flexor strength (R= -0.56, p < 0.001). In no patient did the SLI suggest preferential dorsiflexor involvement. In subgroup analyses, mean SLI was greatest in lower limb-onset ALS. In conclusion, the present study has established dissociated involvement of muscles acting around the ankle in ALS. We suggest this reflects underlying differences in cortical, descending or local spinal modulation of these muscles.

  17. Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1.

    PubMed

    Bai, Qingyun; Yan, Hongyu; Sheng, Yuchen; Jin, Yao; Shi, Liang; Ji, Lili; Wang, Zhengtao

    2017-05-01

    Acetaminophen (APAP)-induced acute liver injury has already been well studied. However, whether long-term administration of APAP will cause liver fibrosis is still not very clear. This study aims to investigate the liver fibrosis in mice induced by long-term APAP treatment and the involvement of early growth response 1 (Egr-1). C57BL/6 mice were orally given with APAP (200, 300mg/kg) for 2, 6 or 10 weeks, respectively. Liver hydroxyproline content, collagen deposition and inflammatory cells infiltration were increased in mice treated with APAP (200, 300mg/kg) for 6 or 10 weeks. Liver mRNA expression of collagen (COL)1a1, Col3a1, transforming growth factor-β (TGF-β) and serum contents of COL1, COL3, TGF-β were all increased in APAP-treated mice. Liver expression of α-smooth muscle actin (α-SMA) and phosphorylated ERK1/2 and Smad2/3 were all increased in APAP-treated mice. Furthermore, increased liver mRNA expression of Egr-1 and its subsequent nuclear translocation were found in APAP-treated mice. Egr-1 knock-out mice were further applied. APAP-induced liver fibrosis was found to be more serious in Egr-1 knock-out mice. N-acetyl-p-benzoquinoneimine (NAPQI), the APAP hepatotoxic metabolite, increased cellular mRNA expression of α-SMA, Col1a1, Col3a1, TGF-β, induced ERK1/2 and Smad2/3 phosphorylation and Egr-1 nuclear translocation in hepatic stellate LX2 cells. In conclusion, long-term administration of APAP induced liver fibrosis in mice, and Egr-1 was critically involved in this process. This study points out a warning and reference for patients with long-term APAP ingestion in clinic. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Liver involvement in Langerhans' cell histiocytosis. Case report.

    PubMed

    Dina, Ion; Copaescu, Catalin; Herlea, Vlad; Wrba, Fritz; Iacobescu, Claudia

    2006-03-01

    Langerhans'cell histiocytosis (Histiocytosis X) is a rare disease of unknown cause characterized by oligoclonal proliferation of Langerhans cells. It occurs mostly in children and young adults and involves one or more body systems such as bone, hypothalamus, posterior pituitary gland, lymph nodes, liver or various soft tissues. The diagnosis is always made by a histological approach. We report a case of Langerhans'cell histiocytosis in a young patient with clinical signs of diabetes insipidus and hepatic involvement in whom the immunohistochemical analysis of the liver tissue led to the definitive diagnosis.

  19. Relationships between organochlorine concentrations in liver and muscle of otters

    SciTech Connect

    Mason, C.F. )

    1989-10-01

    The European otter (Lutra lutra) is now threatened or endangered over much of its European range. The decline, which has taken place mainly during the past three decades, has been attributed to the toxic effects of organochlorine residues, with emphasis being placed on dieldrin or PCBs. Few otters were analyzed for organochlorines during the main period of decline but there is not considerable interest in the species. Experiments with ranch mink (Mustela vison) have shown that reproductive failure occurs when PCB concentrations in thigh muscle approach 50 mg kg{sup {minus}1} lipid. Because otters are closely related and have similar habits this value is becoming widely used to interpret the potential significance of PCB concentrations determined in otters. Furthermore, although the mink data refer to concentrations in muscle, interpretations of concentrations in otters have frequently been based on analyses of livers. Because of the diverse sources of material in Europe, only limited tissues may be made available for analysis, while costs may also prohibit the analysis of several tissues from a single carcass. The relationship between concentrations of organochlorines in muscle and liver tissues in otters has not been determined. This is the purpose of the present communication.

  20. Colonic involvement in amebic liver abscess: does site matter?

    PubMed Central

    Goswami, Amitava; Dadhich, Sunil; Bhargava, Narendra

    2014-01-01

    Background Colonic involvement in amebic liver abscess (ALA) occurs in more than half of the patients. However no studies have found any association between the site of the colonic lesions and location of abscesses in the liver. Thus, the present study was designed to find the correlation between colonic involvement in solitary and multiple ALAs. Methods This is a case control study of 80 patients allocated in two groups, the first with solitary (controls) and the second with multiple ALAs (cases). Colonoscopy was performed in all patients enrolled in the study. Results Solitary ALA was seen in 70% of patients whereas multiple ALAs in 30%. Colonic involvement in the form of erythema, inflammation and ulceration was seen in 77.5% of cases of ALA. 71.4 % cases of solitary ALA had colonic lesions compared to 91.6% cases of multiple ALAs (P=0.02). Most of the patients with multiple ALAs had involvement of the transverse and right colon (75%). Involvement of right colon was present in all patients with colonic involvement. A significant involvement of the right and transverse colon was seen in cases of multiple compared to solitary ALA (P<0.0001). Conclusion Colonic involvement is present in more than two thirds of patients with ALA. When colonic involvement is present, right colon lesion is universally present. Colonic involvement may extend beyond hepatic flexure in patients with multiple amebic ALAs, either involving right hepatic lobe or both lobes. PMID:24733082

  1. Pseudomalignant myositis ossificans involving multiple masticatory muscles: Imaging evaluation

    PubMed Central

    Kamalapur, Muralidhar G; Patil, Pritam B; Joshi, Shyamsundar; Shastri, Dinesh

    2014-01-01

    Myositis ossificans is a rare cause of trismus. We present a case of pseudomalignant myositis ossificans involving medial pterygoid, lateral pterygoid, and temporalis muscles. Patient presented with gross limitation in mouth opening. There was no history of trauma. Computed tomography (CT) images revealed a bone density mass located in the region of medial and lateral pterygoid muscles on the right and temporalis muscle on the left. Magnetic resonance imaging (MRI) showed similar findings. Radiological diagnosis was pseudomalignant myositis ossificans. The masses were resected and histopathologic examination confirmed the above diagnosis. This report describes the characteristic CT and MRI features. The unique feature of this case is the absence of history of trauma with involvement of multiple masticatory muscles, which, to the best of our knowledge, has not been reported before. PMID:24851010

  2. Pseudomalignant myositis ossificans involving multiple masticatory muscles: Imaging evaluation.

    PubMed

    Kamalapur, Muralidhar G; Patil, Pritam B; Joshi, Shyamsundar; Shastri, Dinesh

    2014-01-01

    Myositis ossificans is a rare cause of trismus. We present a case of pseudomalignant myositis ossificans involving medial pterygoid, lateral pterygoid, and temporalis muscles. Patient presented with gross limitation in mouth opening. There was no history of trauma. Computed tomography (CT) images revealed a bone density mass located in the region of medial and lateral pterygoid muscles on the right and temporalis muscle on the left. Magnetic resonance imaging (MRI) showed similar findings. Radiological diagnosis was pseudomalignant myositis ossificans. The masses were resected and histopathologic examination confirmed the above diagnosis. This report describes the characteristic CT and MRI features. The unique feature of this case is the absence of history of trauma with involvement of multiple masticatory muscles, which, to the best of our knowledge, has not been reported before.

  3. Mercury concentrations in muscle and liver tissue of fish from marshes along the Magdalena River, Colombia.

    PubMed

    Alvarez, Santiago; Kolok, Alan S; Jimenez, Luz Fernanda; Granados, Carlos; Palacio, Jaime A

    2012-10-01

    The present research determined the total mercury concentrations in muscle and liver tissue in fish collected from the Magdalena River watershed. A total of 378 muscle samples and 102 liver samples were included in the analysis. The highest mean mercury level in muscle tissue was found in the noncarnivore, Pimelodus blochii. However, as a group, carnivores had significantly higher (p < 0.05) mercury levels in their muscle tissue than noncarnivores. A significant correlation (p < 0.05) was obtained between fish mass and mercury concentrations in muscle or liver in four species. No differences were observed in total mercury concentration based either on species or gender.

  4. Involvement of nitric oxide system in experimental muscle crush injury.

    PubMed Central

    Rubinstein, I; Abassi, Z; Coleman, R; Milman, F; Winaver, J; Better, O S

    1998-01-01

    Muscle crush injury is often complicated by hemodynamic shock, electrolyte disorders, and myoglobinuric renal failure. In this study, we examined the involvement of the nitric oxide (NO) system in the development of muscle damage in an experimental model of crush injury induced by exertion of standardized mechanical pressure on tibialis muscle of rat. The intact limb served as a control. Four days after injury, the crushed muscle was characterized by extreme capillary vasodilatation as demonstrated by histological morphometric analysis. These changes were accompanied by muscle hyperperfusion as evaluated by measurements of femoral blood flow (ultrasonic flowmetry) and capillary blood flow (laser-doppler flowmetry). Treatment with Nomega-nitro-L-arginine methyl ester, a NO synthase (NOS) inhibitor, largely decreased the hyperperfusion. Furthermore, the expression of the different NOS isoforms, assessed by reverse transcription-PCR and immunoreactive levels, determined by Western blot, revealed a remarkable induction of the inducible NOS in the crushed limb. Similarly, endothelial NOS mRNA increased gradually after the induction of muscle damage. In contrast, the major muscular NOS, i.e., neuronal isoform remained unchanged. In line with the alterations in the mRNA levels, Western blot analysis revealed parallel changes in the immunoreactive levels of the various NOS. These findings indicate that muscle crush is associated with activation of the NO system mainly due to enhancement of iNOS. This may contribute to NO-dependent extreme vasodilatation in the injured muscle and aggravate the hypovolemic shock after crush injury. PMID:9502774

  5. Effects of distraction on muscle length: mechanisms involved in sarcomerogenesis.

    PubMed

    Caiozzo, Vincent J; Utkan, Ali; Chou, Richard; Khalafi, Afshin; Chandra, Heena; Baker, Michael; Rourke, Bryan; Adams, Greg; Baldwin, Ken; Green, Stuart

    2002-10-01

    Although a great deal of interest has been given to understanding the mechanisms involved in regulating the radial growth that occurs because of resistance training, much less has been given to studying the longitudinal growth of skeletal muscle that occurs because of passive stretch. The current authors provide a brief overview of key issues relevant to the longitudinal growth of skeletal muscle that occurs during distraction osteogenesis. Specifically, five key issues are addressed: (1) the pattern of sarcomerogenesis during distraction; (2) sarcomerogenesis and altered expression of sarcomeric and nonsarcomeric genes; (3) the satellite cell hypothesis; (4) mitogenic factors; and (5) new approaches for studying the longitudinal growth of skeletal muscle. A discussion is provided that revolves around the concept of a negative feedback loop. One of the most interesting issues to be resolved in muscle biology is the role of satellite cells in regulating the growth of skeletal muscle. Currently, it is not known whether satellite cell activation is a prerequisite for the longitudinal growth of skeletal muscle. Gene chip analyses provide a paradoxical view, showing that distraction osteogenesis results in the upregulation of a gene, GADD45, involved with growth arrest and deoxyribonucleic acid destruction.

  6. Skeletal muscle imaging in facioscapulohumeral muscular dystrophy, pattern and asymmetry of individual muscle involvement.

    PubMed

    Rijken, N H M; van der Kooi, E L; Hendriks, J C M; van Asseldonk, R J G P; Padberg, G W; Geurts, A C H; van Engelen, B G M

    2014-12-01

    To better understand postural and movement disabilities, the pattern of total body muscle fat infiltration was analyzed in a large group of patients with facioscapulohumeral muscular dystrophy. Additionally, we studied whether residual D4Z4 repeat array length adjusted for age and gender could predict the degree of muscle involvement. Total body computed tomography scans of 70 patients were used to assess the degree of fat infiltration of 42 muscles from neck to ankle level on a semi-quantitative scale. Groups of muscles that highly correlated regarding fat infiltration were identified using factor analysis. Linear regression analysis was performed using muscle fat infiltration as the dependent variable and D4Z4 repeat length and age as independent variables. A pattern of muscle fat infiltration in facioscapulohumeral muscular dystrophy could be constructed. Trunk muscles were most frequently affected. Of these, back extensors were more frequently affected than previously reported. Asymmetry in muscle involvement was seen in 45% of the muscles that were infiltrated with fat. The right-sided upper extremity showed significantly higher scores for fat infiltration compared to the left side, which could not be explained by handedness. It was possible to explain 29% of the fat infiltration based on D4Z4 repeat length, corrected for age and gender. Based on our results we conclude that frequent involvement of fat infiltration in back extensors, in addition to the abdominal muscles, emphasizes the extent of trunk involvement, which may have a profound impact on postural control even in otherwise mildly affected patients.

  7. Diabetes mellitus and renal involvement in chronic viral liver disease.

    PubMed

    Iovanescu, V F; Streba, C T; Ionescu, M; Constantinescu, A F; Vere, C C; Rogoveanu, I; Moța, E

    2015-01-01

    Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013<0.05) and presence of hepatitis C virus were particularly correlated with the presence of diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with

  8. Delayed onset muscle soreness: Involvement of neurotrophic factors.

    PubMed

    Mizumura, Kazue; Taguchi, Toru

    2016-01-01

    Delayed-onset muscle soreness (DOMS) is quite a common consequence of unaccustomed strenuous exercise, especially exercise containing eccentric contraction (lengthening contraction, LC). Its typical sign is mechanical hyperalgesia (tenderness and movement related pain). Its cause has been commonly believed to be micro-damage of the muscle and subsequent inflammation. Here we present a brief historical overview of the damage-inflammation theory followed by a discussion of our new findings. Different from previous observations, we have observed mechanical hyperalgesia in rats 1-3 days after LC without any apparent microscopic damage of the muscle or signs of inflammation. With our model we have found that two pathways are involved in inducing mechanical hyperalgesia after LC: activation of the B2 bradykinin receptor-nerve growth factor (NGF) pathway and activation of the COX-2-glial cell line-derived neurotrophic factor (GDNF) pathway. These neurotrophic factors were produced by muscle fibers and/or satellite cells. This means that muscle fiber damage is not essential, although it is sufficient, for induction of DOMS, instead, NGF and GDNF produced by muscle fibers/satellite cells play crucial roles in DOMS.

  9. Enucleation of human erythroblasts involves non-muscle myosin IIB

    PubMed Central

    Ubukawa, Kumi; Guo, Yong-Mei; Takahashi, Masayuki; Hirokawa, Makoto; Michishita, Yoshihiro; Nara, Miho; Tagawa, Hiroyuki; Takahashi, Naoto; Komatsuda, Atsushi; Nunomura, Wataru; Takakuwa, Yuichi

    2012-01-01

    Mammalian erythroblasts undergo enucleation, a process thought to be similar to cytokinesis. Although an assemblage of actin, non-muscle myosin II, and several other proteins is crucial for proper cytokinesis, the role of non-muscle myosin II in enucleation remains unclear. In this study, we investigated the effect of various cell-division inhibitors on cytokinesis and enucleation. For this purpose, we used human colony-forming unit-erythroid (CFU-E) and mature erythroblasts generated from purified CD34+ cells as target cells for cytokinesis and enucleation assay, respectively. Here we show that the inhibition of myosin by blebbistatin, an inhibitor of non-muscle myosin II ATPase, blocks both cell division and enucleation, which suggests that non-muscle myosin II plays an essential role not only in cytokinesis but also in enucleation. When the function of non-muscle myosin heavy chain (NMHC) IIA or IIB was inhibited by an exogenous expression of myosin rod fragment, myosin IIA or IIB, each rod fragment blocked the proliferation of CFU-E but only the rod fragment for IIB inhibited the enucleation of mature erythroblasts. These data indicate that NMHC IIB among the isoforms is involved in the enucleation of human erythroblasts. PMID:22049517

  10. Liver and muscle metabolic changes induced by dietary energy content and genetic selection in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Kolditz, C; Borthaire, M; Richard, N; Corraze, G; Panserat, S; Vachot, C; Lefèvre, F; Médale, F

    2008-04-01

    We combined genetic selection and dietary treatment to produce a model to study metabolic pathways involved in genetic and nutritional control of fat deposition in fish muscle. Two experimental lines of rainbow trout, selected for a lean (L) or fat (F) muscle, were fed with diets containing either 10 or 23% lipids from the first feeding, up to 6 mo. At the end of the feeding trial, trout were distinguished by very different muscle fat content (from 4.2 to 10% wet weight), and line x diet interactions were observed for parameters related to fat storage. We analyzed the activity and gene expression of key enzymes involved in lipid metabolism (fatty acid synthase, hydroxyacyl-CoA dehydrogenase, carnitine palmitoyltransferase 1 isoforms, and peroxisome proliferator-activated receptor alpha) and glycolysis (hexokinase 1 and pyruvate kinase) as well as energy production (isocitrate dehydrogenase, citrate synthase, and cytochrome oxidase) in the liver and the white muscle of rainbow trout. The lipid-rich diet repressed the activity of the lipogenic enzymes and stimulated enzymes involved in fatty acid oxidation and glycolysis in liver but had little effect on muscle enzymes assessed in this study. Regarding the selection effect, enzyme activity and expression suggest that compared with the L line, the F line presented reduced hepatic fatty acid oxidation as well as reduced mitochondrial oxidative capacities and enhanced glucose utilization in both liver and muscle. Very few line x diet interactions were found, suggesting that the two factors (i.e., dietary energy content and selection) used in this study to modify muscle lipid content exerted some additive but mostly independent effects on these metabolic actors.

  11. Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse.

    PubMed

    Kelly, Daniel M; Akhtar, Samia; Sellers, Donna J; Muraleedharan, Vakkat; Channer, Kevin S; Jones, T Hugh

    2016-11-01

    Testosterone deficiency is commonly associated with obesity, metabolic syndrome, type 2 diabetes and their clinical consequences-hepatic steatosis and atherosclerosis. The testicular feminised mouse (non-functional androgen receptor and low testosterone) develops fatty liver and aortic lipid streaks on a high-fat diet, whereas androgen-replete XY littermate controls do not. Testosterone treatment ameliorates these effects, although the underlying mechanisms remain unknown. We compared the influence of testosterone on the expression of regulatory targets of glucose, cholesterol and lipid metabolism in muscle, liver, abdominal subcutaneous and visceral adipose tissue. Testicular feminised mice displayed significantly reduced GLUT4 in muscle and glycolytic enzymes in muscle, liver and abdominal subcutaneous but not visceral adipose tissue. Lipoprotein lipase required for fatty acid uptake was only reduced in subcutaneous adipose tissue; enzymes of fatty acid synthesis were increased in liver and subcutaneous tissue. Stearoyl-CoA desaturase-1 that catalyses oleic acid synthesis and is associated with insulin resistance was increased in visceral adipose tissue and cholesterol efflux components (ABCA1, apoE) were decreased in subcutaneous and liver tissue. Master regulator nuclear receptors involved in metabolism-Liver X receptor expression was suppressed in all tissues except visceral adipose tissue, whereas PPARγ was lower in abdominal subcutaneous and visceral adipose tissue and PPARα only in abdominal subcutaneous. Testosterone treatment improved the expression (androgen receptor independent) of some targets but not all. These exploratory data suggest that androgen deficiency may reduce the buffering capability for glucose uptake and utilisation in abdominal subcutaneous and muscle and fatty acids in abdominal subcutaneous. This would lead to an overspill and uptake of excess glucose and triglycerides into visceral adipose tissue, liver and arterial walls.

  12. Impact of muscle wasting on survival in patients with liver cirrhosis.

    PubMed

    Kalafateli, Maria; Konstantakis, Christos; Thomopoulos, Konstantinos; Triantos, Christos

    2015-06-28

    Muscle wasting is defined as the progressive and generalized loss of muscle mass. Muscle depletion is a common feature of chronic liver disease found in approximately 40% of patients with cirrhosis. Its etiology is multifactorial subsequent to liver failure and its prevalence increases along with disease severity. Cross-sectional analytic morphometry using computed tomography (CT) scan or magnetic resonance imaging are considered by consensus the gold standards to assess muscle size in cirrhosis for research purposes because they are not biased by fluid accumulation. Several studies have assessed the impact of muscle wasting on overall survival of patients in the waiting list for liver transplantation and there is a general agreement that decreased muscle size assessed by CT scan is an independent predictor for mortality in cirrhosis. It has been proposed that the addition of cross-sectional muscle area into the Model for End-stage Liver Disease can increase its prognostic performance. Nevertheless, the use of CT scan in assessing muscle size is inappropriate for routine clinical practice and an alternative cost-effective, easy to use and accurate tool should be developed. In conclusion, muscle wasting has a detrimental impact on survival of patients with cirrhosis and, thus, it remains to be elucidated if nutritional interventions and exercise could improve muscle wasting and, subsequently, survival in this setting.

  13. Glucose and Fructose Have Sugar-Specific Effects in Both Liver and Skeletal Muscle In Vivo: A Role for Liver Fructokinase

    PubMed Central

    Fernández-Novell, Josep M.; Ramió-Lluch, Laura; Orozco, Anna; Gómez-Foix, Anna M.; Guinovart, Joan J.; Rodríguez-Gil, Joan E.

    2014-01-01

    We examined glucose and fructose effects on serine phosphorylation levels of a range of proteins in rat liver and muscle cells. For this, healthy adult rats were subjected to either oral glucose or fructose loads. A mini-array system was utilized to determine serine phosphorylation levels of liver and skeletal muscle proteins. A glucose oral load of 125 mg/100 g body weight (G 1/2) did not induce changes in phosphorylated serines of the proteins studied. Loading with 250 mg/100 g body weight of fructose (Fr), which induced similar glycemia levels as G 1/2, significantly increased serine phosphorylation of liver cyclin D3, PI3 kinase/p85, ERK-2, PTP2 and clusterin. The G 1/2 increased serine levels of the skeletal muscle proteins cyclin H, Cdk2, IRAK, total PKC, PTP1B, c-Raf 1, Ras and the β-subunit of the insulin receptor. The Fr induced a significant increase only in muscle serine phosphorylation of PI3 kinase/p85. The incubation of isolated rat hepatocytes with 10 mM glucose for 5 min significantly increased serine phosphorylation of 31 proteins. In contrast, incubation with 10 mM fructose produced less intense effects. Incubation with 10 mM glucose plus 75 µM fructose counteracted the effects of the incubation with glucose alone, except those on Raf-1 and Ras. Less marked effects were detected in cultured muscle cells incubated with 10 mM glucose or 10 mM glucose plus 75 µM fructose. Our results suggest that glucose and fructose act as specific functional modulators through a general mechanism that involves liver-generated signals, like micromolar fructosemia, which would inform peripheral tissues of the presence of either glucose- or fructose-derived metabolites. PMID:25330076

  14. Glucose and fructose have sugar-specific effects in both liver and skeletal muscle in vivo: a role for liver fructokinase.

    PubMed

    Fernández-Novell, Josep M; Ramió-Lluch, Laura; Orozco, Anna; Gómez-Foix, Anna M; Guinovart, Joan J; Rodríguez-Gil, Joan E

    2014-01-01

    We examined glucose and fructose effects on serine phosphorylation levels of a range of proteins in rat liver and muscle cells. For this, healthy adult rats were subjected to either oral glucose or fructose loads. A mini-array system was utilized to determine serine phosphorylation levels of liver and skeletal muscle proteins. A glucose oral load of 125 mg/100 g body weight (G 1/2) did not induce changes in phosphorylated serines of the proteins studied. Loading with 250 mg/100 g body weight of fructose (Fr), which induced similar glycemia levels as G 1/2, significantly increased serine phosphorylation of liver cyclin D3, PI3 kinase/p85, ERK-2, PTP2 and clusterin. The G 1/2 increased serine levels of the skeletal muscle proteins cyclin H, Cdk2, IRAK, total PKC, PTP1B, c-Raf 1, Ras and the β-subunit of the insulin receptor. The Fr induced a significant increase only in muscle serine phosphorylation of PI3 kinase/p85. The incubation of isolated rat hepatocytes with 10 mM glucose for 5 min significantly increased serine phosphorylation of 31 proteins. In contrast, incubation with 10 mM fructose produced less intense effects. Incubation with 10 mM glucose plus 75 µM fructose counteracted the effects of the incubation with glucose alone, except those on Raf-1 and Ras. Less marked effects were detected in cultured muscle cells incubated with 10 mM glucose or 10 mM glucose plus 75 µM fructose. Our results suggest that glucose and fructose act as specific functional modulators through a general mechanism that involves liver-generated signals, like micromolar fructosemia, which would inform peripheral tissues of the presence of either glucose- or fructose-derived metabolites.

  15. Sarcopenia and liver transplant: The relevance of too little muscle mass.

    PubMed

    Kallwitz, Eric R

    2015-10-21

    Loss of muscle mass and function is a common occurrence in both patients with decompensated cirrhosis and those undergoing liver transplantation. Sarcopenia is associated with morbidity and mortality before and after liver transplantation. The ability of skeletal muscle mass to recover after transplant is questionable, and long term adverse events associated with persistent sarcopenia have not been well studied. Limited data is available examining mechanisms by which decreased muscle mass might develop. It is not clear which interventions might reduce the prevalence of sarcopenia and associated health burdens. However, measures to either decrease portal hypertension or improve nutrition appear to have benefit. Research on sarcopenia in the liver transplant setting is hampered by differing methodology to quantify muscle mass and varied thresholds determining the presence of sarcopenia. One area highlighted in this review is the heterogeneity used when defining sarcopenia. The health consequences, clinical course and potential pathophysiologic mechanisms of sarcopenia in the setting of cirrhosis and liver transplantation are further discussed.

  16. Enzyme activities in plasma, kidney, liver, and muscle of five avian species

    USGS Publications Warehouse

    Franson, J.C.; Murray, H.C.; Bunck, C.

    1985-01-01

    Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) were determined in plasma, kidney, liver, and muscle from five species of captive birds. Few differences occurred in plasma activities between sexes but considerable differences occurred between species. All five enzymes were detected in each of the tissues sampled. Relative enzyme activities in liver, kidney, and muscle were similar for each species. CPK activity was much higher in muscle than in liver or kidney and, of the five enzymes studied, may be the best indicator of muscle damage. Most of the other enzymes were more evenly distributed among the three tissues, and no organ-specific enzyme could be identified for liver or kidney. Because of interspecific variations in plasma enzyme activities, it is important to establish baseline values for each species to ensure accurate interpretation of results.

  17. Opposite effects of β2-adrenoceptor gene deletion on insulin signaling in liver and skeletal muscle.

    PubMed

    Cipolletta, E; Del Giudice, C; Santulli, G; Trimarco, B; Iaccarino, G

    2017-07-01

    β2-Adrenoceptors (β2-ARs) are G protein-coupled receptors (GPCRs) expressed in the major insulin target tissues. The interplay between β2-AR and insulin pathways is involved in the maintenance of glucose homeostasis. The aim of this study was to explore the consequences of β2-ARs deletion on insulin sensitivity and insulin signaling cascade in metabolically active tissues. We evaluated glucose homeostasis in skeletal muscle and liver of β2-AR-null mice (β2-AR(-/-)) by performing in vivo (glucose tolerance test and insulin tolerance test) and ex vivo (glucose uptake and glycogen determination) experiments. β2-AR gene deletion is associated with hepatic insulin resistance and preserved skeletal muscle insulin sensitivity. Importantly, we demonstrate that hepatic β2-AR regulates insulin-induced AKT activation via Grb2-mediated SRC recruitment through a Gi-independent mechanism. β-AR stimulation contributes to the development of early stages of insulin resistance progression in the liver. Our findings indicate that the cross-talk between β2-AR and insulin signaling represents a fundamental target towards the development of novel therapeutic approaches to treat type 2 diabetes and metabolic syndrome. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  18. Metabolic effects of the iodothyronine functional analogue TRC150094 on the liver and skeletal muscle of high-fat diet fed overweight rats: an integrated proteomic study.

    PubMed

    Silvestri, Elena; Glinni, Daniela; Cioffi, Federica; Moreno, Maria; Lombardi, Assunta; de Lange, Pieter; Senese, Rosalba; Ceccarelli, Michele; Salzano, Anna Maria; Scaloni, Andrea; Lanni, Antonia; Goglia, Fernando

    2012-07-06

    A novel functional iodothyronine analogue, TRC150094, which has a much lower potency toward thyroid hormone receptor (α1/β1) activation than triiodothyronine, has been shown to be effective at reducing adiposity in rats simultaneously receiving a high-fat diet (HFD). Here, by combining metabolic, functional and proteomic analysis, we studied how the hepatic and skeletal muscle phenotypes might respond to TRC150094 treatment in HFD-fed overweight rats. Drug treatment increased both the liver and skeletal muscle mitochondrial oxidative capacities without altering mitochondrial efficiency. Coherently, in terms of individual respiratory in-gel activity, blue-native analysis revealed an increased activity of complex V in the liver and of complexes II and V in tibialis muscle in TCR150094-treated animals. Subsequently, the identification of differentially expressed proteins and the analysis of their interrelations gave an integrated view of the phenotypic/metabolic adaptations occurring in the liver and muscle proteomes during drug treatment. TRC150094 significantly altered the expression of several proteins involved in key liver metabolic pathways, including amino acid and nitrogen metabolism, and fructose and mannose metabolism. The canonical pathways most strongly influenced by TRC150094 in tibialis muscle included glycolysis and gluconeogenesis, amino acid, fructose and mannose metabolism, and cell signaling. The phenotypic/metabolic influence of TRC150094 on the liver and skeletal muscle of HFD-fed overweight rats suggests the potential clinical application of this iodothyronine analogue in ameliorating metabolic risk parameters altered by diet regimens.

  19. Total mercury in liver and muscle tissue of two coastal sharks from the northwest of Mexico.

    PubMed

    Hurtado-Banda, Rocío; Gomez-Alvarez, Agustín; Márquez-Farías, J Fernando; Cordoba-Figueroa, Marcial; Navarro-García, Gerardo; Medina-Juárez, Luis Angel

    2012-06-01

    Total mercury (THg) in liver and muscle of three costal sharks from Mexico were evaluated. The highest concentrations of THg in muscle tissue of juveniles were found in Sphyrna lewini (0.82 ± 0.33 mg kg(-1) wet basis). Rhizoprionodon longurio adults had the highest concentrations (0.92 ± 1.03 mg kg(-1)). THg concentrations in liver were low compared to those found in muscle tissue; higher levels were found in liver of juvenile S. lewini (0.250 ± 0.07 mg kg(-1)). Results showed that 35 % of muscle tissue samples are above the precautionary limit (0.50 mg kg(-1) of THg) and a 7 % exceeded the maximum limit for human consumption (1 mg kg(-1)).

  20. Peripheral effects of the endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle.

    PubMed

    Silvestri, Cristoforo; Ligresti, Alessia; Di Marzo, Vincenzo

    2011-09-01

    The endocannabinoid system (ECS) is composed of lipid signalling ligands, their G-protein coupled receptors and the enzymes involved in ligand generation and metabolism. Increasingly, the ECS is emerging as a critical agent of energy metabolism regulation through its ability to modulate caloric intake centrally as well as nutrient transport, cellular metabolism and energy storage peripherally. Visceral obesity has been associated with an upregulation of ECS activity in several systems and inhibition of the ECS, either pharmacologically or genetically, results in decreased energy intake and increased metabolic output. This review aims to summarize the recent advances that have been made regarding our understanding of the role the ECS plays in crucial peripheral systems pertaining to energy homeostasis: adipose tissues, the liver and skeletal muscle.

  1. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman W.

    1987-01-01

    New muscle tissue culture techniques were developed to grow embryonic skeletal myofibers which are able to differentiate into more adultlike myofibers. Studies on mechanical simulation of cultured muscle cell growth will now be more directly applicable to mechanically-induced growth in adult muscle, and lead to better models for understanding muscle tissue atrophy caused by disuse in the microgravity of space.

  2. Mitochondrial respiration in muscle and liver from cold-acclimated hypothyroid rats.

    PubMed

    Zaninovich, Angel A; Rebagliati, Ines; Raices, Marcela; Ricci, Conrado; Hagmuller, Karl

    2003-10-01

    The effects of long-term cold exposure on muscle and liver mitochondrial oxygen consumption in hypothyroid and normal rats were examined. Thyroid ablation was performed after 8-wk acclimation to 4 degrees C. Hypothyroid and normal controls remained in the cold for an additional 8 wk. At the end of 16-wk cold exposure, all hypothyroid rats were alive and normothermic and had normal body weight. At ambient temperature (24 degrees C), thyroid ablation induced a 65% fall in muscle mitochondrial oxygen consumption, which was reversed by thyroxine but not by norepinephrine administration. After cold acclimation was reached, suppression of thyroid function reduced muscle mitochondrial respiration by 30%, but the hypothyroid values remained about threefold higher than those in hypothyroid muscle in the warm. Blockade of beta- and alpha1-adrenergic receptors in both hypothyroid and normal rats produced hypothermia in vivo and a fall in muscle, liver, and brown adipose tissue mitochondria respiration in vitro. In normal rats, cold acclimation enhanced muscle respiration by 35%, in liver 18%, and in brown adipose tissue 450% over values in the warm. The results demonstrate that thyroid hormones, in the presence of norepinephrine, are major determinants of thermogenic activity in muscle and liver of cold-acclimated rats. After thyroid ablation, cold-induced nonshivering thermogenesis replaced 3,5,3'-triiodothyronine-induced thermogenesis, and normal body temperature was maintained.

  3. Liver kinase B1 inhibits the expression of inflammation-related genes postcontraction in skeletal muscle

    PubMed Central

    Chen, Ting; Moore, Timothy M.; Ebbert, Mark T. W.; McVey, Natalie L.; Madsen, Steven R.; Hallowell, David M.; Harris, Alexander M.; Char, Robin E.; Mackay, Ryan P.; Hancock, Chad R.; Hansen, Jason M.; Kauwe, John S.

    2016-01-01

    Skeletal muscle-specific liver kinase B1 (LKB1) knockout mice (skmLKB1-KO) exhibit elevated mitogen-activated protein kinase (MAPK) signaling after treadmill running. MAPK activation is also associated with inflammation-related signaling in skeletal muscle. Since exercise can induce muscle damage, and inflammation is a response triggered by damaged tissue, we therefore hypothesized that LKB1 plays an important role in dampening the inflammatory response to muscle contraction, and that this may be due in part to increased susceptibility to muscle damage with contractions in LKB1-deficient muscle. Here we studied the inflammatory response and muscle damage with in situ muscle contraction or downhill running. After in situ muscle contractions, the phosphorylation of both NF-κB and STAT3 was increased more in skmLKB1-KO vs. wild-type (WT) muscles. Analysis of gene expression via microarray and RT-PCR shows that expression of many inflammation-related genes increased after contraction only in skmLKB1-KO muscles. This was associated with mild skeletal muscle fiber membrane damage in skmLKB1-KO muscles. Gene markers of oxidative stress were also elevated in skmLKB1-KO muscles after contraction. Using the downhill running model, we observed significantly more muscle damage after running in skmLKB1-KO mice, and this was associated with greater phosphorylation of both Jnk and STAT3 and increased expression of SOCS3 and Fos. In conclusion, we have shown that the lack of LKB1 in skeletal muscle leads to an increased inflammatory state in skeletal muscle that is exacerbated by muscle contraction. Increased susceptibility of the muscle to damage may underlie part of this response. PMID:26796753

  4. Liver kinase B1 inhibits the expression of inflammation-related genes postcontraction in skeletal muscle.

    PubMed

    Chen, Ting; Moore, Timothy M; Ebbert, Mark T W; McVey, Natalie L; Madsen, Steven R; Hallowell, David M; Harris, Alexander M; Char, Robin E; Mackay, Ryan P; Hancock, Chad R; Hansen, Jason M; Kauwe, John S; Thomson, David M

    2016-04-15

    Skeletal muscle-specific liver kinase B1 (LKB1) knockout mice (skmLKB1-KO) exhibit elevated mitogen-activated protein kinase (MAPK) signaling after treadmill running. MAPK activation is also associated with inflammation-related signaling in skeletal muscle. Since exercise can induce muscle damage, and inflammation is a response triggered by damaged tissue, we therefore hypothesized that LKB1 plays an important role in dampening the inflammatory response to muscle contraction, and that this may be due in part to increased susceptibility to muscle damage with contractions in LKB1-deficient muscle. Here we studied the inflammatory response and muscle damage with in situ muscle contraction or downhill running. After in situ muscle contractions, the phosphorylation of both NF-κB and STAT3 was increased more in skmLKB1-KO vs. wild-type (WT) muscles. Analysis of gene expression via microarray and RT-PCR shows that expression of many inflammation-related genes increased after contraction only in skmLKB1-KO muscles. This was associated with mild skeletal muscle fiber membrane damage in skmLKB1-KO muscles. Gene markers of oxidative stress were also elevated in skmLKB1-KO muscles after contraction. Using the downhill running model, we observed significantly more muscle damage after running in skmLKB1-KO mice, and this was associated with greater phosphorylation of both Jnk and STAT3 and increased expression of SOCS3 and Fos. In conclusion, we have shown that the lack of LKB1 in skeletal muscle leads to an increased inflammatory state in skeletal muscle that is exacerbated by muscle contraction. Increased susceptibility of the muscle to damage may underlie part of this response.

  5. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.

    1987-01-01

    Muscle tissue culture techniques were developed to grow skeletal myofibers which differentiate into more adult-like myofibers. Mechanical simulation studies of these muscle cells in a newly developed mechanical cell simulator can now be performed to study growth processes in skeletal muscle. Conditions in the mechanical cell simulator were defined where mechanical activity can either prevent muscle wasting or stimulate muscle growth. The role of endogenous and exogenous growth factors in tension-induced muscle growth is being investigated under the defined conditions of tissue culture.

  6. Distribution of cadmium in leg muscle and liver of game birds from Serbia

    NASA Astrophysics Data System (ADS)

    Nikolić, D.; Đinović-Stojanović, J.; Stefanović, S.; Radičević, T.; Trbović, D.; Spirić, D.; Janković, S.

    2017-09-01

    The aim of this study was to present the distribution of cadmium (Cd) levels in leg muscle and liver of game birds. Samples (n=464) of: pheasants (n=182), mallards (n=25), Eurasian jay (n=7), partridges (n=5), woodcocks (n=8) and common quail (n=5) were collected during regular hunting seasons within the Serbian National Residue Monitoring Program from 2013 to 2016. Analysis of Cd was performed by ICP-MS. In all liver samples, Cd levels were above the limit of detection (LOD=0.001 mg/kg) while in 66.4% of muscle samples, Cd was detected. Statistical analysis showed significant differences between Cd levels in leg muscle and liver of woodcocks and others game birds. The highest mean Cd level was observed in muscle samples of woodcocks (0.042 mg/kg). The lowest mean Cd levels in liver were observed in common quails (0.130 mg/kg) and mallards (0.160 mg/kg) while the highest levels were measured in woodcocks (1.247 mg/kg) and pheasants (0.262 mg/kg). During four years of the Serbian National Residue Monitoring Program, leg muscle samples of woodcocks (n=3), liver samples of pheasants (n=23), woodcocks (n=6) and mallards (n=3) exceeded the maximum residue limit (MRL).

  7. Distribution of mercury in leg muscle and liver of game birds from Serbia

    NASA Astrophysics Data System (ADS)

    Janković, S.; Nikolić, D.; Stefanović, S.; Radičević, T.; Đinović-Stojanović, J.; Spirić, D.; Tanković, S.

    2017-09-01

    The purpose of this study was to determine the distribution of Hg levels in leg muscle and liver of game birds collected within the Serbian National residue monitoring program from 2013 to 2016. Hg levels in samples (n=464) of: pheasants (n=182), mallard (n=25), Eurasian jay (n=7), partridges (n=5) and woodcocks (n=8) were determined by ICPMS. The highest mean Hg levels were observed in leg muscle samples of woodcocks (0.071 mg/kg) and mallard (0.059 mg/kg). The lowest mean Hg level in liver was determined in partridges (0.008 mg/kg) while the highest was in pheasants (0.262 mg/kg) and mallard (0.161 mg/kg). Statistical analysis showed significantly differences between Hg levels in liver of woodcocks and mallard, as well as between them and livers of other analysed game birds. During the four years (2013-2016), 87.5% of leg muscle and 50% of woodcock livers had Hg levels that exceeded the MRL, while in mallard muscle and liver those percentages were 36% and 40%, respectively.

  8. Muscles involved in naris dilation and nose motion in rat

    PubMed Central

    Deschênes, Martin; Haidarliu, Sebastian; Demers, Maxime; Moore, Jeffrey; Kleinfeld, David; Ahissar, Ehud

    2016-01-01

    In a number of mammals muscle dilator nasi (naris) is known as a muscle that reduces nasal airflow resistance by dilating the nostrils. Here we show that in rats the tendon of this muscle inserts into the aponeurosis above the nasal cartilage. Electrical stimulation of this muscle lifts the nose and deflects it sideway towards the side of stimulation, but does not change the size of the nares. In the head-fixed alert rat, electromyographic activity of muscle dilator nasi is tightly coupled to nose motion, not to opening of the nares. Yet, contraction of muscle dilator nasi occurs during the pre-inspiratory phase of the respiratory cycle, suggesting a role in sniffing and sampling odorants. We also show that opening of the nares results from contraction of pars maxillaris profunda of the muscle nasolabialis profundus. This muscle attaches to the outer wall of the nasal cartilage and to the plate of the mystacial pad. Contraction of this muscle exerts a dual action: it pulls the lateral nasal cartilage outwardly, thus dilating the naris, and it drags the plate of the mystacial pad rostralward, provoking a slight retraction of the whiskers. On the basis of these results, we propose that muscle dilator nasi of the rat be renamed muscle deflector nasi, and that pars maxillaris profunda of the muscle nasolabialis profundus be named muscle dilator nasi. PMID:25257748

  9. Diagnosis of Liver Involvement in Primary Sjögren Syndrome

    PubMed Central

    Zeron, Pilar Brito; Retamozo, Soledad; Bové, Albert; Kostov, Belchin Adriyanov; Sisó, Antoni

    2013-01-01

    Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sjögren syndrome (SS). In the 1990s, a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease, liver function and a complete panel of autoantibodies. Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS. The most recent studies have shown that, after eliminating hepatotoxic drugs and fatty liver disease, the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases. The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important, since the two processes require different therapeutic approaches and have different prognoses. With respect to viral infections, chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area, while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries. After eliminating viral hepatitis, primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS. PBC-related SS patients may have a broad spectrum of abnormalities of the liver, including having no clinical or analytical data suggestive of liver disease. Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I), and nearly 10% of these patients have an AIH-PBC overlap. Finally, IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis, especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present. PMID:26355632

  10. Molecular mechanisms of lipid-induced insulin resistance in muscle, liver and vasculature.

    PubMed

    Krebs, M; Roden, M

    2005-11-01

    Increased body fat content correlates with insulin resistance and is a key feature of type 2 diabetes. Excessive intake of fat results in deposition of lipids not only in fat tissue but also in skeletal muscle and liver. Subsequently, both plasma and intracellular concentrations of free fatty acids and their metabolites rise and activate signal transduction pathways, which will induce inflammation and impair insulin signalling. Furthermore, elevated circulating lipids impair endothelial function and fibrinolysis, which contributes to the development of vascular disease. Thus, therapeutic strategies aiming at reduction of (intracellular) lipid availability in skeletal muscle and liver and pharmacological modulation of the signalling pathways activated by increased lipid stores represent promising targets for future treatment of insulin resistance and prevention of its complications. This review focuses on the effects of increased lipid availability on the regulation of glucose metabolism in skeletal muscle and liver as well as on vascular function.

  11. Developmental changes of Insulin-like growth factors in the liver and muscle of chick embryos.

    PubMed

    Liu, Yanli; Guo, Wei; Pu, Zhenyu; Li, Xueyuan; Lei, Xinyu; Yao, Junhu; Yang, Xiaojun

    2016-06-01

    The insulin-like growth factors ( IGFS: ) are synthesized in tissues and play an important role in embryonic development of avian via autocrine/paracrine mechanisms. In the study, mRNA expression of IGFs were detected by real-time PCR in the muscle and liver from d 10 to 20 of chick embryo ( E10: to E20: ). Methylation of IGF1 promoter in the muscle was analyzed by bisulfite sequencing PCR as well as IGF2 promoter in the liver. These results showed that there was obviously IGF1 expression in liver at E19 and E20. The higher IGF1 expression in muscle was found during E15 to E18 with the peak on E17, and then declined. Correspondingly, the lowest methylation level of IGF1 promoter was detectable on the same embryonic d 17. Expression of IGF2 in muscle increased gradually during embryonic growth and showed higher level in the later stages (E17 to E20) when IGF1 expression began to decrease. IGF2 expression in liver reached the first peak on E14, then declined but gradually elevated from E17. IGF2 promoter methylation in liver showed gradual decline on d 12, 15, 17 and 19 of incubation, meanwhile IGF2 expression of liver increased gradually. These results suggested that IGF1 and IGF2 might separately be more important for muscle and liver growth in chick embryonic development. Variation of IGFs expression during the incubation might be concerned with the methylation of gene promoter. The profile of IGFs expression in chick embryonic tissues may be meaningful for understanding organ growth and embryonic development in chick. © 2016 Poultry Science Association Inc.

  12. Acute Onset Significant Muscle Weakness in a Patient Awaiting Liver Transplantation: Look for Statins.

    PubMed

    Choudhary, Narendra S; Saigal, Sanjiv; Saraf, Neeraj; Soin, Arvinder S

    2017-03-01

    Statins are commonly used drugs in patients with liver and cardiac disease. Statin-induced severe myopathy is a very uncommon presentation and rhabdomyolysis may occur in extreme cases which leads to renal failure. Patients with comorbidities like diabetes, hypothyroidism, and liver disease have higher chances of development of statin-induced myopathy. We describe a case of Child's C cirrhosis wherein the patient had acute onset significant muscle weakness and improved on statin discontinuation.

  13. [Roentgenoradiological and ultrasonic diagnosis of liver and spleen involvement in patients with Hodgkin's disease].

    PubMed

    Balashov, A T; Mendeleev, I M

    1988-01-01

    A combined study including selective angiography of the liver and spleen, angioscintigraphy with 99mTc-TCK-5, polypositional scintigraphy with 99mTc-frosstimag-phytate, and ultrasonic scanning was conducted to detect specific liver and splenic involvement in 57 patients with Hodgkin's disease, CT was performed in 4 patients. A high diagnostic value of all methods was shown in macronodal liver involvement (node sizes over 3 cm); of ultrasonic scanning--in the detection of nodes in the liver (node sizes from 1 to 3 cm); of ultrasonic scanning, angiography and angioscintigraphy--in nodal splenic involvement. Signs of diffuse-infiltrative liver involvement detected in angiography and angioscintigraphy were described. The informative value of ultrasonic scanning and CT in this type of involvement was much lower.

  14. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    PubMed

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  15. Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis.

    PubMed

    López-Lirola, A; González-Reimers, E; Martín Olivera, R; Santolaria-Fernández, F; Galindo-Martín, L; Abreu-González, P; González-Hernández, T; Valladares-Parrilla, F

    2003-12-01

    Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.

  16. A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling

    PubMed Central

    Shimizu, Noriaki; Maruyama, Takako; Yoshikawa, Noritada; Matsumiya, Ryo; Ma, Yanxia; Ito, Naoki; Tasaka, Yuki; Kuribara-Souta, Akiko; Miyata, Keishi; Oike, Yuichi; Berger, Stefan; Schütz, Günther; Takeda, Shin’ichi; Tanaka, Hirotoshi

    2015-01-01

    Skeletal muscle has a pleiotropic role in organismal energy metabolism, for example, by storing protein as an energy source, or by excreting endocrine hormones. Muscle proteolysis is tightly controlled by the hypothalamus-pituitary-adrenal signalling axis via a glucocorticoid-driven transcriptional programme. Here we unravel the physiological significance of this catabolic process using skeletal muscle-specific glucocorticoid receptor (GR) knockout (GRmKO) mice. These mice have increased muscle mass but smaller adipose tissues. Metabolically, GRmKO mice show a drastic shift of energy utilization and storage in muscle, liver and adipose tissues. We demonstrate that the resulting depletion of plasma alanine serves as a cue to increase plasma levels of fibroblast growth factor 21 (FGF21) and activates liver-fat communication, leading to the activation of lipolytic genes in adipose tissues. We propose that this skeletal muscle-liver-fat signalling axis may serve as a target for the development of therapies against various metabolic diseases, including obesity. PMID:25827749

  17. Histochemical localization of rhodanese activity in rat liver and skeletal muscle.

    PubMed

    Devlin, D J; Mills, J W; Smith, R P

    1989-02-01

    A previously described histochemical technique was applied to the localization of rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) activity in rat skeletal muscle and liver. The physiological function of rhodanese is controversial, but it and other sulfurtransferases can catalyze the conversion of cyanide to the much less toxic thiocyanate. The volume of distribution of cyanide in human and dog is said to correspond roughly to the blood volume. Because of this and other observations, it was hypothesized that sulfurtransferase activity associated with the vascular endothelium on smooth muscle layers of blood vessels might play a role in cyanide detoxification. However, little enzyme activity as identified histochemically was associated with those sites in comparison with others examined. As expected, high activity was found in the liver and moderately high levels were present in skeletal muscle. In muscles sectioned longitudinally, points of rhodanese staining occurred in linear arrays along the lengths of the muscle fiber corresponding to the location of mitochondria within the fiber. The original technique called for incubation of tissue sections with both thiosulfate and cyanide. When thiosulfate was omitted, staining for rhodanese activity was still clearly identifiable in both liver and muscle sections with cyanide alone. In muscle sections the inclusion of both thiosulfate and cyanide resulted in a preferential staining of type I fibers presumably because of their higher content of mitochondria. Thus, this technique is a potential alternative to the NADH dehydrogenase stain for distinguishing between type I and type II muscle fibers. Incubation of tissue sections with only thiosulfate produced results that did not appear to differ from those obtained when both substrates were omitted. From these observations it may be inferred that the endogenous pool of sulfane-sulfur available to sulfurtransferases is larger than any alleged endogenous pool of cyanide

  18. The activation of protein degradation in muscle by Ca2+ or muscle injury does not involve a lysosomal mechanism.

    PubMed Central

    Furuno, K; Goldberg, A L

    1986-01-01

    By use of different inhibitors, we distinguished three proteolytic processes in rat skeletal muscle. When soleus muscles maintained under tension were exposed to the calcium ionophore A23187 or were incubated under no tension in the presence of Ca2+, net protein breakdown increased by 50-80%. Although leupeptin and E-64 inhibit this acceleration of protein breakdown almost completely, other agents that prevent lysosomal function, such as methylamine or leucine methyl ester, did not inhibit this effect. A similar increase in net proteolysis occurred in muscle fibres injured by cutting, and this response was also inhibited by leupeptin, but not by methylamine. In contrast, all these inhibitors markedly decreased the 2-fold increase in protein breakdown induced by incubating muscles without insulin and leucine, isoleucine and valine. In addition, the low rate of proteolysis seen in muscles under passive tension in complete medium was not affected by any of these inhibitors. Thus the basal degradative process in muscle does not involve lysosomes or thiol proteinases, and muscle can enhance protein breakdown by two mechanisms: lack of insulin and nutrients enhances a lysosomal process in muscle, as in other cells, whereas Ca2+ and muscle injury activate a distinct pathway involving cytosolic thiol proteinase(s). PMID:3099758

  19. Sarcopenia and liver transplant: The relevance of too little muscle mass

    PubMed Central

    Kallwitz, Eric R

    2015-01-01

    Loss of muscle mass and function is a common occurrence in both patients with decompensated cirrhosis and those undergoing liver transplantation. Sarcopenia is associated with morbidity and mortality before and after liver transplantation. The ability of skeletal muscle mass to recover after transplant is questionable, and long term adverse events associated with persistent sarcopenia have not been well studied. Limited data is available examining mechanisms by which decreased muscle mass might develop. It is not clear which interventions might reduce the prevalence of sarcopenia and associated health burdens. However, measures to either decrease portal hypertension or improve nutrition appear to have benefit. Research on sarcopenia in the liver transplant setting is hampered by differing methodology to quantify muscle mass and varied thresholds determining the presence of sarcopenia. One area highlighted in this review is the heterogeneity used when defining sarcopenia. The health consequences, clinical course and potential pathophysiologic mechanisms of sarcopenia in the setting of cirrhosis and liver transplantation are further discussed. PMID:26494955

  20. Supplementation with l-carnitine downregulates genes of the ubiquitin proteasome system in the skeletal muscle and liver of piglets.

    PubMed

    Keller, J; Ringseis, R; Koc, A; Lukas, I; Kluge, H; Eder, K

    2012-01-01

    Supplementation of carnitine has been shown to improve performance characteristics such as protein accretion in growing pigs. The molecular mechanisms underlying this phenomenon are largely unknown. Based on recent results from DNA microchip analysis, we hypothesized that carnitine supplementation leads to a downregulation of genes of the ubiquitin proteasome system (UPS). The UPS is the most important system for protein breakdown in tissues, which in turn could be an explanation for increased protein accretion. To test this hypothesis, we fed sixteen male, four-week-old piglets either a control diet or the same diet supplemented with carnitine and determined the expression of several genes involved in the UPS in the liver and skeletal muscle. To further determine whether the effects of carnitine on the expression of genes of the UPS are mediated directly or indirectly, we also investigated the effect of carnitine on the expression of genes of the UPS in cultured C2C12 myotubes and HepG2 liver cells. In the liver of piglets fed the carnitine-supplemented diet, the relative mRNA levels of atrogin-1, E214k and Psma1 were lower than in those of the control piglets (P < 0.05). In skeletal muscle, the relative mRNA levels of atrogin-1, MuRF1, E214k, Psma1 and ubiquitin were lower in piglets fed the carnitine-supplemented diet than that in control piglets (P < 0.05). Incubating C2C12 myotubes and HepG2 liver cells with increasing concentrations of carnitine had no effect on basal and/or hydrocortisone-stimulated mRNA levels of genes of the UPS. In conclusion, this study shows that dietary carnitine decreases the transcript levels of several genes involved in the UPS in skeletal muscle and liver of piglets, whereas carnitine has no effect on the transcript levels of these genes in cultivated HepG2 liver cells and C2C12 myotubes. These data suggest that the inhibitory effect of carnitine on the expression of genes of the UPS is mediated indirectly, probably via modulating

  1. Mitochondrial Involvement and Impact in Aging Skeletal Muscle

    PubMed Central

    Hepple, Russell T.

    2014-01-01

    Atrophy is a defining feature of aging skeletal muscle that contributes to progressive weakness and an increased risk of mobility impairment, falls, and physical frailty in very advanced age. Amongst the most frequently implicated mechanisms of aging muscle atrophy is mitochondrial dysfunction. Recent studies employing methods that are well-suited to interrogating intrinsic mitochondrial function find that mitochondrial respiration and reactive oxygen species emission changes are inconsistent between aging rat muscles undergoing atrophy and appear normal in human skeletal muscle from septuagenarian physically active subjects. On the other hand, a sensitization to permeability transition seems to be a general property of atrophying muscle with aging and this effect is even seen in atrophying muscle from physically active septuagenarian subjects. In addition to this intrinsic alteration in mitochondrial function, factors extrinsic to the mitochondria may also modulate mitochondrial function in aging muscle. In particular, recent evidence implicates oxidative stress in the aging milieu as a factor that depresses respiratory function in vivo (an effect that is not present ex vivo). Furthermore, in very advanced age, not only does muscle atrophy become more severe and clinically relevant in terms of its impact, but also there is evidence that this is driven by an accumulation of severely atrophied denervated myofibers. As denervation can itself modulate mitochondrial function and recruit mitochondrial-mediated atrophy pathways, future investigations need to address the degree to which skeletal muscle mitochondrial alterations in very advanced age are a consequence of denervation, rather than a primary organelle defect, to refine our understanding of the relevance of mitochondria as a therapeutic target at this more advanced age. PMID:25309422

  2. [Muscle weakness and early stages of liver failure in a 22-year-old man].

    PubMed

    Scheicht, D; Werthmann, M L; Zeglam, S; Holtmeier, J; Holtmeier, W; Strunk, J

    2013-08-01

    A 22-year-old man without pre-existing medical conditions presented to our hospital with a progressive reduction of his physical overall performance, muscle weakness of the extremities, and diarrhea for the last 2 months concomitant with elevated liver enzymes and creatine kinase activity. After ruling out infectious diseases, neoplasia, and autoimmune disorders as a cause of these symptoms, the histology of liver and muscle samples led us to suspect a diagnosis of a rare lipid metabolism disorder. Molecular biologic testing provided the diagnosis of multiple acyl-coA dehydrogenase deficiency with ubiquinone deficiency and late onset. The course of disease was complicated by liver failure and severe pneumonia requiring ventilatory assistance. With the substitution of riboflavin and ubiquinone, the patient showed a gradual recovery of his clinical presentation and an improvement of his laboratory tests. A congenital lipid metabolic disorder might be a rare cause of severe myopathy and hepatopathy in a young adult.

  3. Thermal manipulation during embryogenesis has long-term effects on muscle and liver metabolism in fast-growing chickens.

    PubMed

    Loyau, Thomas; Métayer-Coustard, Sonia; Berri, Cécile; Crochet, Sabine; Cailleau-Audouin, Estelle; Sannier, Mélanie; Chartrin, Pascal; Praud, Christophe; Hennequet-Antier, Christelle; Rideau, Nicole; Couroussé, Nathalie; Mignon-Grasteau, Sandrine; Everaert, Nadia; Duclos, Michel Jacques; Yahav, Shlomo; Tesseraud, Sophie; Collin, Anne

    2014-01-01

    Fast-growing chickens have a limited ability to tolerate high temperatures. Thermal manipulation during embryogenesis (TM) has previously been shown to lower chicken body temperature (Tb) at hatching and to improve thermotolerance until market age, possibly resulting from changes in metabolic regulation. The aim of this study was to evaluate the long-term effects of TM (12 h/d, 39.5°C, 65% RH from d 7 to 16 of embryogenesis vs. 37.8°C, 56% RH continuously) and of a subsequent heat challenge (32°C for 5 h at 34 d) on the mRNA expression of metabolic genes and cell signaling in the Pectoralis major muscle and the liver. Gene expression was analyzed by RT-qPCR in 8 chickens per treatment, characterized by low Tb in the TM groups and high Tb in the control groups. Data were analyzed using the general linear model of SAS considering TM and heat challenge within TM as main effects. TM had significant long-term effects on thyroid hormone metabolism by decreasing the muscle mRNA expression of deiodinase DIO3. Under standard rearing conditions, the expression of several genes involved in the regulation of energy metabolism, such as transcription factor PGC-1α, was affected by TM in the muscle, whereas for other genes regulating mitochondrial function and muscle growth, TM seemed to mitigate the decrease induced by the heat challenge. TM increased DIO2 mRNA expression in the liver (only at 21°C) and reduced the citrate synthase activity involved in the Krebs cycle. The phosphorylation level of p38 Mitogen-activated-protein kinase regulating the cell stress response was higher in the muscle of TM groups compared to controls. In conclusion, markers of energy utilization and growth were either changed by TM in the Pectoralis major muscle and the liver by thermal manipulation during incubation as a possible long-term adaptation limiting energy metabolism, or mitigated during heat challenge.

  4. Thermal Manipulation during Embryogenesis Has Long-Term Effects on Muscle and Liver Metabolism in Fast-Growing Chickens

    PubMed Central

    Loyau, Thomas; Métayer-Coustard, Sonia; Berri, Cécile; Crochet, Sabine; Cailleau-Audouin, Estelle; Sannier, Mélanie; Chartrin, Pascal; Praud, Christophe; Hennequet-Antier, Christelle; Rideau, Nicole; Couroussé, Nathalie; Mignon-Grasteau, Sandrine; Everaert, Nadia; Duclos, Michel Jacques; Yahav, Shlomo; Tesseraud, Sophie; Collin, Anne

    2014-01-01

    Fast-growing chickens have a limited ability to tolerate high temperatures. Thermal manipulation during embryogenesis (TM) has previously been shown to lower chicken body temperature (Tb) at hatching and to improve thermotolerance until market age, possibly resulting from changes in metabolic regulation. The aim of this study was to evaluate the long-term effects of TM (12 h/d, 39.5°C, 65% RH from d 7 to 16 of embryogenesis vs. 37.8°C, 56% RH continuously) and of a subsequent heat challenge (32°C for 5 h at 34 d) on the mRNA expression of metabolic genes and cell signaling in the Pectoralis major muscle and the liver. Gene expression was analyzed by RT-qPCR in 8 chickens per treatment, characterized by low Tb in the TM groups and high Tb in the control groups. Data were analyzed using the general linear model of SAS considering TM and heat challenge within TM as main effects. TM had significant long-term effects on thyroid hormone metabolism by decreasing the muscle mRNA expression of deiodinase DIO3. Under standard rearing conditions, the expression of several genes involved in the regulation of energy metabolism, such as transcription factor PGC-1α, was affected by TM in the muscle, whereas for other genes regulating mitochondrial function and muscle growth, TM seemed to mitigate the decrease induced by the heat challenge. TM increased DIO2 mRNA expression in the liver (only at 21°C) and reduced the citrate synthase activity involved in the Krebs cycle. The phosphorylation level of p38 Mitogen-activated-protein kinase regulating the cell stress response was higher in the muscle of TM groups compared to controls. In conclusion, markers of energy utilization and growth were either changed by TM in the Pectoralis major muscle and the liver by thermal manipulation during incubation as a possible long-term adaptation limiting energy metabolism, or mitigated during heat challenge. PMID:25180913

  5. Characteristic MRI Findings of upper Limb Muscle Involvement in Myotonic Dystrophy Type 1.

    PubMed

    Sugie, Kazuma; Sugie, Miho; Taoka, Toshio; Tonomura, Yasuyo; Kumazawa, Aya; Izumi, Tesseki; Kichikawa, Kimihiko; Ueno, Satoshi

    2015-01-01

    The objective of our study was to evaluate the relation between muscle MRI findings and upper limb weakness with grip myotonia in patients with myotonic dystrophy type 1 (DM1). Seventeen patients with DM1 were evaluated by manual muscle strength testing and muscle MRI of the upper limbs. Many DM1 patients presenting with decreased grasping power frequently showed high intensity signals in the flexor digitorum profundus (FDP) muscles on T1-weighted imaging. Patients presenting with upper limb weakness frequently also showed high intensity signals in the flexor pollicis longus, abductor pollicis longus, and extensor pollicis muscles. Disturbances of the distal muscles of the upper limbs were predominant in all DM1 patients. Some DM1 patients with a prolonged disease duration showed involvement of not only distal muscles but also proximal muscles in the upper limbs. Muscle involvement of the upper limbs on MRI strongly correlated positively with the disease duration or the numbers of CTG repeats. To our knowledge, this is the first study to provide a detailed description of the distribution and severity of affected muscles of the upper limbs on MRI in patients with DM1. We conclude that muscle MRI findings are very useful for identifying affected muscles and predicting the risk of muscle weakness in the upper limbs of DM1 patients.

  6. Lanreotide Reduces Liver Volume, But Might Not Improve Muscle Wasting or Weight Loss, in Patients With Symptomatic Polycystic Liver Disease.

    PubMed

    Temmerman, Frederik; Ho, Thien Ahn; Vanslembrouck, Ragna; Coudyzer, Walter; Billen, Jaak; Dobbels, Fabienne; van Pelt, Jos; Bammens, Bert; Pirson, Yves; Nevens, Frederik

    2015-12-01

    Polycystic liver disease (PCLD) can induce malnutrition owing to extensive hepatomegaly and patients might require liver transplantation. Six months of treatment with the somatostatin analogue lanreotide (120 mg) reduces liver volume. We investigated the efficacy of a lower dose of lanreotide and its effects on nutritional status. We performed an 18-month prospective study at 2 tertiary medical centers in Belgium from January 2011 through August 2012. Fifty-nine patients with symptomatic PCLD were given lanreotide (90 mg, every 4 weeks) for 6 months. Patients with reductions in liver volume of more than 100 mL (responders, primary end point) continued to receive lanreotide (90 mg) for an additional year (18 months total). Nonresponders were offered increased doses, up to 120 mg lanreotide, until 18 months. Liver volume and body composition were measured by computed tomography at baseline and at months 6 and 18. Patients also were assessed by the PCLD-specific complaint assessment at these time points. Fifty-three patients completed the study; 21 patients (40%) were responders. Nineteen of the responders (90%) continued as responders until 18 months. At this time point, they had a mean reduction in absolute liver volume of 430 ± 92 mL. In nonresponders (n = 32), liver volume increased by a mean volume of 120 ± 42 mL at 6 months. However, no further increase was observed after dose escalation in the 24 patients who continued to the 18-month end point. All subjects had decreased scores on all subscales of the PCLD-specific complaint assessment, including better food intake (P = .04). Subjects did not have a mean change in subcutaneous or visceral fat mass, but did have decreases in mean body weight (2 kg) and total muscle mass (1.06 cm(2)/h(2)). Subjects also had a significant mean reduction in their level of insulin-like growth factor 1, from 19% below the age-adjusted normal range level at baseline to 50% at 18 months (P = .002). In a prospective study, we

  7. Leukocyte involvement in renal reperfusion-induced liver damage.

    PubMed

    Khastar, Hossein; Kadkhodaee, Mehri; Sadeghipour, Hamid Reza; Seifi, Behjat; Hadjati, Jamshid; Delavari, Fatemeh; Soleimani, Manoocher

    2011-01-01

    Renal ischemia-reperfusion (IR) induces organ damage in remote organs. The aim of this study was to assess the role of leukocytes in the induction of liver damage after renal IR injury. Inbred mice were subjected to either sham operation or bilateral renal IR injury (60 min ischemia followed by 3 h reperfusion). Mice were then anesthetized for collection of leukocytes by heart puncture. Isolated leukocytes were transferred to two other groups: intact recipient mice that received leukocytes from IR mice and intact recipient mice that received leukocytes from sham-operated control mice. After 24 h, recipient mice were anesthetized and samples were collected. Alanine aminotransferase, aspartate aminotransferase, and hepatic malondialdehyde increased significantly, and hepatic glutathione decreased significantly in intact recipient mice that received leukocytes from IR mice in comparison with intact recipient mice that received leukocytes from sham-operated control mice. Loss of normal liver architecture, cytoplasmic vacuolization, and focal infiltration of leukocytes were seen. These results suggest that leukocytes are one of the possible factors that contribute to liver damage after renal IR injury and this damage is partly due to the induction of oxidative stress.

  8. Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans.

    PubMed

    Kantartzis, Konstantinos; Staiger, Harald; Machann, Jürgen; Schick, Fritz; Claussen, Claus D; Machicao, Fausto; Fritsche, Andreas; Häring, Hans-Ulrich; Stefan, Norbert

    2009-02-01

    We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total-, high-molecular weight (HMW)-, middle-molecular weight (MMW)-, and low-molecular weight (LMW) adiponectin were quantified by an enzyme-linked immunosorbent assay. Their relationships with liver- and intramyocellular fat, measured using (1)H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = -0.35, P = 0.012), but not with total-, MMW-, or LMW adiponectin. In addition, subjects with fatty liver (liver fat > or =5.56%, n = 15) had significantly lower HMW- (P = 0.04), but not total-, MMW-, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = -0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.

  9. Organochlorines including polychlorinated biphenyls in muscle, liver, and ovaries of cod, Gadus morhua

    SciTech Connect

    Hellou, J.; Warren, W.G.; Payne, J.F. )

    1993-11-01

    Twenty-three specific organochlorine contaminants and polychlorinated biphenyls (PCBs), measured as three Aroclor standards were analyzed in muscle, liver, and ovaries of cod, Gadus morhua, collected in the Northwest Atlantic. In general, contaminants were undetectable in muscle tissue, while concentrations were 10 times lower in ovaries than liver (wet weight). Comparison of results to other locations indicated a similarity between the ratio of the concentrations of p,p'-DDE, p,p'-DDD and p,p'-DDT, in liver of cod from the northern North Sea and from the Northwest Atlantic, although with lower levels in the present study. The ratio of alpha-HCH and gamma-HCH was between that of the central and northern North Sea. Similar ratios tend to indicate similar residence times in the atmosphere, from source to sampling area. Comparison of sigma PCB and sigma DDT in the liver of cod from various geographical locations showed the following general trend in concentrations: Arctic, Northwest Atlantic, West Atlantic, Norway < North Baltic, Nova Scotia, North Sea < South Baltic. It was observed that if the liver concentration of one compound was low (high), there was a tendency for all compounds to be low (high). Cluster analysis of organochlorines in liver pointed to the presence of four basic clusters, which could reflect similar physical chemical properties within a group. Concentrations of organochlorines in ovaries were below levels expected to affect egg and larval viability.

  10. Muscle magnetic resonance imaging in spinal muscular atrophy type 3: Selective and progressive involvement.

    PubMed

    Durmus, Hacer; Yilmaz, Ravza; Gulsen-Parman, Yesim; Oflazer-Serdaroglu, Piraye; Cuttini, Marina; Dursun, Memduh; Deymeer, Feza

    2017-05-01

    In this study we sought to identify magnetic resonance imaging (MRI) signs of selective muscle involvement and disease progression in patients with spinal muscular atrophy type 3b (SMA3b). Twenty-five patients with genetically confirmed SMA3b underwent MRI on a 1.5-Tesla MR scanner. MRI showed significantly more severe involvement of the iliopsoas than of the gluteus maximus muscles, and more severe involvement of the triceps brachii than of the biceps brachii muscles. The quadriceps femoris muscles were severely involved. The deltoid, adductor longus, portions of the hamstrings, gracilis, sartorius, and rectus abdominis muscles were well preserved. We found a significant positive correlation between MRI changes and disease duration for gluteus maximus and triceps brachii. Follow-up MRIs of 4 patients showed disease progression. This study confirms the pattern of selective muscle involvement suggested by previous studies and further refines muscle MRI changes in SMA3b. Progressive muscle involvement is implicated. Muscle Nerve 55: 651-656, 2017. © 2016 Wiley Periodicals, Inc.

  11. Effects of transcutaneous electrical stimulation of lower limb muscles on experimental fatty liver.

    PubMed

    El-Kafoury, Bataa M; Seif, Ansam A; El-Aziz Abd El-Hady, Enas A; El-Sebaiee, Ahmed E

    2016-03-01

    Although the beneficial effects of exercise on fatty liver have been described, a previous study conducted at our department showed that transcutaneous electrical muscle stimulation (TEMS) of lower abdominal muscles aggravated fatty liver. The present study aims to evaluate the ability of TEMS of the lower limb muscles to improve fatty liver infiltration. Thirty male Wistar rats were randomly allocated into three groups: control; fructose-fed (F), fed fructose-enriched diet for 6weeks; and fructose-fed with transcutaneous electrical muscle stimulation (F+TEMS), fed fructose-enriched diet for 6weeks and lower limb muscles subjected to TEMS during the last 3weeks of feeding, five sessions/week. Body weight, length, body mass index (BMI), and abdominal and lower limb circumferences were all recorded. Fasting blood glucose, serum insulin, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, serum albumin, high density lipoprotein cholesterol (HDL-C), triglyceride (TG), and total cholesterol (TC) levels were measured. LDL cholesterol (LDL-C) and the atherogenic index (AI) were calculated. Absolute and relative hepatic weights as well as histological examination of the liver were assessed. Final body weight, abdominal and lower limb circumferences, absolute liver weight, homoeostasis model assessment (HOMA) score, and TG, LDL-C, AI, serum ALT, and AST levels were all significantly reduced in the (F+TEMS) group compared to the (F) group. There was a significant increase in GPx and HDL-C levels, HDL/LDL ratio, and total protein and serum albumin content in (F+TEMS) rats compared to (F) rats. Histologically, hepatic tissue from (F+TEMS) rats had minimal steatotic changes that were restricted to zone 1 and less marked inflammatory cell infiltration compared to (F) rats. TEMS was able to reverse steatosis, hyperglycaemia, insulin resistance, dyslipidaemia, and fatty liver caused by fructose feeding. The study confirmed that the variation in

  12. Liver, spleen, pancreas and kidney involvement by human fascioliasis: imaging findings

    PubMed Central

    Zali, Mohammad Reza; Ghaziani, Tahereh; Shahraz, Saeed; Hekmatdoost, Azita; Radmehr, Ali

    2004-01-01

    Background Fasciola hepatica primarily involves the liver, however in some exceptional situations other organs have been reported to be involved. The ectopic involvement is either a result of Parasite migration or perhaps eosinophilic reaction. Case presentation Here we report a known case of multiple myeloma who was under treatment with prednisolone and melphalan. He was infected by Fasciola hepatica, which involved many organs and the lesions were mistaken with metastatic ones. Discussion Presented here is a very unusual case of the disease, likely the first case involving the pancreas, spleen, and kidney, as well as the liver. PMID:15294025

  13. Multicystic mesothelioma of the liver with secondary involvement of peritoneum and inguinal region.

    PubMed

    Di Blasi, Arturo; Boscaino, Amedeo; De Dominicis, Gianfranco; Marsilia, Giuseppina Marino; D'Antonio, Antonio; Nappi, Oscar

    2004-01-01

    A case of multicystic mesothelioma of the liver with secondary involvement of the pelvic peritoneum and the inguinal region is presented. The case is of interest because of its unusual location and peculiar biological behavior.

  14. Endocannabinoids and liver disease. IV. Endocannabinoid involvement in obesity and hepatic steatosis.

    PubMed

    Kunos, George; Osei-Hyiaman, Douglas

    2008-05-01

    Endocannabinoids are endogenous lipid mediators that interact with the same receptors as plant-derived cannabinoids to produce similar biological effects. The well-known appetitive effect of smoking marijuana has prompted inquiries into the possible role of endocannabinoids in the control of food intake and body weight. This brief review surveys recent evidence that endocannabinoids and their receptors are involved at multiple levels in the control of energy homeostasis. Endocannabinoids are orexigenic mediators and are part of the leptin-regulated central neural circuitry that controls energy intake. In addition, they act at multiple peripheral sites including adipose tissue, liver, and skeletal muscle to promote lipogenesis and limit fat elimination. Their complex actions could be viewed as anabolic, increasing energy intake and storage and decreasing energy expenditure, as components of an evolutionarily conserved system that has insured survival under conditions of starvation. In the era of plentiful food and limited physical activity, pharmacological inhibition of endocannabinoid activity offers benefits in the treatment of obesity and its hormonal/metabolic consequences.

  15. Muscle Sympathetic Nerve Activity Is Associated with Liver Insulin Sensitivity in Obese Non-Diabetic Men

    PubMed Central

    Chen, Daniel L. T.; Brown, Rachael; Liess, Carsten; Poljak, Anne; Xu, Aimin; Zhang, Jialiang; Trenell, Michael; Jenkins, Arthur; Chisholm, Donald; Samocha-Bonet, Dorit; Macefield, Vaughan G.; Greenfield, Jerry R.

    2017-01-01

    Introduction: Muscle sympathetic nerve activity (MSNA) may play a role in insulin resistance in obesity. However, the direction and nature of the relationship between MSNA and insulin resistance in obesity remain unclear. We hypothesized that resting MSNA would correlate inversely with both muscle and liver insulin sensitivity and that it would be higher in insulin-resistant vs. insulin-sensitive subjects. Materials and methods: Forty-five non-diabetic obese subjects were studied. As no significant relationships were found in women, the data presented in on 22 men aged 48 ± 12 years. Two-step (15 and 80 mU/m2/min) hyperinsulinaemic-euglycaemic clamps were performed using deuterated glucose to determine liver and muscle insulin sensitivity. Clinical and metabolic parameters were assessed. MSNA was measured via a microelectrode inserted percutaneously into the common peroneal nerve. Results: MSNA burst frequency correlated inversely with liver insulin sensitivity (r = −0.53, P = 0.02) and positively with the hepatokines C-reactive protein (CRP) and fibroblast growth factor (FGF)-19 (r = 0.57, P = 0.006, and r = −0.47, P = 0.03, respectively). MSNA burst frequency was lower in Liversen compared to Liverres (27 ± 5 vs. 38 ± 2 bursts per minute; P = 0.03). Muscle insulin sensitivity was unrelated to MSNA. Discussion: Sympathetic neural activation is related to liver insulin sensitivity and circulating hepatokines CRP and FGF-19 in non-diabetic obese men. These results suggest a potential hepato-endocrine-autonomic axis. Future studies are needed to clarify the influence of MSNA on liver insulin sensitivity in men. PMID:28293196

  16. Muscle Sympathetic Nerve Activity Is Associated with Liver Insulin Sensitivity in Obese Non-Diabetic Men.

    PubMed

    Chen, Daniel L T; Brown, Rachael; Liess, Carsten; Poljak, Anne; Xu, Aimin; Zhang, Jialiang; Trenell, Michael; Jenkins, Arthur; Chisholm, Donald; Samocha-Bonet, Dorit; Macefield, Vaughan G; Greenfield, Jerry R

    2017-01-01

    Introduction: Muscle sympathetic nerve activity (MSNA) may play a role in insulin resistance in obesity. However, the direction and nature of the relationship between MSNA and insulin resistance in obesity remain unclear. We hypothesized that resting MSNA would correlate inversely with both muscle and liver insulin sensitivity and that it would be higher in insulin-resistant vs. insulin-sensitive subjects. Materials and methods: Forty-five non-diabetic obese subjects were studied. As no significant relationships were found in women, the data presented in on 22 men aged 48 ± 12 years. Two-step (15 and 80 mU/m(2)/min) hyperinsulinaemic-euglycaemic clamps were performed using deuterated glucose to determine liver and muscle insulin sensitivity. Clinical and metabolic parameters were assessed. MSNA was measured via a microelectrode inserted percutaneously into the common peroneal nerve. Results: MSNA burst frequency correlated inversely with liver insulin sensitivity (r = -0.53, P = 0.02) and positively with the hepatokines C-reactive protein (CRP) and fibroblast growth factor (FGF)-19 (r = 0.57, P = 0.006, and r = -0.47, P = 0.03, respectively). MSNA burst frequency was lower in Liversen compared to Liverres (27 ± 5 vs. 38 ± 2 bursts per minute; P = 0.03). Muscle insulin sensitivity was unrelated to MSNA. Discussion: Sympathetic neural activation is related to liver insulin sensitivity and circulating hepatokines CRP and FGF-19 in non-diabetic obese men. These results suggest a potential hepato-endocrine-autonomic axis. Future studies are needed to clarify the influence of MSNA on liver insulin sensitivity in men.

  17. Divergent Roles of IRS (Insulin Receptor Substrate) 1 and 2 in Liver and Skeletal Muscle.

    PubMed

    Eckstein, Sabine Sarah; Weigert, Cora; Lehmann, Rainer

    2017-01-01

    IRS1 and IRS2 are the most important representatives of the IRS protein family and critical nodes in insulin/IGF1-signaling. Although they are quite similar in their structural and functional features they show tissue-specific differences. In this review, we outline the functions of IRS1 and IRS2 in skeletal muscle and liver with regard to their importance for metabolism, growth and differentiation. Mechanisms contributing to IRS1 and IRS2 dysregulation in disease states as well as consequences thereof are discussed. IRS1 plays the dominant role in skeletal muscle. It is crucial for normal growth and differentiation of myofibers, insulin-dependent glucose uptake and glycogen synthesis. The presence of IRS2 in skeletal muscle is negligible for insulin-induced glucose uptake and the general role of IRS2 in muscle is still not fully understood. In liver IRS1 and IRS2 are important to mediate insulindependent regulation of glucose and lipid metabolism and complement each other in the diurnal regulation thereof. IRS1 in the liver is more important for signaling in the late refeeding period, whereas IRS2 signaling is mostly dominating in the period directly after food intake and during fasting. Importantly, the expression level of IRS1 and IRS2 is different within the liver lobule, which could be an explanation for the phenomenon of selective insulin resistance. Dysregulated muscular or hepatic abundance and/or phosphorylation status of IRS1 and IRS2 are important factors in the pathogenesis of insulin resistance, type 2 diabetes and muscle wasting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Butyltins in muscle and liver of fish collected from certain Asian and Oceanian countries.

    PubMed

    Kannan, K; Tanabe, S; Iwata, H; Tatsukawa, R

    1995-01-01

    Concentrations of butyltin residues were determined in muscle tissue of fish collected from local markets and sea food shops in India, Bangladesh, Thailand, Indonesia, Vietnam, Taiwan, Australia, Papua New Guinea and the Solomon Islands. Contamination levels were determined in the Asia-Pacific region and human exposure was estimated. Similarly, corresponding liver samples of fish muscle collected in Australia, Papua New Guinea and the Solomon Islands were analyzed to obtain information on partitioning of butyltin compounds between muscle and liver tissues. Butyltin compounds were detected in most of the samples which suggested widespread contamination in Asia and Oceania. The concentrations of butyltin compounds were, on average, an order of magnitude higher in liver than in muscle. Residue concentration of Sigmabutyltin in liver was found to be correlated significantly (p < 0.02) with those in muscle. Intensive ship-scrapping activities, sewage disposal and antifouling paints are considered the major sources of butyltins in this region. Increased proportions of MBT over DBT and TBT in samples from most locations indicated degradation of TBT to MBT in fish tissues during storage at 4 degrees C in the dark over 1-2 years. The possibility that fish have been subject to increased exposure to MBT and that TBT degrades to MBT quite rapidly in tropical environments are also considered. Butyltin concentrations in fish from Asia and Oceania were lower than those reported for Japan, Canada and the USA. Although the number of samples analyzed from each country was small, it is tentatively suggested that intake of butyltins by humans via consumption of fish in these countries was < 25% of the tolerable daily intake of 250 ng kg bw(-1) day(-1). To our knowledge, this is the first study reporting on butyltin pollution in developing Asian countries.

  19. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs.

    PubMed

    Tous, N; Theil, P K; Lauridsen, C; Lizardo, R; Vilà, B; Esteve-Garcia, E

    2012-12-01

    The aim of this study was to investigate underlying mechanisms of dietary conjugated linoleic acid (CLA) on lipid metabolism in various tissues of pigs. Sixteen gilts (73 ± 3 kg) were fed a control (containing sunflower oil) or an experimental diet in which 4% of sunflower oil was replaced by CLA, and slaughtered at an average BW of 117 ± 4.9 kg. Transcription of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP1), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P < 0.05), whereas CLA reduced PPARα transcription in all tissues studied (P < 0.05) with the exception of intermuscular fat. Transcription of genes related to FA synthesis was reduced by CLA in SM muscle and liver (SREBP1, both P < 0.1; ACC, P < 0.01 in SM; and FAS, P < 0.01 in liver), whereas CLA reduced (P < 0.05) LPL and D6D transcriptions in SM muscle and reduced (P < 0.05) SCD in liver but increased (P < 0.05) SCD in LT muscle and intermuscular fat. Saturated FA were increased in all studied tissues (P < 0.01), while monosaturated and polyunsaturated FA were reduced in a tissue-specific way by CLA. It was concluded that dietary CLA affected transcription of genes and fat metabolism in a tissue-specific manner.

  20. Identification of a novel glycoprotein (AGp110) involved in interactions of rat liver parenchymal cells with fibronectin

    PubMed Central

    1990-01-01

    We have identified an integral membrane glycoprotein in rat liver that mediates adhesion of cultured hepatocytes on fibronectin substrata. The protein was isolated by affinity chromatography of detergent extracts on wheat germ lectin-Agarose followed by chromatography of the WGA binding fraction on fibronectin-Sepharose. The glycoprotein (AGp110), eluted at high salt concentrations from the fibronectin column, has a molecular mass of 110 kD and a pI of 4.2. Binding of immobilized AGp110 to soluble rat plasma fibronectin required Ca2+ ions but was not inhibited by RGD peptides. Fab' fragments of immunoglobulins raised in rabbits against AGp110 reversed the spreading of primary hepatocytes attached onto fibronectin-coated substrata, but had no effect on cells spread on type IV collagen or laminin substrata. The effect of the antiserum on cell spreading was reversible. AGp110 was detected by immunofluorescence around the periphery of the ventral surface of substratum attached hepatocytes, and scattered on the dorsal surface. Immunohistochemical evidence and Western blotting of fractionated liver plasma membranes indicated a bile canalicular (apical) localization of AGp110 in the liver parenchyma. Expression of AGp110 is tissue specific: it was found mainly in liver, kidney, pancreas, and small intestine but was not detected in stomach, skeletal muscle, heart, and large intestine. AGp110 could be labeled by lactoperoxidase-catalyzed surface iodination of intact liver cells and, after phase partitioning of liver plasma membranes with the detergent Triton X-114, it was preferentially distributed in the hydrophobic phase. Treatment with glycosidases indicated extensive sialic acid substitution in at least 10 O-linked carbohydrate chains and 1-2 N-linked glycans. Immunological comparisons suggest that AGp110, the integrin fibronectin receptor and dipeptidyl peptidase IV, an enzyme involved in fibronectin-mediated adhesion of hepatocytes on collagen, are distinct proteins

  1. The role of skeletal muscle in liver glutathione metabolism during acetaminophen overdose.

    PubMed

    Bilinsky, L M; Reed, M C; Nijhout, H F

    2015-07-07

    Marked alterations in systemic glutamate-glutamine metabolism characterize the catabolic state, in which there is an increased breakdown and decreased synthesis of skeletal muscle protein. Among these alterations are a greatly increased net release of glutamine (Gln) from skeletal muscle into blood plasma and a dramatic depletion of intramuscular Gln. Understanding the catabolic state is important because a number of pathological conditions with very different etiologies are characterized by its presence; these include major surgery, sepsis, trauma, and some cancers. Acetaminophen (APAP) overdose is also accompanied by dramatic changes in systemic glutamate-glutamine metabolism including large drops in liver glutathione (for which glutamate is a precursor) and plasma Gln. We have constructed a mathematical model of glutamate and glutamine metabolism in rat which includes liver, blood plasma and skeletal muscle. We show that for the normal rat, the model solutions fit experimental data including the diurnal variation in liver glutathione (GSH). We show that for the rat chronically dosed with dexamethasone (an artificial glucocorticoid which induces a catabolic state) the model can be used to explain empirically observed facts such as the linear decline in intramuscular Gln and the drop in plasma glutamine. We show that for the Wistar rat undergoing APAP overdose the model reproduces the experimentally observed rebound of liver GSH to normal levels by the 24-h mark. We show that this rebound is achieved in part by the action of the cystine-glutamate antiporter, an amino acid transporter not normally expressed in liver but induced under conditions of oxidative stress. Finally, we explain why supplementation with Gln, a Glu precursor, assists in the preservation of liver GSH during APAP overdose despite the fact that under normal conditions only Cys is rate-limiting for GSH formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Skeletal muscle involvement in falciparum malaria: biochemical and ultrastructural study.

    PubMed

    Davis, T M; Pongponratan, E; Supanaranond, W; Pukrittayakamee, S; Helliwell, T; Holloway, P; White, N J

    1999-10-01

    Biochemical evidence of skeletal muscle damage is common in malaria, but rhabdomyolysis appears to be rare. To investigate the relationship between serum creatine kinase and myoglobin levels, muscle histology, and renal function in Plasmodium falciparum infections, we studied 13 patients with uncomplicated malaria, 13 with severe noncerebral malaria, and 10 with cerebral malaria. A muscle biopsy specimen was obtained from each patient for light microscopy and electron microscopy. Mean serum creatine kinase concentrations +/- SD were raised but similar for the three groups (258 +/- 277, 149 +/- 158, and 203 +/- 197 U/L, respectively; P = .5). The mean serum myoglobin level +/- SD was highest in cerebral malaria (457 +/- 246 vs. 170 +/- 150 and 209 +/- 125 ng/mL in uncomplicated and severe malaria, respectively; P < .01) and correlated with the mean serum creatinine level (r = .39 for 36 patients; P = .02). The number of intravascular parasites, proportion of mature forms, and glycogen depletion were highest in biopsy specimens from patients with cerebral malaria. Myonecrosis was not observed. Muscle appears to be an important site for P. falciparum sequestration, which could contribute to metabolic and renal complications.

  3. Patterns of arm muscle activation involved in octopus reaching movements.

    PubMed

    Gutfreund, Y; Flash, T; Fiorito, G; Hochner, B

    1998-08-01

    The extreme flexibility of the octopus arm allows it to perform many different movements, yet octopuses reach toward a target in a stereotyped manner using a basic invariant motor structure: a bend traveling from the base of the arm toward the tip (Gutfreund et al., 1996a). To study the neuronal control of these movements, arm muscle activation [electromyogram (EMG)] was measured together with the kinematics of reaching movements. The traveling bend is associated with a propagating wave of muscle activation, with maximal muscle activation slightly preceding the traveling bend. Tonic activation was occasionally maintained afterward. Correlation of the EMG signals with the kinematic variables (velocities and accelerations) reveals that a significant part of the kinematic variability can be explained by the level of muscle activation. Furthermore, the EMG level measured during the initial stages of movement predicts the peak velocity attained toward the end of the reaching movement. These results suggest that feed-forward motor commands play an important role in the control of movement velocity and that simple adjustment of the excitation levels at the initial stages of the movement can set the velocity profile of the whole movement. A simple model of octopus arm extension is proposed in which the driving force is set initially and is then decreased in proportion to arm diameter at the bend. The model qualitatively reproduces the typical velocity profiles of octopus reaching movements, suggesting a simple control mechanism for bend propagation in the octopus arm.

  4. Involvement of the muscle-tendon junction in skeletal muscle atrophy: an ultrastructural study.

    PubMed

    de Palma, L; Marinelli, M; Pavan, M; Bertoni-Freddari, C

    2011-01-01

    The muscle-tendon junction (MTJ) is a physiologically vital tissue interface and a highly specialized region in the muscle-tendon unit. It is the weakest point in the muscle-tendon unit, making it susceptible to strain injuries. Nonetheless, knowledge of the pathological changes affecting this region and of its response to the atrophy process is very limited. The aim of the study was to examine MTJ ultrastructural morphology in patients with different conditions that induce skeletal muscle atrophy and to attempt a grading of the atrophy process. Fifteen patients undergoing amputation in the distal or proximal third of the lower leg due to chronic or acute conditions were divided into two groups. Specimens of gastrocnemius muscle collected at the time of surgery were analyzed by histology and electron microscopy. The contact between muscle and tendon was measured using a dedicated software that calculated semi-automatically the base (B) and perimeter (P) of muscle cell finger-like processes at the MTJ. Electron microscopy. The cells in the atrophic muscle of the chronic group were shallow and bulky. In the acute group, the myotendinous endings differed significantly in their structure from those of the chronic group. In atrophic muscle, the contact between muscle and tendon was reduced by quantitative and qualitative changes in the myotendinous endings. The B/P ratio allowed definition of three grades of myotendinous ending degeneration. It is unclear whether degenerative changes induced by immobilization in muscle and, specifically, the MTJ are temporary and reversible or permanent. This preliminary study suggested a classification of ultrastructural MTJ changes into grade 0, reflecting a quite normal MTJ; grade 1, an intermediate process that might lead to irreversible atrophy or to recovery, spontaneously or with drug therapy; and grade 2, irreversible process with complete structural alteration.

  5. Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk

    PubMed Central

    Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

    2016-01-01

    Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production

  6. Paraoxonase 1 and dietary hyperhomocysteinemia modulate the expression of mouse proteins involved in liver homeostasis.

    PubMed

    Suszyńska-Zajczyk, Joanna; Jakubowski, Hieronim

    2014-01-01

    Homocysteine (Hcy), a product of methionine metabolism, is elevated by the consumption of a high-methionine diet that can cause fatty liver disease. Paraoxonase 1 (Pon1), a hydrolase expressed mainly in the liver and carried in the circulation on high-density lipoprotein, participates in Hcy metabolism. Low Pon1 activity is linked to fatty liver disease. We hypothesize that hyperhomocysteinemia and low Pon1 induce changes in gene expression that could impair liver homeostasis. To test this hypothesis, we analyzed the liver proteome of Pon1(-/-) and Pon1(+/+) mice fed a high methionine diet (1% methionine in the drinking water) for 8 weeks using 2D IEF/SDS-PAGE gel electrophoresis and MALDI-TOF mass spectrometry. We identified seven liver proteins whose expression was significantly altered in Pon1(-/-) mice. In animals fed with a control diet, the expression of three liver proteins involved in lipoprotein metabolism (ApoE), iron metabolism (Ftl), and regulation of nitric oxide generation (Ddah1) was up-regulated by the Pon1(-/-) genotype. In mice fed with a high-methionine diet, expression of four liver proteins was up-regulated and of three proteins was down-regulated by the Pon1(-/-) genotype. The up-regulated proteins are involved in lipoprotein metabolism (ApoE), energy metabolism (Atp5h), oxidative stress response (Prdx2), and nitric oxide regulation (Ddah1). The down-regulated proteins are involved in energy metabolism (Gamt), iron metabolism (Ftl), and catechol metabolism (Comt). Expression of one protein (Ftl) was up-regulated both by the Pon1(-/-) genotype and a high-methionine diet. Our findings suggest that Pon1 interacts with diverse cellular processes - from lipoprotein metabolism, nitric oxide regulation, and energy metabolism to iron transport and antioxidant defenses - that are essential for normal liver homeostasis and modulation of these interactions by a high-methionine diet may contribute to fatty liver disease.

  7. Microtubule motors involved in nuclear movement during skeletal muscle differentiation.

    PubMed

    Gache, V; Gomes, E R; Cadot, B

    2017-04-01

    Nuclear positioning is a determining event in several cellular processes, such as fertilization, cell migration, and cell differentiation. The structure and function of muscle cells, which contain hundreds of nuclei, have been shown to rely in part on proper nuclear positioning. Remarkably, in the course of muscle differentiation, nuclear movements along the myotube axis might represent the event required for the even positioning of nuclei in the mature myofiber. Here we analyze nuclear behavior, time in motion, speed, and alignment during myotube differentiation and temporal interference of cytoskeletal microtubule-related motors. Using specific inhibitors, we find that nuclear movement and alignment are microtubule dependent, with 19 microtubule motor proteins implicated in at least one nuclear behavior. We further focus on Kif1c, Kif5b, kif9, kif21b, and Kif1a, which affect nuclear alignment. These results emphasize the different roles of molecular motors in particular mechanisms.

  8. Free amino acids in plasma and skeletal muscle of patients with liver cirrhosis.

    PubMed

    Montanari, A; Simoni, I; Vallisa, D; Trifirò, A; Colla, R; Abbiati, R; Borghi, L; Novarini, A

    1988-01-01

    Free amino acids were measured under postabsorptive conditions in plasma and intracellular water of skeletal muscle obtained by needle biopsy in nine healthy controls and 14 subjects suffering from clinically stable liver cirrhosis. The aromatic amino acids phenylalanine and tyrosine in cirrhotics were elevated to the same extent in plasma and in muscle water. Branched-chain amino acids were uniformly reduced in plasma, but in muscle water only valine was significantly lower (222 +/- 92 mumoles per kg intracellular water vs. 368 +/- 82, p less than 0.001), while isoleucine (142 +/- 63 vs. 103 +/- 30), leucine (223 +/- 88 vs. 226 +/- 36) and branched-chain amino acids as a whole (589 +/- 186 vs. 681 +/- 88) were normal or elevated with an increased muscle:plasma ratio (3.12 +/- 2.03 vs. 1.41 +/- 0.37, p less than 0.05 for isoleucine; 3.00 +/- 1.28 vs. 1.85 +/- 0.27, p less than 0.025 for leucine; 2.24 +/- 0.64 vs. 1.69 +/- 0.13, p less than 0.05 for total branched-chain amino acids. Our data show that, in cirrhosis, plasma concentrations of branched-chain amino acids do not reflect their levels in muscle cellular water; only the intracellular pool of valine is severely depleted. This suggests that higher amounts of valine supplementation may be useful in nutritional treatment of liver cirrhosis. The elevated muscle:plasma gradients for branched-chain amino acids may result from abnormalities in their transport through muscle-plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Partial hepatectomy-induced regeneration accelerates reversion of liver fibrosis involving participation of hepatic stellate cells.

    PubMed

    Suárez-Cuenca, Juan A; Chagoya de Sánchez, Victoria; Aranda-Fraustro, Alberto; Sánchez-Sevilla, Lourdes; Martínez-Pérez, Lidia; Hernández-Muñoz, Rolando

    2008-07-01

    Hepatic fibrosis underlies most types of chronic liver diseases and is characterized by excessive deposition of extracellular matrix (ECM), altered liver architecture, and impaired hepatocyte proliferation; however, the fibrotic liver can still regenerate after partial hepatectomy (PH). Therefore, the present study was aimed at addressing whether a PH-induced regeneration normalizes ECM turnover and the possible involvement of hepatic stellate cells (HSC) during resolution of a pre-established fibrosis. Male Wistar rats were rendered fibrotic by intraperitoneal administration of swine serum for 9 weeks and subjected afterwards to 70% PH or sham-operation. Histological and morphometric analyses were performed, and parameters indicative of cell proliferation, collagen synthesis and degradation, and activation of HSC were determined. Liver collagen content was reduced to 75% after PH in cirrhotic rats when compared with sham-operated cirrhotic rats. The regenerating fibrotic liver oxidized actively free proline and had diminished transcripts for alpha-1 (I) collagen mRNA, resulting in decreased collagen synthesis. PH also increased collagenase activity, accounted for by higher amounts of pro-MMP-9, MMP-2, and MMP-13, which largely coincided with a lower expression of TIMP-1 and TIMP-2. Therefore, an early decreased collagen synthesis, mild ECM degradation, and active liver regeneration were followed by higher collagenolysis and limited deposition of ECM, probably associated with increased mitochondrial activity. Activated HSC readily increased during liver fibrosis and remained activated after liver regeneration, even during fibrosis resolution. In conclusion, stimulation of liver regeneration through PH restores the balance in ECM synthesis/degradation, leading to ECM remodeling and to an almost complete resolution of liver fibrosis. As a response to the regenerative stimulus, activated HSC seem to play a controlling role on ECM remodeling during experimental

  10. Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines.

    PubMed

    Sagarkar, Sneha; Gandhi, Deepa; Devi, S Saravana; Sakharkar, Amul; Kapley, Atya

    2016-01-01

    Chronic exposure to atrazine and other pesticides is reported to cause metabolic disorders, yet information on effects of atrazine on expression of genes relevant to mitochondrial function is largely missing. In the present study, therefore, we investigated the expression of a battery of nuclear- and mitochondrial-encoded genes involved in oxidative phosphorylation (OXPHOS) in human liver (HepG2) and rat muscle (L6) cell lines due to short-term atrazine exposure. We have determined the EC50 values of atrazine for cytotoxicity and mitochondrial toxicity (mitotoxicity) in terms of adenosine triphosphate (ATP) content in HepG2 and L6 cells. Further, the mRNA expression of nuclear- and mitochondrial-encoded genes was analyzed using quantitative real-time polymerase chain reaction. The EC50 value of atrazine for mitotoxicity in HepG2 and L6 cells was found to be about 0.162 and 0.089 mM, respectively. Mitochondrial toxicity was indicated by reduction in ATP content following atrazine exposure. Atrazine exposure resulted in down-regulation of many OXPHOS subunits expression and affected biogenesis factors' expression. Most prominently, superoxide dismutase (SOD) and sirtuin 3 (SIRT3) expressions were up-regulated in HepG2 cells, whereas SIRT3 expression was alleviated in L6 cells, without significant changes in SOD levels. Mitochondrial transcription factor A (TFAM) and SIRT1 expression were significantly down-regulated in both cell lines. Results suggest that TFAM and SIRT1 could be involved in atrazine-induced mitochondrial dysfunction, and further studies can be taken up to understand the mechanism of mitochondrial toxicity. Further study can also be taken up to explore the possibility of target genes as biomarkers of pesticide toxicity.

  11. Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines

    PubMed Central

    Sagarkar, Sneha; Gandhi, Deepa; Devi, S. Saravana; Sakharkar, Amul; Kapley, Atya

    2016-01-01

    Objective: Chronic exposure to atrazine and other pesticides is reported to cause metabolic disorders, yet information on effects of atrazine on expression of genes relevant to mitochondrial function is largely missing. In the present study, therefore, we investigated the expression of a battery of nuclear- and mitochondrial-encoded genes involved in oxidative phosphorylation (OXPHOS) in human liver (HepG2) and rat muscle (L6) cell lines due to short-term atrazine exposure. Materials and Methods: We have determined the EC50 values of atrazine for cytotoxicity and mitochondrial toxicity (mitotoxicity) in terms of adenosine triphosphate (ATP) content in HepG2 and L6 cells. Further, the mRNA expression of nuclear- and mitochondrial-encoded genes was analyzed using quantitative real-time polymerase chain reaction. Results: The EC50 value of atrazine for mitotoxicity in HepG2 and L6 cells was found to be about 0.162 and 0.089 mM, respectively. Mitochondrial toxicity was indicated by reduction in ATP content following atrazine exposure. Atrazine exposure resulted in down-regulation of many OXPHOS subunits expression and affected biogenesis factors’ expression. Most prominently, superoxide dismutase (SOD) and sirtuin 3 (SIRT3) expressions were up-regulated in HepG2 cells, whereas SIRT3 expression was alleviated in L6 cells, without significant changes in SOD levels. Mitochondrial transcription factor A (TFAM) and SIRT1 expression were significantly down-regulated in both cell lines. Conclusion: Results suggest that TFAM and SIRT1 could be involved in atrazine-induced mitochondrial dysfunction, and further studies can be taken up to understand the mechanism of mitochondrial toxicity. Further study can also be taken up to explore the possibility of target genes as biomarkers of pesticide toxicity. PMID:27114639

  12. Cadmium accumulation in gill, liver, kidney and muscle tissues of common carp, Cyprinus carpio, and Nile tilapia, Oreochromis niloticus.

    PubMed

    Yeşilbudak, Burcu; Erdem, Cahit

    2014-05-01

    Accumulation of cadmium in gill, liver, muscle and kidney tissues of Cyprinus carpio and Oreochromis niloticus were investigated in fish exposed to 0.5 ppm cadmium over 1, 15 and 30 days under controlled laboratory conditions. Tissue accumulation of the metal was measured using Atomic Absorption Spectrophotometric techniques. Cadmium accumulation in gill, liver, kidney and muscle, tissues of C. carpio and O. niloticus exposed to metal for 1, 15 and 30 days increased significantly compared with the control group (p < 0.05), except muscle tissue of O. niloticus. A general increase was observed in Cd accumulation with increasing exposure periods. Highest metal accumulation was observed in kidney followed by liver, gill and muscle tissues in both species. Liver accumulation of Cd was higher in C. carpio than O. niloticus, whereas kidney accumulation of the metal was higher in O. niloticus than C. carpio.

  13. Histopathological changes in liver, kidney and muscles of pesticides exposed malnourished and diabetic rats.

    PubMed

    Benjamin, Nidhi; Kushwah, Ameeta; Sharma, R K; Katiyar, A K

    2006-03-01

    Histopathological changes were observed in liver, kidney and muscles of normal, protein-malnourished, diabetic as well as both protein-malnourished and diabetic albino rats when exposed to a mixture of monocrotophos, hexachlorocyclohexane and endosulfan at varying intervals. The examination revealed hepatotoxic, nephrotoxic and muscular necrotic effects in pesticides exposed rats. Toxicity was aggravated in protein-malnourished and diabetic animals and more so, if the animals were both diabetic and protein-malnourished.

  14. Protein adduct species in muscle and liver of rats following acute ethanol administration.

    PubMed

    Patel, Vinood B; Worrall, Simon; Emery, Peter W; Preedy, Victor R

    2005-01-01

    Previous immunohistochemical studies have shown that the post-translational formation of aldehyde-protein adducts may be an important process in the aetiology of alcohol-induced muscle disease. However, other studies have shown that in a variety of tissues, alcohol induces the formation of various other adduct species, including hybrid acetaldehyde-malondialdehyde-protein adducts and adducts with free radicals themselves, e.g. hydroxyethyl radical (HER)-protein adducts. Furthermore, acetaldehyde-protein adducts may be formed in reducing or non-reducing environments resulting in distinct molecular entities, each with unique features of stability and immunogenicity. Some in vitro studies have also suggested that unreduced adducts may be converted to reduced adducts in situ. Our objective was to test the hypothesis that in muscle a variety of different adduct species are formed after acute alcohol exposure and that unreduced adducts predominate. Rabbit polyclonal antibodies were raised against unreduced and reduced aldehydes and the HER-protein adducts. These were used to assay different adduct species in soleus (type I fibre-predominant) and plantaris (type II fibre-predominant) muscles and liver in four groups of rats administered acutely with either [A] saline (control); [B] cyanamide (an aldehyde dehydrogenase inhibitor); [C] ethanol; [D] cyanamide+ethanol. Amounts of unreduced acetaldehyde and malondialdehyde adducts were increased in both muscles of alcohol-dosed rats. However there was no increase in the amounts of reduced acetaldehyde adducts, as detected by both the rabbit polyclonal antibody and the RT1.1 mouse monoclonal antibody. Furthermore, there was no detectable increase in malondialdehyde-acetaldehyde and HER-protein adducts. Similar results were obtained in the liver. Adducts formed in skeletal muscle and liver of rats exposed acutely to ethanol are mainly unreduced acetaldehyde and malondialdehyde species.

  15. Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

    PubMed Central

    Poggiogalle, Eleonora; Donini, Lorenzo Maria; Lenzi, Andrea; Chiesa, Claudio; Pacifico, Lucia

    2017-01-01

    The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle. PMID:28348479

  16. Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle.

    PubMed

    Poggiogalle, Eleonora; Donini, Lorenzo Maria; Lenzi, Andrea; Chiesa, Claudio; Pacifico, Lucia

    2017-03-14

    The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.

  17. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis

    PubMed Central

    Chackelevicius, Carla Melisa; Gambaro, Sabrina Eliana; Tiribelli, Claudio; Rosso, Natalia

    2016-01-01

    The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies. PMID:27895397

  18. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis.

    PubMed

    Chackelevicius, Carla Melisa; Gambaro, Sabrina Eliana; Tiribelli, Claudio; Rosso, Natalia

    2016-11-07

    The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies.

  19. [Perioperative management for liver transplant in a patient with familial amyloid polyneuropathy with heart involvement].

    PubMed

    López-Herrera Rodríguez, D; Guerrero Domínguez, R; Mellado Miras, P; Gómez Sosa, L

    2015-01-01

    Familial amyloid polyneuropathy (FAP) is a systemic amyloidosis caused by mutated transthyretin. Cardiac amyloidosis, the major prognostic determinant in systemic amyloidosis, is characterized by infiltration of the myocardium, leading to cardiomyopathy and conduction disturbances. Liver transplantation is the only curative option for patients with FAP. The case is presented of a 36-year-old patient with type i FAP with cardiac involvement, proposed for liver transplant surgery, which was successfully performed without any preoperative event of interest.

  20. Prelamin A is involved in early steps of muscle differentiation

    SciTech Connect

    Capanni, Cristina; Del Coco, Rosalba; Squarzoni, Stefano; Columbaro, Marta; Mattioli, Elisabetta; Rocchi, Anna; Scotlandi, Katia; Maraldi, Nadir; Foisner, Roland; Lattanzi, Giovanna

    2008-12-10

    Lamin A is a nuclear lamina constituent implicated in a number of human disorders including Emery-Dreifuss muscular dystrophy. Since increasing evidence suggests a role of the lamin A precursor in nuclear functions, we investigated the processing of prelamin A during differentiation of C2C12 mouse myoblasts. We show that both protein levels and cellular localization of prelamin A are modulated during myoblast activation. Similar changes of lamin A-binding proteins emerin and LAP2{alpha} were observed. Furthermore, prelamin A was found in a complex with LAP2{alpha} in differentiating myoblasts. Prelamin A accumulation in cycling myoblasts by expressing unprocessable mutants affected LAP2{alpha} and PCNA amount and increased caveolin 3 mRNA and protein levels, while accumulation of prelamin A in differentiated muscle cells following treatment with a farnesyl transferase inhibitor appeared to inhibit caveolin 3 expression. Our data provide evidence for a critical role of the lamin A precursor in the early steps of muscle cell differentiation.

  1. Dietary (-)-Epigallocatechin-3-gallate Supplementation Counteracts Aging-Associated Skeletal Muscle Insulin Resistance and Fatty Liver in Senescence-Accelerated Mouse.

    PubMed

    Liu, Hung-Wen; Chan, Yin-Ching; Wang, Ming-Fu; Wei, Chu-Chun; Chang, Sue-Joan

    2015-09-30

    Aging is accompanied by pathophysiological changes including insulin resistance and fatty liver. Dietary supplementation with (-)-epigallocatechin-3-gallate (EGCG) improves insulin sensitivity and attenuates fatty liver disease. We hypothesized that EGCG could effectively modulate aging-associated changes in glucose and lipid metabolism in senescence-accelerated mice (SAM) prone 8 (SAMP8). Higher levels of glucose, insulin, and free fatty acid, inhibited Akt activity, and decreased glucose transporter 4 (GLUT4) expression were observed in SAMP8 mice compared to the normal aging group, SAM resistant 1 mice. EGCG supplementation for 12 weeks successfully decreased blood glucose and insulin levels via restoring Akt activity and GLUT4 expression and stimulating AMPKα activation in skeletal muscle. EGCG up-regulated genes involved in mitochondrial biogenesis and subsequently restored mitochondrial DNA copy number in skeletal muscle of SAMP8 mice. Decreased adipose triglyceride lipase and increased sterol regulatory element binding proteins-1c (SREBP-1c) and carbohydrate responsive element binding protein at mRNA levels were observed in SAMP8 mice in accordance with hepatocellular ballooning and excess lipid accumulation. The pevention of hepatic lipid accumulation by EGCG was mainly attributed to down-regulation of mTOR and SREBP-1c-mediated lipid biosynthesis via suppression of the positive regulator, Akt, and activation of the negative regulator, AMPKα, in the liver. EGCG beneficially modulates glucose and lipid homeostasis in skeletal muscle and liver, leading to alleviation of aging-associated metabolic disorders.

  2. Studies on adenosine triphosphate transphosphorylases. Human isoenzymes of adenylate kinase: isolation and physicochemical comparison of the crystalline human ATP-AMP transphosphorylases from muscle and liver.

    PubMed

    Kuby, S A; Fleming, G; Frischat, A; Cress, M C; Hamada, M

    1983-02-10

    Procedures are described for the isolation, in crystalline form, of the adenylate kinases from autopsy samples of human muscle and from human liver. Weight average molecular weights were determined by sedimentation equilibrium to be 22,000 (+/- 700) and 25,450 (+/- 160) for the human muscle and liver isoenzymes, respectively. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, their molecular weights were estimated to be 21,700 and 26,500 for the muscle and liver enzymes, respectively. Both isoenzymes are accordingly monomeric proteins in their native state. Amino acid analyses are reported here for the normal human liver, calf liver, and rabbit liver adenylate kinases and compared with the normal human muscle, calf muscle, and rabbit muscle myokinases. The liver types as a group and the muscle types as a group show a great deal of homology, but some distinct differences are evident between the liver and muscle enzyme groups, especially in the number of residues of His, Pro, half-cystine, and the presence of tryptophan in the liver enzymes. The normal human liver adenylate kinase, as isolated in this report, has proved to be similar in its properties, if not identical, to the adenylate kinase isolated directly from human liver mitochondria (Hamada, M., Sumida, M., Okuda, H., Watanabe, T., Nojima, M., and Kuby, S. A. (1982) J. Biol. Chem. 257, 13120-13128). Therefore, the liver-type adenylate kinase may be considered a mitochondrial type.

  3. Should the involvement of skeletal muscle by prostatic adenocarcinoma be reported on biopsies?

    PubMed

    Sadimin, Evita T; Ye, Huihui; Epstein, Jonathan I

    2016-03-01

    Skeletal muscle is seen at the distal part of the prostate apex, where benign glands may reside as part of normal anatomy and histology, and extends more proximally anteriorly. At times, prostatic adenocarcinoma can be seen admixed with skeletal muscle, raising the question of extraprostatic extension. Although there has been increased attention regarding biopsy sampling of the distal apex to guide the performing of the apical dissection on radical prostatectomy, the finding of skeletal muscle involvement by prostatic adenocarcinoma has not been consistently reported by pathologists on biopsies. We searched our database spanning 12 years from 2000 to 2012 for all patients who had prostatic adenocarcinoma Gleason score 3 + 3 = 6 involving skeletal muscle on biopsy. We identified 220 patients who met the criteria. Of the 220 patients, 101 underwent prostatectomy, which comprised the "study group." Prostatectomy reports from these patients were compared with those of a "control group," which consisted of 201 contemporaneous patients with Gleason score 3 + 3 = 6 prostatic adenocarcinoma on biopsy without skeletal muscle involvement. The results showed a significantly higher percentage of positive margins in the study group compared with the control group (P = .006). The study group also had a higher percentage of positive margins at the apex admixed with skeletal muscle (P = .008). In summary, the findings in this study support that pathologists should report the involvement of skeletal muscle by tumor, and recommend that urologists performing radical prostatectomies on these patients try to ensure adequate excision in the apical area to avoid positive apical margin.

  4. [Patient of myofibrillar myopathy associated with muscle cramp and distal muscle involvement].

    PubMed

    Okada, Yoichiro; Ayaki, Takashi; Matsumoto, Riki; Ito, Hidefumi; Takahashi, Ryosuke; Nakano, Satoshi

    2012-01-01

    A 53-year-old man presented mild, but gradually worsening, distal-dominant upper bilateral limbs weakness and muscle cramp in both legs from the age of 30. He had no obvious muscle atrophy during the course of the disease. Muscle biopsy of the right lateral vastus muscle showed myopathic changes with round or helical hyaline inclusions in eosinophilic on H&E staining and dark green on modified Gomori trichrome. There were also non-rimmed vacuoles. NADH-TR showed lack of enzymic activity in areas corresponding to the inclusions. Immunohistochemistry demonstrated abnormal accumulation of desmin and myotilin in fibers with inclusions. Given these pathological findings, he was diagnosed with myofibrillar myopathy (MFM). Because MFM is genetically heterogeneous, its clinical manifestations are reported as variable. While MFM patients are sometimes reported to develop serious conditions such as severe weakness, cardiomyopathy or respiratory failure, which require a pacemaker or mechanical ventilator, our case only had mild distal dominant limb weakness and muscle cramps. Our patient suggests that we must consider MFM as a differential diagnosis in adult onset distal myopathies.

  5. Partition and metabolic fate of dietary glycerol in muscles and liver of juvenile tilapia.

    PubMed

    da Costa, Diego Vicente; Dias, Jorge; Colen, Rita; Rosa, Priscila Vieira; Engrola, Sofia

    2017-04-01

    This study investigated the effect of dietary glycerol on the metabolism of juvenile tilapia (Oreochromis mossambicus) and to determine its metabolic fate. The experimental diets contained 0% (Group CON), 5% (Group G5) and 15% glycerol (Group G15) and were fed for 40 d to apparent satiation, three times a day. For the metabolism trials, six fish from each treatment were randomly chosen and tube-fed with five pellets labelled with (14)C-glycerol [(14)C(U)] in order to evaluate the absorption, catabolism, retention and partition of glycerol in muscle and liver. Group G5 presented the highest (14)C-glycerol retention and the lowest catabolism, with no significant differences between Groups CON and G15. In Group CON, the highest percentage of (14)C was incorporated in muscle lipids; with no significant differences between Groups G5 and G15. Furthermore, no treatment effects were found for hepatic (14)C-lipid and for (14)C in hepatic and muscle non-lipid extract. In the non-lipid and non-protein fraction, the highest radioactivity was measured in livers of Group G5, however no significant differences were found for this fraction between Groups CON and G15 in liver and for all treatments in muscle. The results of the present study can have practical implications in diet formulations for tilapia and for other aquaculture species with similar feeding pattern since juvenile tilapia are able to metabolise dietary glycerol into lipids, protein and/or carbohydrates and to use it as energy source.

  6. Does high-sucrose diet alter skeletal muscle and liver mitochondrial respiration?

    PubMed

    Lambert, K; Py, G; Robert, E; Mercier, J

    2003-09-01

    A diet high in sucrose or fructose progressively impairs glucose and lipid metabolism, which leads to insulin resistance. As mitochondria are the sites of the oxidation and utilization of these substrates, we hypothesized that a high sucrose diet would alter mitochondrial respiration. Male Wistar rats were fed high-sucrose (SU) or control (CTL) diet for one week; mitochondrial respiration was investigated in mitochondria isolated from liver and both glycolytic and oxidative muscles, with pyruvate and palmitate as substrates. To test for metabolic disturbances, we measured not only glycogen content in muscles and liver, but also lactate, glucose and triglyceride blood concentrations. After one week of high-sucrose intake, we found no change in blood concentration of these variables, but glycogen content was significantly increased in liver (17.28 +/- 2.98 mg/g tissue SU vs 6.47 +/- 1.67 mg/g tissue CTL), oxidative muscle (1.59 +/- 0.21 mg/g tissue SU vs 0.70 +/- 0.24 mg/g tissue CTL) though not in glycolytic muscle (1.72 +/- 0.44 mg/g tissue SU vs 1.52 +/- 0.20 mg/g tissue CTL). State 3 mitochondrial respiration was significantly decreased in SU rats compared with CTL (p < 0.05) with pyruvate, while no change was observed with palmitate. This study shows that 1-week of high-sucrose diet altered mitochondrial pyruvate oxidation in rats and suggests that, in the context of a high-sucrose diet, impaired mitochondrial respiration could contributed to the development of insulin resistance.

  7. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    PubMed

    Kunkel, Steven D; Elmore, Christopher J; Bongers, Kale S; Ebert, Scott M; Fox, Daniel K; Dyle, Michael C; Bullard, Steven A; Adams, Christopher M

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  8. Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

    PubMed Central

    Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness. PMID:22745735

  9. Turnover of stable carbon isotopes in the muscle, liver, and breath CO2 of alpacas (Lama pacos).

    PubMed

    Sponheimer, M; Robinson, T F; Cerling, T E; Tegland, L; Roeder, B L; Ayliffe, L; Dearing, M D; Ehleringer, J R

    2006-01-01

    Stable carbon isotope analysis of animal liver and muscle has become a widespread tool for investigating dietary ecology. Nonetheless, stable carbon isotope turnover of these tissues has not been studied in large mammals except with isotopically labelled tracer methodologies, which do not produce carbon half-lives analogous to those derived from naturalistic diet-switch experiments. To address this gap, we studied turnover of carbon isotopes in the liver, muscle, and breath CO2 of alpacas (Lama pacos) by switching them from a C3 grass diet to an isonitrogenous C4 grass diet. Breath samples as well as liver and muscle biopsies were collected and analyzed for up to 72 days to monitor the incorporation of the C4-derived carbon. The data suggest half-lives of 2.8, 37.3, and 178.7 days for alpaca breath CO2, liver, and muscle, respectively. Alpaca liver and muscle carbon half-lives are about 6 times longer than those of gerbils, which is about what would be expected given their size. In contrast, breath CO2 turnover does not scale readily with body mass. We also note that the breath CO2 and liver data are better described using a multiple-pool exponential decay model than a single-pool model. Copyright 2006 John Wiley & Sons, Ltd.

  10. A Comparison of Muscle Function, Mass, and Quality in Liver Transplant Candidates: Results From the Functional Assessment in Liver Transplantation Study.

    PubMed

    Wang, Connie W; Feng, Sandy; Covinsky, Kenneth E; Hayssen, Hilary; Zhou, Li-Qin; Yeh, Benjamin M; Lai, Jennifer C

    2016-08-01

    Sarcopenia and functional impairment are common and lethal extrahepatic manifestations of cirrhosis. We aimed to determine the association between computed tomography (CT)-based measures of muscle mass and quality (sarcopenia) and performance-based measures of muscle function. Adults listed for liver transplant underwent testing of muscle function (grip strength, Short Physical Performance Battery [SPPB]) within 3 months of abdominal CT. Muscle mass (cm/m) = total cross-sectional area of psoas, paraspinal, and abdominal wall muscles at L3 on CT, normalized for height. Muscle quality = mean Hounsfield units for total skeletal muscle area at L3. Among 292 candidates, median grip strength was 31 kg, SPPB score was 11, muscle mass was 49 cm/m, and muscle quality was 35 Hounsfield units. Grip strength weakly correlated with muscle mass (ρ = 0.26, P < 0.001) and quality (ρ = 0.27, P < 0.001) in men, and muscle quality (ρ = 0.23, P = 0.02), but not muscle mass, in women. Short Physical Performance Battery correlated weakly with muscle quality in men (ρ = 0.38, P < 0.001) and women (ρ = 0.25, P = 0.02), however, did not correlate with muscle mass in men or women. After adjustment for sex, model for end-stage liver disease (MELD)-Na, hepatocellular carcinoma, and body mass index, grip strength (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59-0.92; P = 0.008), SPPB (HR, 0.89; 95% CI, 0.82-0.97; P = 0.01), and muscle quality (HR, 0.77; 95% CI, 0.63-0.95; P = 0.02) were associated with waitlist mortality, but muscle mass was not (HR, 0.91; 95% CI, 0.75-1.11; P = 0.35). Performance-based tests of muscle function are only modestly associated with CT-based muscle measures. Given that they predict waitlist mortality and can be conducted quickly and economically, tests of muscle function may have greater clinical utility than CT-based measures of sarcopenia.

  11. Mercury concentrations in gonad, liver, and muscle of white sturgeon Acipenser transmontanus in the lower Columbia River.

    PubMed

    Webb, M A H; Feist, G W; Fitzpatrick, M S; Foster, E P; Schreck, C B; Plumlee, M; Wong, C; Gundersen, D T

    2006-04-01

    This study determined the partitioning of total mercury in liver, gonad, and cheek muscle of white sturgeon (Acipenser transmonatus) in the lower Columbia River. The relationship between tissue mercury concentrations and various physiologic parameters was assessed. White sturgeon were captured in commercial fisheries in the estuary and Bonneville, The Dalles, and John Day Reservoirs. Condition factor (CF), relative weight (Wr), and gonadosomatic index (GSI) were determined for each fish (n = 57). Gonadal tissue was examined histologically to determine sex and stage of maturity. Liver (n = 49), gonad (n = 49), and cheek muscle (n = 57) were analyzed for total mercury using cold-vapor atomic fluorescence spectrophotometry. Tissue protein concentrations were measured by ultraviolet-visible spectroscopy. Plasma was analyzed for testosterone (T), 11-ketotestosterone (KT), and 17ss-estradiol (E2) using radioimmunoassay. Mean tissue mercury concentrations were higher in muscle compared with liver and gonad at all sampling locations, except Bonneville Reservoir where mean liver mercury content was the highest tissue concentration observed in the study. Significant negative correlations between plasma androgens (T and KT) and muscle mercury content and plasma E2 and liver mercury content were found. A significant positive linear relationship between white sturgeon age and liver mercury concentrations was evident. Significant negative correlations between CF and relative weight and gonad and liver mercury content were found. In addition, immature male sturgeon with increased gonad mercury content had decreased GSIs. These results suggest that mercury, in the form of methylmercury, may have an effect on the reproductive potential of white sturgeon.

  12. Biomonitoring of trace elements in muscle and liver tissue of freshwater fish

    NASA Astrophysics Data System (ADS)

    Wagner, Annemarie; Boman, Johan

    2003-12-01

    The aim of this study was to investigate the potential impact of a coal combustion power plant in the northern part of Vietnam with regard to elemental pollution on the surrounding environment. Freshwater fishes ( Clarias fucus) were sampled both at a site exposed to the emissions of the power plant and at a reference site seemingly free from industrial activities. The elemental concentrations in muscle and liver tissue were analyzed using total-reflection X-ray fluorescence and atomic absorption spectroscopy. A comparison of muscle tissue with International Standards (Food and Agricultural Organization) showed that the fishes from both sites did not constitute any health risk for human consumers with regard to the elements Cu, Zn, As, Se, Cd, Pb and Cr. Generally, concentration differences between sites were found to be small in the edible tissue. Compared to the muscle tissue, concentrations of metals were elevated in the liver. The elemental concentrations of P, S, K, Ca, Fe, Mn, Zn and Pb were significantly higher in the hepatic tissue from the exposed site, suggesting—together with measurements of airborne pollutants—emissions from the power plant as a probable source of these elements.

  13. Evaluating glycogen signal contamination in muscle by (13)C MRS of the liver.

    PubMed

    Tomiyasu, Moyoko; Obata, Takayuki; Nonaka, Hiroi; Nishi, Yukio; Nakamoto, Hiromitsu; Takayama, Yukihisa; Ikehira, Hiroo; Kanno, Iwao

    2008-05-01

    To evaluate the contamination of glycogen signal synthesized in skeletal muscle by that in the liver, long-term monitoring of over 7 h of in vivo [1-(13)C] glycogen synthesis/degradation at the right abdomen and left shoulder was achieved using a 3.0-T clinical MR system. (13)C MR spectra without localization were obtained from five healthy volunteers before and after oral administration of 85 g of d-glucose, including 10 g of 99% [1-(13)C] glucose. In all volunteers, the relative signal intensities at the abdomen to those at shoulder were about two- to fivefold, and those of time-course changes at the abdomen and shoulder were dissimilar. It is considered that the quantity of muscle-synthesized glycogen signal at the abdomen is less than that at the shoulder because of the lesser muscle volume at the abdomen, and it may be less affected for evaluating glycogen synthesis/degradation in the liver even without localization pulses.

  14. Relative contribution of muscle and liver insulin resistance to dysglycemia in postmenopausal overweight and obese women: A MONET group study.

    PubMed

    Elisha, Belinda; Disse, Emmanuel; Chabot, Katherine; Taleb, Nadine; Prud'homme, Denis; Bernard, Sophie; Rabasa-Lhoret, Rémi; Bastard, Jean-Philippe

    2017-02-01

    The relative contribution of muscle and liver insulin resistance (IR) in the development of dysglycemia and metabolic abnormalities is difficult to establish. The present study aimed to investigate the relative contribution of muscle IR vs. liver IR to dysglycemia in non-diabetic overweight or obese postmenopausal women and to determine differences in body composition and cardiometabolic indicators associated with hepatic or muscle IR. Secondary analysis of 156 non-diabetic overweight or obese postmenopausal women. Glucose tolerance was measured using an oral glucose tolerance test. Whole-body insulin sensitivity (IS) was determined as glucose disposal rate during a euglycemic-hyperinsulinemic clamp. Muscle and liver IR have been calculated using Abdul-Ghani et al. OGTT-derived formulas. Participant's body compositions as well as cardiometabolic risk indicators were also determined. Overall, 57 (36.5%) of patients had dysglycemia, among them 25 (16.0%); 21 (13.5%); 11 (7.1%) had impaired fasting glycemia, impaired glucose tolerance and combined glucose intolerance respectively. Fifty-three (34.0%) participants were classified as combined IS while on the opposite 51 participants (32.7%) were classified as combined IR and 26 (16.7%) participants had either muscle IR or liver IR. For similar body mass index and total fat mass, participants with liver IR were more likely to have lower whole-body IS, dysglycemia and higher visceral fat, liver fat index, triglycerides and alanine aminotransferase than participants with muscle IR. In the present study, the presence of liver IR is associated with a higher prevalence of dysglycemia, ectopic fat accumulation and metabolic abnormalities than muscle IR. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Involvement of human liver cytochrome P4502B6 in the metabolism of propofol

    PubMed Central

    Oda, Yutaka; Hamaoka, Naoya; Hiroi, Toyoko; Imaoka, Susumu; Hase, Ichiro; Tanaka, Kazuo; Funae, Yoshihiko; Ishizaki, Takashi; Asada, Akira

    2001-01-01

    Aims To determine the cytochrome P450 (CYP) isoforms involved in the oxidation of propofol by human liver microsomes. Methods The rate constant calculated from the disappearance of propofol in an incubation mixture with human liver microsomes and recombinant human CYP isoforms was used as a measure of the rate of metabolism of propofol. The correlation of these rate constants with rates of metabolism of CYP isoform-selective substrates by liver microsomes, the effect of CYP isoform-selective chemical inhibitors and monoclonal antibodies on propofol metabolism by liver microsomes, and its metabolism by recombinant human CYP isoforms were examined. Results The mean rate constant of propofol metabolism by liver microsomes obtained from six individuals was 4.2 (95% confidence intervals 2.7, 5.7) nmol min−1 mg−1 protein. The rate constants of propofol by microsomes were significantly correlated with S-mephenytoin N-demethylation, a marker of CYP2B6 (r = 0.93, P < 0.0001), but not with the metabolic activities of other CYP isoform-selective substrates. Of the chemical inhibitors of CYP isoforms tested, orphenadrine, a CYP2B6 inhibitor, reduced the rate constant of propofol by liver microsomes by 38% (P < 0.05), while other CYP isoform-selective inhibitors had no effects. Of the recombinant CYP isoforms screened, CYP2B6 produced the highest rate constant for propofol metabolism (197 nmol min−1 nmol P450−1). An antibody against CYP2B6 inhibited the disappearance of propofol in liver microsomes by 74%. Antibodies raised against other CYP isoforms had no effect on the metabolism of propofol. Conclusions CYP2B6 is predominantly involved in the oxidation of propofol by human liver microsomes. PMID:11298076

  16. Changes induced by dietary energy intake and divergent selection for muscle fat content in rainbow trout (Oncorhynchus mykiss), assessed by transcriptome and proteome analysis of the liver.

    PubMed

    Kolditz, Catherine-Ines; Paboeuf, Gilles; Borthaire, Maïena; Esquerré, Diane; SanCristobal, Magali; Lefèvre, Florence; Médale, Françoise

    2008-10-29

    Growing interest is turned to fat storage levels and allocation within body compartments, due to their impact on human health and quality properties of farm animals. Energy intake and genetic background are major determinants of fattening in most animals, including humans. Previous studies have evidenced that fat deposition depends upon balance between various metabolic pathways. Using divergent selection, we obtained rainbow trout with differences in fat allocation between visceral adipose tissue and muscle, and no change in overall body fat content. Transcriptome and proteome analysis were applied to characterize the molecular changes occurring between these two lines when fed a low or a high energy diet. We focused on the liver, center of intermediary metabolism and the main site for lipogenesis in fish, as in humans and most avian species. The proteome and transcriptome analyses provided concordant results. The main changes induced by the dietary treatment were observed in lipid metabolism. The level of transcripts and proteins involved in intracellular lipid transport, fatty acid biosynthesis and anti-oxidant metabolism were lower with the lipid rich diet. In addition, genes and proteins involved in amino-acid catabolism and proteolysis were also under expressed with this diet. The major changes related to the selection effect were observed in levels of transcripts and proteins involved in amino-acid catabolism and proteolysis that were higher in the fat muscle line than in the lean muscle line. The present study led to the identification of novel genes and proteins that responded to long term feeding with a high energy/high fat diet. Although muscle was the direct target, the selection procedure applied significantly affected hepatic metabolism, particularly protein and amino acid derivative metabolism. Interestingly, the selection procedure and the dietary treatment used to increase muscle fat content exerted opposite effects on the expression of the liver

  17. Isotretinoin-induced acute severe myopathy involving pelvic girdle muscles: A case report

    PubMed Central

    Sameem, Farah; Semira

    2016-01-01

    Oral isotretinoin has been in widespread use for more than three decades. It causes numerous side effects; skin and mucous membrane being commonly involved. Musculoskeletal adverse effects are also known to occur, but pelvic girdle myopathy is rarely reported. We report myopathy involving pelvic girdle muscles in a young male who received oral isotretinoin for folliculitis decalvans. PMID:27721552

  18. Iron regulates glucose homeostasis in liver and muscle via AMP-activated protein kinase in mice

    PubMed Central

    Huang, Jingyu; Simcox, Judith; Mitchell, T. Creighton; Jones, Deborah; Cox, James; Luo, Bai; Cooksey, Robert C.; Boros, Laszlo G.; McClain, Donald A.

    2013-01-01

    Excess iron is associated with hepatic damage and diabetes in humans, although the detailed molecular mechanisms are not known. To investigate how iron regulates glucose homeostasis, we fed C57BL/6J male mice with high-iron (HI) diets (2 or 20 g Fe/kg chow). Mice fed an HI diet exhibited elevated AMP-activated protein kinase (AMPK) activity and impaired insulin signaling in skeletal muscle and liver. Consistent with the increased AMPK activity, glucose uptake was enhanced in mice fed an HI diet. The effects of improved glucose tolerance induced by HI feeding were abolished in transgenic mice with expression of muscle specific dominant-negative AMPK. Glucose output was suppressed in the liver of wild-type mice fed an HI diet, due to decreased expression of gluconeogenic genes and decreased substrate (lactate) from peripheral glycolysis. Iron activated AMPK by increasing deacetylase and decreasing LKB1 acetylation, in turn stimulating the phosphorylation of LKB1 and AMPK. The effects of HI diet were abrogated by treatment of the mice with N-acetyl cysteine, suggesting a redox-dependent mechanism for increasing deacetylase activity. In addition, tissue from iron-fed mice exhibited an elevated AMP/ATP ratio, further contributing to AMPK activation. In summary, a diet high in iron improves glucose tolerance by activating AMPK through mechanisms that include deacetylation.—Huang J., Simcox, J., Mitchell, T. C., Jones, D., Cox, J., Luo, B., Cooksey, R. C., Boros, L. G., McClain, D. A. Iron regulates glucose homeostasis in liver and muscle via AMP-activated protein kinase in mice. PMID:23515442

  19. Salamander limb regeneration involves the activation of a multipotent skeletal muscle satellite cell population.

    PubMed

    Morrison, Jamie I; Lööf, Sara; He, Pingping; Simon, András

    2006-01-30

    In contrast to mammals, salamanders can regenerate complex structures after injury, including entire limbs. A central question is whether the generation of progenitor cells during limb regeneration and mammalian tissue repair occur via separate or overlapping mechanisms. Limb regeneration depends on the formation of a blastema, from which the new appendage develops. Dedifferentiation of stump tissues, such as skeletal muscle, precedes blastema formation, but it was not known whether dedifferentiation involves stem cell activation. We describe a multipotent Pax7+ satellite cell population located within the skeletal muscle of the salamander limb. We demonstrate that skeletal muscle dedifferentiation involves satellite cell activation and that these cells can contribute to new limb tissues. Activation of salamander satellite cells occurs in an analogous manner to how the mammalian myofiber mobilizes stem cells during skeletal muscle tissue repair. Thus, limb regeneration and mammalian tissue repair share common cellular and molecular programs. Our findings also identify satellite cells as potential targets in promoting mammalian blastema formation.

  20. Glycogen synthesis in liver and skeletal muscle after exercise: participation of the gluconeogenic pathway

    SciTech Connect

    Johnson, J.L.

    1986-01-01

    Hepatic glycogenesis occurs by both the uptake of plasma glucose (direct pathway) as well as from gluconeogenesis (indirect pathway). In vitro studies suggest that skeletal muscle can also synthesize glycogen from lactate. The purpose of the present studies was to assess the contribution of the indirect pathway to liver and muscle glycogen synthesis after exercise with various substrata infusions. The authors hypothesis was the contribution of the indirect pathway of hepatic glycogenesis would increase after exercise. To this end, fasted rats were depleted of glycogen by exhaustive exercise; a second group of fasted rats remained rested. Both groups were then infused intravenously with glucose containing tracer quantities of (6-/sup 3/H) and (U-/sup 14/C) glucose for 4 hrs. The ensuing hyperglycemic response was exaggerated in post-exercised rats; whereas, plasma lactate levels were lower than those of nonexercised rats. The percent of hepatic glycogen synthesized from gluconeogenic precursors did not differ between exercised (39%) and nonexercised (36%) rats.

  1. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    EPA Science Inventory

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  2. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    EPA Science Inventory

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  3. Concomitant Epstein-Barr Virus-associated smooth muscle tumor and granulomatous inflammation of the liver.

    PubMed

    Can, Nhu Thuy; Grenert, James P; Vohra, Poonam

    2017-07-13

    Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor typically seen in immunocompromised patients. Here, we report a case of EBV-SMT and associated granulomatous inflammation in the liver of a 32-year-old man with history of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). To our knowledge, an association of these two lesions has not been previously reported. We review the literature and discuss pathogenesis, differential diagnosis and immunohistochemical (IHC) stains helpful for the diagnosis of this rare entity. Finally, we consider possible explanations for the concomitant presence of these lesions. Published by Elsevier GmbH.

  4. Some biochemical effects of triamcinolone acetonide on rat liver and muscle.

    PubMed

    Peters, R F; Richardson, M C; Small, M; White, A M

    1970-02-01

    1. The powerful anti-inflammatory glucocorticoid triamcinolone acetonide, administered to rats at 20 and 2.5mg/kg, leads to a decrease in the incorporation in vivo of [(3)H]uridine and [(32)P]orthophosphate into hind-limb skeletal muscle. 2. At the higher dose, this decrease in the rate of incorporation of precursors into RNA precedes a decrease in the incorporating ability of muscle ribosomes, which commences about 4-5h after drug administration, but is unaccompanied by any changes in the concentration of tissue ATP or free amino acids. 3. The ribosomal dysfunction extends to polyribosomes, which can only be successfully isolated from the muscle of triamcinolone-treated animals after the addition of alpha-amylase to the tissue homogenate to remove glycogen. 4. The specific radioactivity of muscle protein labelled in vivo with (14)C-labelled amino acids does not decrease progressively after triamcinolone administration. After 2h there is an apparent stimulation of incorporation which leads to an overall discrepancy between measurements of protein-synthetic activity made in vivo and in vitro. 5. There is a significant increase in muscle-glycogen concentration between 8 and 12h after the administration of triamcinolone acetonide (20mg/kg), although a significant decrease occurs after 4h. The fall in glycogen concentration may be due to a decrease in the rate of synthesis of protein essential for glucose uptake into the tissues. 6. As judged by (a) incorporation of (14)C-labelled amino acids into protein, (b) [(3)H]uridine and [(32)P]-orthophosphate incorporation into RNA, (c) the rate of induction of tryptophan pyrrolase and (d) changes in the pool sizes of taurine and tryptophan, the responses in liver followed the same time-course as those in muscle after administration of the drug.

  5. The diurnal response of muscle and liver protein synthesis in vivo in meal-fed rats

    PubMed Central

    Garlick, P. J.; Millward, D. J.; James, W. P. T.

    1973-01-01

    1. The rate of protein synthesis in rat tissues was measured by constant intravenous infusion of [14C]tyrosine. A modification has been developed for the method of calculating the rate of protein synthesis in individual tissues from the specific radioactivity of the free and protein-bound amino acid in tissue at the end of the infusion. This technique gives greater accuracy and allows a greater choice of labelled amino acids. The specific radioactivity of free tyrosine in plasma was used to calculate the plasma tyrosine flux, an index of the rate of protein synthesis in the whole body. 2. Young male Wistar rats were allowed access to food for only 4h in every 24h. The tyrosine flux and the rate of protein synthesis in liver and muscle at different periods of time after a single feed were estimated. 3. The tyrosine flux did not alter after feeding nor even after starvation for 48h. 4. The average fractional rate of protein synthesis in muscle was 7.2%/day, i.e. the proportion of the protein mass which is replaced each day. The rate rose after eating and declined during starvation for 48h. In addition the rate of muscle protein synthesis correlated with the growth rate of the rat. 5. In liver the average fractional rate of protein synthesis was 50%/day. There was no change in the rate after eating nor after starvation for 48h. In contrast with muscle this suggests that the changes in protein mass were accompanied by changes in the rate of protein breakdown rather than synthesis. PMID:4786539

  6. The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice.

    PubMed

    Hamrick, M W; Dukes, A; Arounleut, P; Davis, C; Periyasamy-Thandavan, S; Mork, S; Herberg, S; Johnson, M H; Isales, C M; Hill, W D; Otvos, L; Belin de Chantemèle, E J

    2015-10-01

    Muscle- and liver-derived IGF-1 play important roles in muscle anabolism throughout growth and aging. Yet, prolonged food restriction is thought to increase longevity in part by lowering levels of IGF-1, which in turn reduces the risk for developing various cancers. The dietary factors that modulate IGF-1 levels are, however, poorly understood. We tested the hypothesis that the adipokine leptin, which is elevated with food intake and suppressed during fasting, is a key mediator of IGF-1 levels with aging and food restriction. First, leptin levels in peripheral tissues were measured in young mice fed ad libitum, aged mice fed ad libitum, and aged calorie-restricted (CR) mice. A group of aged CR mice were also treated with recombinant leptin for 10 days. Later, aged mice fed ad libitum were treated with saline (VEH) or with a novel leptin receptor antagonist peptide (Allo-aca) and tissue-specific levels of IGF-1 were determined. On one hand, recombinant leptin induced a three-fold increase in liver-derived IGF-1 and a two-fold increase in muscle-derived IGF-1 in aged, CR mice. Leptin also significantly increased serum growth hormone levels in the aged, CR mice. On the other, the leptin receptor antagonist Allo-aca did not alter body weight or muscle mass in treated mice compared to VEH mice. Allo-aca did, however, produce a significant (20%) decline in liver-derived IGF-1 as well as an even more pronounced (>50%) decrease in muscle-derived IGF-1 compared to VEH-treated mice. The reduced IGF-1 levels in Allo-aca treated mice were not accompanied by any significant change in growth hormone levels compared to VEH mice. These findings suggest that leptin receptor antagonists may represent novel therapeutic agents for attenuating IGF-1 signaling associated with aging, and could potentially mimic some of the positive effects of calorie restriction on longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Dose-dependent difference of nuclear receptors involved in murine liver hypertrophy by piperonyl butoxide.

    PubMed

    Sakamoto, Yohei; Yoshida, Midori; Tamura, Kei; Takahashi, Miwa; Kodama, Yukio; Inoue, Kaoru

    2015-12-01

    Nuclear receptors play important roles in chemically induced liver hypertrophy in rodents. To clarify the involvement of constitutive androstane receptor (CAR) and other nuclear receptors in mouse liver hypertrophy induced by different doses of piperonyl butoxide (PBO), wild-type and CAR-knockout mice were administered PBO (200, 1,000, or 5,000 ppm) in the basal diet for 1 week. Increased liver weight and diffuse hepatocellular hypertrophy were observed at 5,000 ppm for both genotypes, accompanied by increased Cyp3a11 mRNA and CYP3A protein expression, suggesting that CAR-independent pathway, possibly pregnane X receptor (PXR), plays a major role in the induction of hypertrophy. Moreover, wild-type mice at 5,000 ppm showed enhanced hepatocellular hypertrophy and strong positive staining for CYP2B in the centrilobular area, suggesting the localized contribution of CAR. At 1,000 ppm, only wild-type mice showed liver weight increase and centrilobular hepatocellular hypertrophy concurrent with elevated Cyp2b10 mRNA expression and strong CYP2B staining, indicating that CAR was essential at 1,000 ppm. We concluded that high-dose PBO induced hypertrophy via CAR and another pathway, while lower dose of PBO induced a pathway mediated predominantly by CAR. The dose-responsiveness on liver hypertrophy is important for understanding the involvement of nuclear receptors.

  8. Muscle involvement in limb-girdle muscular dystrophy with GMPPB deficiency (LGMD2T)

    PubMed Central

    Stojkovic, T.; Dahlqvist, J.R.; Bouchet-Seraphin, C.; Nectoux, J.; Leturcq, F.; Cossée, M.; Solé, G.; Thomsen, C.; Krag, T.O.; Vissing, J.

    2016-01-01

    Objective: In this study, muscle involvement assessed by MRI and levels of GMPPB and glycosylation of α-dystroglycan expression in muscle were examined in patients with limb-girdle muscular dystrophy (LGMD) type 2T. Methods: Six new patients with genetically verified mutations in GMPPB were studied. T1-weighted magnetic resonance images were obtained in 4 participants. Muscle strength and potential involvement of extramuscular organs were examined. Glycosylation of α-dystroglycan in muscle was studied, and GMPPB and α-dystroglycan expression was analyzed by Western blotting. Prevalence of LGMD2T was calculated from the total LGMD population in Denmark. GMPPB was sequenced in all unclassified cases. Results: Two patients carried 3 new mutations in GMPPB. The other 4 patients carried previously described pathogenic mutations in GMPPB. MRI showed that the paraspinal muscles were the most affected, followed by involvement of hamstrings. Our results showed a loss of glycosylation of α-dystroglycan as well as secondary loss of merosin expression on Western blotting. The prevalence of LGMD2T in the Danish cohort of patients with LGMD is 1.5%. Conclusions: The new findings of this study are (1) the consistent finding of a preferential affection of paraspinal and hamstring muscles in LGMD2T, (2) 3 new mutations in GMPPB, (3) variable loss of glycosylation tested with IIH6 and VIA4 antibodies, and (4) a prevalence of LGMD2T of 1.5% in a well-characterized Danish LGMD cohort. PMID:27766311

  9. Muscle and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice.

    PubMed

    Hoene, Miriam; Li, Jia; Li, Yanjie; Runge, Heike; Zhao, Xinjie; Häring, Hans-Ulrich; Lehmann, Rainer; Xu, Guowang; Weigert, Cora

    2016-02-26

    Intracellular lipid pools are highly dynamic and tissue-specific. Physical exercise is a strong physiologic modulator of lipid metabolism, but most studies focus on changes induced by long-term training. To assess the acute effects of endurance exercise, mice were subjected to one hour of treadmill running, and (13)C16-palmitate was applied to trace fatty acid incorporation in soleus and gastrocnemius muscle and liver. The amounts of carnitine, FFA, lysophospholipids and diacylglycerol and the post-exercise increase in acetylcarnitine were pronouncedly higher in soleus than in gastrocnemius. In the liver, exercise increased the content of lysophospholipids, plasmalogens and carnitine as well as transcript levels of the carnitine transporter. (13)C16-palmitate was detectable in several lipid and acylcarnitine species, with pronounced levels of tracer-derived palmitoylcarnitine in both muscles and a strikingly high incorporation into triacylglycerol and phosphatidylcholine in the liver. These data illustrate the high lipid storing activity of the liver immediately after exercise whereas in muscle, fatty acids are directed towards oxidation. The observed muscle-specific differences accentuate the need for single-muscle analyses as well as careful consideration of the particular muscle employed when studying lipid metabolism in mice. In addition, our results reveal that lysophospholipids and plasmalogens, potential lipid signalling molecules, are acutely regulated by physical exercise.

  10. Differential expression of genes involved in the calcium homeostasis in masticatory muscles of MDX mice.

    PubMed

    Kunert-Keil, C H; Gredes, T; Lucke, S; Botzenhart, U; Dominiak, M; Gedrange, T

    2014-04-01

    Duchenne Muscular Dystrophy (DMD) and its murine model, mdx, are characterized by Ca(2+) induced muscle damage and muscle weakness followed by distorted dentofacial morphology. In both, DMD patients and in mdx mice, could be proven so far that only the extraocular muscles (EOM) are not affected by muscular dystrophy. The EOMs are protected against calcium overload by enhanced expression of genes involved in the Ca(2+) homeostasis. We could recently demonstrate that masticatory muscles of mdx mice are differentially affected by muscle dystrophy. The dystrophic masseter and temporalis shows muscle histology comparable to all other skeletal muscles in this animal model, whereas dystrophic tongue muscles seem to develop a milder phenotype. Due to this fact it is to hypothesize that an altered Ca(2+) homeostasis seems to underlie the mdx masticatory muscle pathology. Aim of this study was to examine the mRNA and protein levels of the sarcoplasmic reticulum Ca(2+) ATPases SERCA1 and SERCA2, the plasma membrane Ca(2+) ATPases Atp2b1 and Atp2b4, the sodium/calcium exchanger NCX1, the ryanodine receptor 1, parvalbumin, sarcolipin, phospholamban and the L-type Ca(2+) channel alpha-1 subunit (Cacna1s) in Musculus masseter, temporalis, and tongue of 100 day old control and mdx mice. In mdx masseter muscle significant increased mRNA levels of NCX1 and Cacna1s were found compared to control mice. In contrast, the mRNA amount of RYR1 was significant reduced in mdx temporalis muscle, whereas ATP2b4 was significant increased. In mdx tongue a down-regulation of the ATP2b1, sarcolipin and parvalbumin mRNA expression was found, whereas the phospholamban mRNA level was significantly increased compared to controls. These data were verified by western blot analyses. Our findings revealed that mdx masticatory muscles showed an unequally altered expression of genes involved in the Ca(2+) homeostasis that can support the differences in masticatory muscles response to dystrophin deficiency.

  11. Unraveling the Molecular Signatures of Oxidative Phosphorylation to Cope with the Nutritionally Changing Metabolic Capabilities of Liver and Muscle Tissues in Farmed Fish

    PubMed Central

    Bermejo-Nogales, Azucena; Calduch-Giner, Josep Alvar; Pérez-Sánchez, Jaume

    2015-01-01

    Mitochondrial oxidative phosphorylation provides over 90% of the energy produced by aerobic organisms, therefore the regulation of mitochondrial activity is a major issue for coping with the changing environment and energy needs. In fish, there is a large body of evidence of adaptive changes in enzymatic activities of the OXPHOS pathway, but less is known at the transcriptional level and the first aim of the present study was to define the molecular identity of the actively transcribed subunits of the mitochondrial respiratory chain of a livestock animal, using gilthead sea bream as a model of farmed fish with a high added value for European aquaculture. Extensive BLAST searches in our transcriptomic database (www.nutrigroup-iats.org/seabreamdb) yielded 97 new sequences with a high coverage of catalytic, regulatory and assembly factors of Complex I to V. This was the basis for the development of a PCR array for the simultaneous profiling of 88 selected genes. This new genomic resource allowed the differential gene expression of liver and muscle tissues in a model of 10 fasting days. A consistent down-regulated response involving 72 genes was made by the liver, whereas an up-regulated response with 29 and 10 differentially expressed genes was found in white skeletal muscle and heart, respectively. This differential regulation was mostly mediated by nuclear-encoded genes (skeletal muscle) or both mitochondrial- and nuclear-encoded genes (liver, heart), which is indicative of a complex and differential regulation of mitochondrial and nuclear genomes, according to the changes in the lipogenic activity of liver and the oxidative capacity of glycolytic and highly oxidative muscle tissues. These insights contribute to the identification of the most responsive elements of OXPHOS in each tissue, which is of relevance for the appropriate gene targeting of nutritional and/or environmental metabolic disturbances in livestock animals. PMID:25875231

  12. Unraveling the molecular signatures of oxidative phosphorylation to cope with the nutritionally changing metabolic capabilities of liver and muscle tissues in farmed fish.

    PubMed

    Bermejo-Nogales, Azucena; Calduch-Giner, Josep Alvar; Pérez-Sánchez, Jaume

    2015-01-01

    Mitochondrial oxidative phosphorylation provides over 90% of the energy produced by aerobic organisms, therefore the regulation of mitochondrial activity is a major issue for coping with the changing environment and energy needs. In fish, there is a large body of evidence of adaptive changes in enzymatic activities of the OXPHOS pathway, but less is known at the transcriptional level and the first aim of the present study was to define the molecular identity of the actively transcribed subunits of the mitochondrial respiratory chain of a livestock animal, using gilthead sea bream as a model of farmed fish with a high added value for European aquaculture. Extensive BLAST searches in our transcriptomic database (www.nutrigroup-iats.org/seabreamdb) yielded 97 new sequences with a high coverage of catalytic, regulatory and assembly factors of Complex I to V. This was the basis for the development of a PCR array for the simultaneous profiling of 88 selected genes. This new genomic resource allowed the differential gene expression of liver and muscle tissues in a model of 10 fasting days. A consistent down-regulated response involving 72 genes was made by the liver, whereas an up-regulated response with 29 and 10 differentially expressed genes was found in white skeletal muscle and heart, respectively. This differential regulation was mostly mediated by nuclear-encoded genes (skeletal muscle) or both mitochondrial- and nuclear-encoded genes (liver, heart), which is indicative of a complex and differential regulation of mitochondrial and nuclear genomes, according to the changes in the lipogenic activity of liver and the oxidative capacity of glycolytic and highly oxidative muscle tissues. These insights contribute to the identification of the most responsive elements of OXPHOS in each tissue, which is of relevance for the appropriate gene targeting of nutritional and/or environmental metabolic disturbances in livestock animals.

  13. Melatonin increases intracellular calcium in the liver, muscle, white adipose tissues and pancreas of diabetic obese rats.

    PubMed

    Agil, A; Elmahallawy, E K; Rodríguez-Ferrer, J M; Adem, A; Bastaki, S M; Al-Abbadi, I; Fino Solano, Y A; Navarro-Alarcón, M

    2015-08-01

    Melatonin, a widespread substance with antioxidant and anti-inflammatory properties, has been found to act as an antidiabetic agent in animal models, regulating the release and action of insulin. However, the molecular bases of this antidiabetic action are unknown, limiting its application in humans. Several studies have recently shown that melatonin can modify calcium (Ca(2+)) in diabetic animals, and Ca(2+) has been reported to be involved in glucose homeostasis. The objective of the present study was to assess whether the antidiabetic effect of chronic melatonin at pharmacological doses is established via Ca(2+) regulation in different tissues in an animal model of obesity-related type 2 diabetes, using Zücker diabetic fatty (ZDF) rats and their lean littermates, Zücker lean (ZL) rats. After the treatments, flame atomic absorption spectrometry was used to determine Ca(2+) levels in the liver, muscle, main types of internal white adipose tissue, subcutaneous lumbar fat, pancreas, brain, and plasma. This study reports for the first time that chronic melatonin administration (10 mg per kg body weight per day for 6 weeks) increases Ca(2+) levels in muscle, liver, different adipose tissues, and pancreas in ZDF rats, although there were no significant changes in their brain or plasma Ca(2+) levels. We propose that this additional peripheral dual action mechanism underlies the improvement in insulin sensitivity and secretion previously documented in samples from the same animals. According to these results, indoleamine may be a potential candidate for the treatment of type 2 diabetes mellitus associated with obesity.

  14. Transcriptomics of liver and muscle in Holstein cows genetically divergent for fertility highlight differences in nutrient partitioning and inflammation processes.

    PubMed

    Moran, Bruce; Cummins, Sean B; Creevey, Christopher J; Butler, Stephen T

    2016-08-11

    The transition between pregnancy and lactation is a major physiological change for dairy cows. Complex systemic and local processes involving regulation of energy balance, galactopoiesis, utilisation of body reserves, insulin resistance, resumption of oestrous cyclicity and involution of the uterus can affect animal productivity and hence farm profitability. Here we used an established Holstein dairy cow model of fertility that displayed genetic and phenotypic divergence in calving interval. Cows had similar genetic merit for milk production traits, but either very good genetic merit for fertility traits ('Fert+'; n = 8) or very poor genetic merit for fertility traits ('Fert-'; n = 8). We used RNA sequencing to investigate gene expression profiles in both liver and muscle tissue biopsies at three distinct time-points: late pregnancy, early lactation and mid lactation (-18, 1 and 147 days relative to parturition, respectively). We found 807 and 815 unique genes to be differentially expressed in at least one time-point in liver and muscle respectively, of which 79 % and 83 % were only found in a single time-point; 40 and 41 genes were found differentially expressed at every time-point indicating possible systemic or chronic dysregulation. Functional annotation of all differentially expressed genes highlighted two physiological processes that were impacted at every time-point in the study, These were immune and inflammation, and metabolic, lipid and carbohydrate-binding. These pathways have previously been identified by other researchers. We show that several specific genes which are differentially regulated, including IGF-1, might impact dairy fertility. We postulate that an increased burden of reactive oxidation species, coupled with a chronic inflammatory state, might reduce dairy cow fertility in our model.

  15. Liver and muscle proteolytic activity in field bean (Vicia faba L.) fed birds. Effect of vitamin E.

    PubMed

    Santidrián, S; Rodríguez, M L; Larralde, J

    1987-09-01

    Liver and muscle proteolytic activities (cathepsin A and D) were measured in growing male chickens fed ad libitum over periods of 30 and 60 days on 20% protein diets containing either heated soybean (HSB, control) or raw field bean (RFB, Vicia faba L.) as the main sources of protein. Vitamin E (250 mg/100 g diet) was added or not to the RFB diet. It has been found that in comparison to control HSB-fed animals, RFB-fed birds showed a significant reduction in the rate of growth, together with a significant increase in the activities of both cathepsins A and D in liver and muscle. The addition of vitamin E to the RFB diet had no significant effect on either weight gain or liver and muscle proteolytic activities. The possible nature of these effects is discussed.

  16. Total and organic mercury in liver, kidney and muscle of waterbirds from wetlands of the Caspian Sea, Iran.

    PubMed

    Aazami, J; Esmaili-Saria, A; Bahramifar, N; Savabieasfahani, M

    2012-07-01

    We measured and compared total and organic mercury in liver, kidney, and muscle of the Great Cormorant (Phalacrocorax carbo), mallard (Anas platyrhynchos), and coot (Fulica atra) from the Caspian Sea wetlands in Iran. For the Great Cormorant organic mercury in liver, kidney and muscle comprised 82 %, 79 % and 58 % of total mercury. In the mallard same values were 46 %, 54 %, and 64 %. For coot total mercury was: 0.1 ± 0.0, 0.1 ± 0.01, 0.03 ± 0.01 in liver kidney and muscle respectively. We detected no organic mercury. In general older birds that feed on higher trophic levels can accumulate more mercury in their tissues.

  17. Effect of dietary lipid, carnitine and exercise on lipid profile in rat blood, liver and muscle.

    PubMed

    Karanth, Jyothsna; Jeevaratnam, K

    2009-09-01

    Aim of this study was to investigate the influence of physical exercise on effects of the daily intake of vegetarian diet of either vegetable hydrogenated fat (HF) or peanut oil (PO) with or without carnitine on the lipid profile. Eight groups of male Wistar rats were fed HF-diet (4 groups) or PO-diet (4 groups), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. Plasma triglycerides (TG), total cholesterol (TC), HDL-cholesterol, free fatty acids (FFA), liver and thigh muscle glycogen, total fat (TF), TG, TC and FFA were analyzed. HF-fed rats showed significantly increased plasma TC, VLDL+LDL-cholesterol and TG compared to PO-fed rats, wherein a lowered plasma TC, TG levels in all the groups with significantly increased liver cholesterol and decreased muscle cholesterol was observed. Physical exercise of moderate intensity reduced plasma TC and TG accompanied by significantly reduced tissue TG and cholesterol while FFA and glycogen increased in all the groups. The influence of exercise was less pronounced in carnitine supplemented rats since carnitine could significantly reduce TG in plasma and tissues of sedentary rats. Results from the present study showed that the intake of HF diet significantly increased the plasma and tissue lipid profile and MUFA-rich diet or carnitine supplementation and/or exercise may ameliorate the deleterious effects of HF.

  18. Differential accumulation of selenium among axial muscle, reproductive and liver tissues of four warmwater fish species

    SciTech Connect

    Sager, D.R.; Cofield, C.R.

    1984-06-01

    Bluegill (Lepomis macrochirus), largemouth bass (Micropterus salmoides), white catfish (Ictalurus catus), and channel catfish (Ictalurus punctatus), collected from an electric power plant cooling reservoir and a municipal water supply reservoir near Roxboro, North Carolina, were analyzed for selenium concentrations in axial muscle, reproductive and liver tissues. Fishes from the municipal water reservoir had lower selenium concentrations (<0.2-2.1 ..mu..g/g - wet weight) than found in the cooling reservoir fishes (1.6-70.0 ..mu..g/g - wet weight) but similar distributions of concentrations among the tissues was evident. Selenium was differentially accumulated, with higher concentrations in liver tissues (0.7 - 70.0 ..mu..g/g - wet weight), followed by female productive tissues (0.7 - 25.0 ..mu..g/g - wet weight), axial muscle tissues (< 0.2 - 23.0 ..mu..g/g - wet weight) and male reproductive tissues (0.02 - 7.2 ..mu..g/g - wet weight).

  19. The involvement of extracellular calcium in hypoxic injury to the isolated rat liver.

    PubMed

    Strubelt, O; Younes, M

    1988-09-01

    Isolated perfused livers from fasted rats were subjected to 30 min of hypoxia followed by 60 min of reoxygenation. At a calcium concentration of 1.25 mmol/l in the perfusate, hypoxia induced injury as evidenced by a marked release of GPT and SDH into the perfusate and by an accumulation of calcium in the livers. Omission of calcium from the perfusate attenuated hypoxia-induced enzyme release by about 50% and prevented the increase of hepatic calcium completely. A complete protection of the liver against hypoxic injury was attained in the absence of calcium when Na2 EDTA was added. An influx of calcium from the extracellular to the intracellular fluid seems to be involved in but is not the sole cause of hypoxia-induced hepatic injury.

  20. Interleukin-13 is involved in the formation of liver fibrosis in Clonorchis sinensis-infected mice.

    PubMed

    Xu, Yanquan; Liang, Pei; Bian, Meng; Chen, Wenjun; Wang, Xiaoyun; Lin, Jinsi; Shang, Mei; Qu, Hongling; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-07-01

    Clonorchiasis is a chronic infection disease often accompanied by formation of liver fibrosis. Previous study has identified that Clonorchis sinensis (C. sinensis, Cs) infection and CsRNASET2 (a member of CsESPs) immunization can drive Th2 immune response. IL-13, a multifunctional Th2 cytokine, has been widely confirmed to be profibrotic mediator. We want to determine whether IL-13 is involved in the generation of liver fibrosis during C. sinensis infection. A part of mice were infected with C. sinensis or immunized with CsRNASET2, respectively. Another part of mice were intravenously injected with rIL-13. Liver tissues of C. sinensis-infected mice were stained with hematoxylin-eosin and Masson's trichrome, respectively. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of infected mice and rIL-13-treated mice were measured by quantitative RT-PCR. Besides, splenocytes of C. sinensis-infected and CsRNASET2-immunized mice were isolated, respectively. The levels of IL-13 in splenocytes were detected by ELISA. Our results displayed that the livers of C. sinensis-infected mice had serious chronic inflammation and collagen deposition. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of C. sinensis-infected mice were obviously increased. Splenocytes from both C. sinensis-infected and CsRNASET2-immunized mice expressed high levels of IL-13. Moreover, rIL-13 treatment markedly promoted the transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1. These data implied that hepatic fibrosis was formed in the livers of C. sinensis-infected mice, and IL-13 induced by C. sinensis infection and CsRNASET2 immunization might favor this progression.

  1. IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture.

    PubMed

    Lara-Diaz, V J; Castilla-Cortazar, I; Martín-Estal, I; García-Magariño, M; Aguirre, G A; Puche, J E; de la Garza, R G; Morales, L A; Muñoz, U

    2017-05-01

    Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1(+/-), and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.

  2. Effects of shock waves on oxidative stress and some trace element levels of rat liver and diaphragm muscles.

    PubMed

    Gecit, İlhan; Kavak, Servet; Meral, Ismail; Güneş, Mustafa; Pirinççi, Necip; Sayir, Fuat; Demir, Halit; Ceylan, Kadir

    2012-06-01

    This study was designed to investigate whether the short-term extracorporeal shockwave lithotripsy (ESWL) exposure to kidney produces an oxidative stress and a change in some trace element levels in liver and diaphragm muscles of rats. Twelve male Wistar albino rats were divided randomly into two groups, each consisting of six rats. The animals in the first group did not receive any treatment and served as control group. The right-side kidneys of animals in group 2 were treated with two-thousand 18 kV shock waves while anesthetized with 50 mg kg(-1) ketamine. The localization of the right kidney was achieved after contrast medium injection through a tail vein under fluoroscopy control. The animals were killed 72 h after the ESWL treatment, and liver and diaphragm muscles were harvested for the determination of tissue oxidative stress and trace element levels. Although the malondialdehyde level increased, superoxide dismutase and glutathione peroxidase enzyme activities decreased in the livers and diaphragm muscles of ESWL-treated rats. Although glutathione level increased in liver, it decreased in diaphragm muscles of ESWL-treated animals. Fe, Mg and Mn levels decreased, and Cu and Pb levels increased in the livers of ESWL-treated animals. Fe and Cu levels increased, and Mg, Pb, Mn and Zn levels decreased in the diaphragm muscles of ESWL-treated animals. It also causes a decrease or increase in many mineral levels in liver and diaphragm muscles, which is an undesirable condition for the normal physiological function of tissues. Copyright © 2012 John Wiley & Sons, Ltd.

  3. A comparative study of accumulated total mercury among white muscle, red muscle and liver tissues of common carp and silver carp from the Sanandaj Gheshlagh Reservoir in Iran.

    PubMed

    Khoshnamvand, Mehdi; Kaboodvandpour, Shahram; Ghiasi, Farzad

    2013-01-01

    The Sanandaj Gheshlagh Reservoir (SGR) is a mercury polluted lake that is located in the West of Iran. Common carp (Cyprinus carpio) and silver carp (Hypophthalmichthys molitrix) are the most abundant fishes in the SGR. A total of 48 common and silver carps (24 each) were captured randomly, using 50×6 m gill net (mesh size: 5×5 cm) during July to December 2009. Each month, the levels of accumulated total mercury (T-Hg) in white muscle, red muscle and liver tissues of these fishes were measured using an Advanced Mercury Analyzer (Model; Leco 254 AMA, USA) on the dry weight basis. There were no statistically significant differences between T-Hg concentrations in white muscle, red muscle and liver in common carp in comparison with similar tissues in silver carp (P>0.05). The content of T-Hg in liver tissue of both species was lower than of white and red muscle tissues. Higher levels of accumulated T-Hg were observed during summer. Results showed that T-Hg concentrations in common and silver carps target tissues were strongly dependent on age, length and weight (P<0.05). The results indicated that the levels of accumulated T-Hg in tissues of all samples with weights of over 850 g were greater than those limits established by WHO and FAO (500 ng g(-1)). Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation

    PubMed Central

    Zaouali, Mohamed Amine; Panisello, Arnau; Lopez, Alexandre; Castro, Carlos; Folch, Emma; Carbonell, Teresa; Rolo, Anabela; Palmeira, Carlos Marques; Garcia-Gil, Agustin; Adam, René; Roselló-Catafau, Joan

    2017-01-01

    We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia–reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured. The AKT protein kinase and its direct substrates, GSK3β and VDAC, as well as caspases 3, 9, and cytochrome C and reticulum endoplasmic stress-related proteins (GRP78, pPERK, ATF4, and CHOP), were determined by Western blot. IGL-1+TMZ significantly reduced liver injury. We also observed a significant phosphorylation of AKT, which in turn induced the phosphorylation and inhibition of GSK3β. In addition, TMZ protected the mitochondria since, in comparison with IGL-1 alone, we found reductions in VDAC phosphorylation, apoptosis, and GLDH release. All these results were correlated with decreased ER stress. Addition of TMZ to IGL-1 solution increased the tolerance of the liver graft to I/R injury through inhibition of GSK3β and VDAC, contributing to ER stress reduction and cell death prevention. PMID:28282906

  5. Systematic review of genetic association studies involving histologically confirmed non-alcoholic fatty liver disease

    PubMed Central

    Wood, Kayleigh L; Miller, Michael H; Dillon, John F

    2015-01-01

    Non-alcoholic fatty liver disease has an increasing prevalence in Western countries, affecting up to 20% of the population. Objective The aim of this project was to systematically review and summarise the genetic association studies that investigate possible genetic influences that confer susceptibility to non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Design The MEDLINE and SCOPUS databases were searched to identify candidate gene studies on histologically diagnosed non-alcoholic fatty liver disease. Results A total of 85 articles have been summarised and categorised on the basis of the general pathway each candidate gene is involved in, including lipid metabolism, lipoprotein processing, cholesterol synthesis, glucose homoeostasis, inflammatory response, protection against oxidative stress and whole body metabolism. Conclusions The main findings demonstrate a small but consistent association of PNPLA3 with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Genetic association studies have investigated general disease susceptibility, histological characteristics, severity and progression. However, further study is required to better elucidate the genetic factors influencing fatty liver disease. PMID:26462272

  6. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico

    PubMed Central

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-01-01

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features. PMID:26556986

  7. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico.

    PubMed

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-11-07

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features.

  8. Leg Muscle Involvement in Facioscapulohumeral Muscular Dystrophy: Comparison between Facioscapulohumeral Muscular Dystrophy Types 1 and 2.

    PubMed

    Mair, Dorothea; Huegens-Penzel, Monika; Kress, Wolfram; Roth, Christian; Ferbert, Andreas

    2017-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) presents with 2 genetically distinct types. We describe for the first time the MRI patterns of leg muscle involvement in type 2 and compare it with type 1. The intramuscular fat content was assessed on lower extremity axial T1-weighted MRI scans in 6 FSHD1 and 5 FSHD2 patients. Overall, the muscle involvement profile did not differ substantially between FSHD1 and FSHD2. In the thigh, the dorsomedial compartment including the semimembranosus, semitendinosus and adductor magnus was the most affected. The quadriceps was mostly spared, but isolated involvement of the rectus femoris was common. Fat infiltration in the distal soleus and the medial gastrocnemius with sparing of the lateral gastrocnemius was a common finding; involvement of the tibialis anterior was less frequent. A proximal-to-distal increase in fat content was frequently present in some muscles. Muscle involvement appears to be independent of type, confirming a similar pathophysiological pathway in FSHD1 and FSHD2. © 2016 S. Karger AG, Basel.

  9. Insulin immuno-neutralization in fed chickens: effects on liver and muscle transcriptome.

    PubMed

    Simon, Jean; Milenkovic, Dragan; Godet, Estelle; Cabau, Cedric; Collin, Anne; Métayer-Coustard, Sonia; Rideau, Nicole; Tesseraud, Sophie; Derouet, Michel; Crochet, Sabine; Cailleau-Audouin, Estelle; Hennequet-Antier, Christelle; Gespach, Christian; Porter, Tom E; Duclos, Michel J; Dupont, Joëlle; Cogburn, Larry A

    2012-03-01

    Chickens mimic an insulin-resistance state by exhibiting several peculiarities with regard to plasma glucose level and its control by insulin. To gain insight into the role of insulin in the control of chicken transcriptome, liver and leg muscle transcriptomes were compared in fed controls and "diabetic" chickens, at 5 h after insulin immuno-neutralization, using 20.7K-chicken oligo-microarrays. At a level of false discovery rate <0.01, 1,573 and 1,225 signals were significantly modified by insulin privation in liver and muscle, respectively. Microarray data agreed reasonably well with qRT-PCR and some protein level measurements. Differentially expressed mRNAs with human ID were classified using Biorag analysis and Ingenuity Pathway Analysis. Multiple metabolic pathways, structural proteins, transporters and proteins of intracellular trafficking, major signaling pathways, and elements of the transcriptional control machinery were largely represented in both tissues. At least 42 mRNAs have already been associated with diabetes, insulin resistance, obesity, energy expenditure, or identified as sensors of metabolism in mice or humans. The contribution of the pathways presently identified to chicken physiology (particularly those not yet related to insulin) needs to be evaluated in future studies. Other challenges include the characterization of "unknown" mRNAs and the identification of the steps or networks, which disturbed tissue transcriptome so extensively, quickly after the turning off of the insulin signal. In conclusion, pleiotropic effects of insulin in chickens are further evidenced; major pathways controlled by insulin in mammals have been conserved despite the presence of unique features of insulin signaling in chicken muscle.

  10. Content of total iron, copper and manganese in liver of animals during hypokinesia, muscle activity and process of recovery

    NASA Technical Reports Server (NTRS)

    Potapovich, G. M.; Taneyeva, G. V.; Uteshev, A. B.

    1980-01-01

    It is shown that the content of total iron, copper and manganese in the liver of animals is altered depending on the intensity and duration of their swimming. Hypodynamia for 7 days does not alter the concentration of iron, but sufficiently increases the content of copper and manganese. The barometric factor effectively influences the maintenance of constancy in the content of microelements accumulated in the liver after intensive muscle activity.

  11. Effects of dissolved oxygen on glycolytic enzyme specific activities in liver and skeletal muscle of Fundulus heteroclitus.

    PubMed

    Abbaraju, Naga V; Rees, Bernard B

    2012-06-01

    Many aquatic habitats are characterized by variable concentrations of dissolved oxygen (DO), and fish that occur in these habitats respond to changes in DO through behavioral, physiological, and biochemical adjustments. The goal of the present study was to measure the effects of an ecologically relevant range of DO treatments, from severe hypoxia to moderate hyperoxia, on the maximal activities of nine glycolytic enzymes during chronic exposure of the mummichog, Fundulus heteroclitus. Over the 28 days of exposure period, specific activity was significantly affected by DO for three enzymes in liver and one enzyme in white skeletal muscle, although at specific times of exposure three other muscle enzymes were affected by DO. In general, exposure of fish to severe hypoxia led to higher specific activities in liver, but lower specific activities in skeletal muscle. Exposure to hyperoxia did not elicit changes in enzyme specific activities in either tissue. Surprisingly, exposure duration had strong effects on glycolytic enzyme specific activities in both liver and white skeletal muscle, with specific activities increasing with exposure duration regardless of DO treatment. The results demonstrate that the effects of DO on enzyme specific activities were restricted to a subset of the glycolytic enzymes in liver and white skeletal muscle of F. heteroclitus and that the directions of the changes were opposite in these two tissues. These observations suggest that the mechanisms resulting in these alterations are enzyme- and tissue specific, rather than applying uniformly to all enzymes within the glycolytic pathway.

  12. Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved

    PubMed Central

    Chen, Ji-an; Splenser, Andres; Guillory, Bobby; Luo, Jiaohua; Mendiratta, Meenal; Belinova, Blaga; Halder, Tripti; Zhang, Guohua; Li, Yi-Ping; Garcia, Jose M

    2015-01-01

    Background Cachexia and muscle atrophy are common consequences of cancer and chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake and direct effects on muscle proteolysis and protein synthesis are likely to mediate these effects, but the pathways leading to these events are not well understood. Methods We characterized molecular pathways involved in muscle atrophy induced by Lewis lung carcinoma (LLC) tumour implantation in c57/bl6 adult male mice and by administration of the chemotherapeutic agent cisplatin in mice and in C2C12 myotubes. The effects of exogenous ghrelin administration and its mechanisms of action were examined in these settings. Results Tumour implantation and cisplatin induced muscle atrophy by activating pro-inflammatory cytokines, p38-C/EBP-β, and myostatin, and by down-regulating Akt, myoD, and myogenin, leading to activation of ubiquitin-proteasome-mediated proteolysis and muscle weakness. Tumour implantation also increased mortality. In vitro, cisplatin up-regulated myostatin and atrogin-1 by activating C/EBP-β and FoxO1/3. Ghrelin prevented these changes in vivo and in vitro, significantly increasing muscle mass (P < 0.05 for LLC and P < 0.01 for cisplatin models) and grip strength (P = 0.038 for LLC and P = 0.001 for cisplatin models) and improving survival (P = 0.021 for LLC model). Conclusion Ghrelin prevents muscle atrophy by down-regulating inflammation, p38/C/EBP-β/myostatin, and activating Akt, myogenin, and myoD. These changes appear, at least in part, to target muscle cells directly. Ghrelin administration in this setting is associated with improved muscle strength and survival. PMID:26136189

  13. Quantitative Assessment of Trunk Muscles Involvement in Patients with Myotonic Dystrophy Type 1 Using a Whole Body Muscle Magnetic Resonance Imaging.

    PubMed

    Park, Donghwi; Park, Jin-Sung

    2017-01-01

    The aim of this study was to analyze the pattern of trunk muscles involvement through a muscle MRI, in relation to the clinical data of patients diagnosed with myotonic dystrophy type 1 (DM1). Patients with DM1 who visited the neurology department were enrolled (n = 19). In all patients, the fatty degeneration of the muscle MRI in the lower cervical, upper thoracic, middle thoracic, and lumbosacral spine extensor muscle group and trunk flexor muscle group was evaluated. Clinical data, including CTG repeats, spinal deformity were analyzed to find the correlations with the fatty degeneration of trunk muscles in the muscle MRI. All DM1 patients who presented with very mild to severe functional status showed T1-weghted high intensity signals in the upper-thoracic spine extensor muscle group. The sum MRI score of the spine extensor muscle group showed a significant correlation with the 6-min walking test, and Cobb's angle. DM1 frequently affects the trunk muscles, even in the early stage of disease progression, regardless of disease severity or age of onset. Among the para-vertebral muscles, the selective involvement of spine extensor muscles may explain the cause of spinal deformities, which mirrors the functional status of DM1. © 2017 S. Karger AG, Basel.

  14. MicroRNA-21 is involved in ionizing radiation-promoted liver carcinogenesis

    PubMed Central

    Zhu, Yun; Yu, Xiaoyan; Fu, Hanjiang; Wang, Hongyan; Wang, Ping; Zheng, Xiaofei; Wang, Ya

    2010-01-01

    It has been known for decades that ionizing radiation (IR) promotes carcinogenesis and high-linear energy transfer (LET) IR has a higher risk than low-LET IR for carcinogenesis; however, the mechanism remains unclear. MicroRNAs (miRNAs) have a critical effect on carcinogenesis through post-transcriptional modification. In this study, our purpose is to explore whether miRNAs are involved in IR-(especially high-LET IR) promoted liver carcinogenesis. We showed here that among several hundred miRNAs, miR-21 was the only one that increased 6 folds in high-LET IR-promoted mouse liver tumors when compared with that in the non-irradiated liver tissues. We also showed that miR-21 was up-regulated in human or mouse hepatocytes after exposure to IR, as well as in liver tissues derived from whole body irradiated mice. The increased level of miR-21 was more significant in high-LET irradiated cells or liver tissues. After the non-irradiated, low-LET or high-LET irradiated human hepatocytes were over-expressed with miR-21, these cells became tumorigenesis in nude mice. The tumors derived from high-LET-irradiated-cells were largest, and accompanied by more significant changes in the miR-21-targets: PTEN and RECK. In addition, we showed that IR-induced up-regulation of miR-21 depended on the up-regulation/activation of AP-1 (at an earlier time, within 2 h) and the ErbB/Stat3 pathway (at a later time, more than 2 h), which was also IR dose dependent. Taken together, we conclude that IR-induced up-regulation of miR-21 plays an important role in IR (especially high-LET IR)-promoted liver carcinogenesis. PMID:20827319

  15. Organochlorine contaminants in the muscle, liver and brain of seabirds (Larus) from the coastal area of the Southern Baltic.

    PubMed

    Falkowska, Lucyna; Reindl, Andrzej R; Grajewska, Agnieszka; Lewandowska, Anita U

    2016-11-01

    The presence of persistent organic pollutants in the environment manifests itself most strongly in the marine trophic chain, where the highest link is comprised of seabirds. At the same time, seabirds are excellent indicators of contamination in their habitat. The present study concentrates on toxic substances: polychlorinated dibenzo-p-dioxin (PCDDs), polychlorinated dibenzofurans (PCDFs) and chlorinated organic pesticides (OCPs) accumulated in the livers, pectoral muscles and brains of dead gulls collected along the Polish coast of the Baltic Sea in the years 2010-12. The highest toxic equivalence was determined in the livers of Larus argentatus (TEQ(birds TEF)-28.3pgg(-1) ww) and Larus marinus (TEQ(birds TEF)-29.9pgg(-1) ww.). However, the toxic equivalence of muscles was lower and amounted to 3.9pgg(-1) ww. and 7.8pgg(-1) ww. respectively for the two species. The lowest toxic equivalence was found in the brains of birds, where only one, the most toxic, 2,3,7,8 TCDD congener was found (TEQ(birds TEF) 0.87pgg(-1) ww). The highest concentration of chloroorganic pesticides was determined in the brains of the birds (total OCP 167.8pgg(-1) ww.), lower concentrations were found in the livers (total OCP 92.1pgg(-1) ww.) and muscles (total OCP 43.1pgg(-1) ww.). With regard to pesticides, the highest proportion in the total OCP content was constituted by DDT and its isomers (liver 81%, muscles 77% and brain 55%). High concentrations of the studied pollutants in the livers of gulls found dead on the coast of the Southern Baltic could have been effected by levels of contamination in the birds' last meals, which resulted in a seven-fold increase of the liver's toxic equivalence and a two-fold increase in OCP concentration in relation to muscles.

  16. Hydatid Disease Involved in the Heart, Liver, and Kidney That Caused Sudden Death: Case Report.

    PubMed

    Daş, Taner; Özer, Mehmet; Yağmur, Gülhan; Yildirim, Muzaffer; Özgün, Ayşe; Demirel, Hüsrev

    2015-12-01

    Hydatid disease is a parasitic infestation caused by ingestion of eggs of echinococcal species. For Echinococcus granulosus, the definitive host is the dog, and sheeps are the usual intermediate hosts. Humans are accidental intermediate hosts, infected by ingestion of food contaminated with eggs shed by dogs or foxes. The most common organs that hydatid disease encountered are the liver and lungs. Involvement of the kidney is rare and usually accompanies the other organ involvements. Cardiac involvement of echinococcosis is also very rare. We report the case of a 31-year-old woman with a 6-year history of asthma who collapsed after strenuous activity and died despite the interventions carried out. At autopsy, cystic masses were detected in the apex of the heart, in the right kidney, and in the liver. There were no macroscopic pathologic findings in the other organs. Microscopic examination revealed the diagnosis of hydatid cyst in the heart, right kidney, and liver besides medial hypertrophy of the lung vessels. Cause of death was attributed to hydatid cyst and its complications. Patients who have symptoms akin to asthma at clinical presentation have to be further investigated for organic cardiac and pulmonary diseases such as hydatid cyst, especially in endemic countries.

  17. Involvement of MicroRNAs in the Regulation of Muscle Wasting during Catabolic Conditions*

    PubMed Central

    Soares, Ricardo José; Cagnin, Stefano; Chemello, Francesco; Silvestrin, Matteo; Musaro, Antonio; De Pitta, Cristiano; Lanfranchi, Gerolamo; Sandri, Marco

    2014-01-01

    Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure, and in aging. In fact, excessive proteolysis causes cachexia, accelerates disease progression, and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes, and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, whereas transcriptional control of the atrophy-related genes peaks at 3 days, changes of miRNA expression maximized at 7 days after denervation. Among the different miRNAs, microRNA-206 and -21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for fine-tuning the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions. PMID:24891504

  18. Involvement of microRNAs in the regulation of muscle wasting during catabolic conditions.

    PubMed

    Soares, Ricardo José; Cagnin, Stefano; Chemello, Francesco; Silvestrin, Matteo; Musaro, Antonio; De Pitta, Cristiano; Lanfranchi, Gerolamo; Sandri, Marco

    2014-08-08

    Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure, and in aging. In fact, excessive proteolysis causes cachexia, accelerates disease progression, and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes, and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, whereas transcriptional control of the atrophy-related genes peaks at 3 days, changes of miRNA expression maximized at 7 days after denervation. Among the different miRNAs, microRNA-206 and -21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for fine-tuning the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions.

  19. TNF-α- and tumor-induced skeletal muscle atrophy involves sphingolipid metabolism.

    PubMed

    De Larichaudy, Joffrey; Zufferli, Alessandra; Serra, Filippo; Isidori, Andrea M; Naro, Fabio; Dessalle, Kevin; Desgeorges, Marine; Piraud, Monique; Cheillan, David; Vidal, Hubert; Lefai, Etienne; Némoz, Georges

    2012-01-18

    Muscle atrophy associated with various pathophysiological conditions represents a major health problem, because of its contribution to the deterioration of patient status and its effect on mortality. Although the involvement of pro-inflammatory cytokines in this process is well recognized, the role of sphingolipid metabolism alterations induced by the cytokines has received little attention. We addressed this question both in vitro using differentiated myotubes treated with TNF-α, and in vivo in a murine model of tumor-induced cachexia. Myotube atrophy induced by TNF-α was accompanied by a substantial increase in cell ceramide levels, and could be mimicked by the addition of exogenous ceramides. It could be prevented by the addition of ceramide-synthesis inhibitors that targeted either the de novo pathway (myriocin), or the sphingomyelinases (GW4869 and 3-O-methylsphingomyelin). In the presence of TNF-α, ceramide-synthesis inhibitors significantly increased protein synthesis and decreased proteolysis. In parallel, they lowered the expression of both the Atrogin-1 and LC3b genes, involved in muscle protein degradation by proteasome and in autophagic proteolysis, respectively, and increased the proportion of inactive, phosphorylated Foxo3 transcription factor. Furthermore, these inhibitors increased the expression and/or phosphorylation levels of key factors regulating protein metabolism, including phospholipase D, an activator of mammalian target of rapamycin (mTOR), and the mTOR substrates S6K1 and Akt. In vivo, C26 carcinoma implantation induced a substantial increase in muscle ceramide, together with drastic muscle atrophy. Treatment of the animals with myriocin reduced the expression of the atrogenes Foxo3 and Atrogin-1, and partially protected muscle tissue from atrophy. Ceramide accumulation induced by TNF-α or tumor development participates in the mechanism of muscle-cell atrophy, and sphingolipid metabolism is a logical target for pharmacological or

  20. TNF-α- and tumor-induced skeletal muscle atrophy involves sphingolipid metabolism

    PubMed Central

    2012-01-01

    Background Muscle atrophy associated with various pathophysiological conditions represents a major health problem, because of its contribution to the deterioration of patient status and its effect on mortality. Although the involvement of pro-inflammatory cytokines in this process is well recognized, the role of sphingolipid metabolism alterations induced by the cytokines has received little attention. Results We addressed this question both in vitro using differentiated myotubes treated with TNF-α, and in vivo in a murine model of tumor-induced cachexia. Myotube atrophy induced by TNF-α was accompanied by a substantial increase in cell ceramide levels, and could be mimicked by the addition of exogenous ceramides. It could be prevented by the addition of ceramide-synthesis inhibitors that targeted either the de novo pathway (myriocin), or the sphingomyelinases (GW4869 and 3-O-methylsphingomyelin). In the presence of TNF-α, ceramide-synthesis inhibitors significantly increased protein synthesis and decreased proteolysis. In parallel, they lowered the expression of both the Atrogin-1 and LC3b genes, involved in muscle protein degradation by proteasome and in autophagic proteolysis, respectively, and increased the proportion of inactive, phosphorylated Foxo3 transcription factor. Furthermore, these inhibitors increased the expression and/or phosphorylation levels of key factors regulating protein metabolism, including phospholipase D, an activator of mammalian target of rapamycin (mTOR), and the mTOR substrates S6K1 and Akt. In vivo, C26 carcinoma implantation induced a substantial increase in muscle ceramide, together with drastic muscle atrophy. Treatment of the animals with myriocin reduced the expression of the atrogenes Foxo3 and Atrogin-1, and partially protected muscle tissue from atrophy. Conclusions Ceramide accumulation induced by TNF-α or tumor development participates in the mechanism of muscle-cell atrophy, and sphingolipid metabolism is a logical

  1. Gene Expression and Correlation of Pten and Fabp4 in Liver, Muscle, and Adipose Tissues of Type 2 Diabetes Rats.

    PubMed

    Su, Di; Zhang, Chuan-Ling; Gao, Ying-Chun; Liu, Xiao-Ying; Li, Cai-Ping; Huangfu, Jian; Xiao, Rui

    2015-11-22

    The aim of this work was to study the Fabp4 and Pten gene expression and correlation in the liver, muscle, and adipose tissues of type 2 diabetes mellitus (T2DM) rats. Male Wistar rats (8 weeks old) were randomly divided into 2 groups (n=12/group): a control group fed a normal diet for 8 weeks and an experimental group fed a high-fat, high-sugar diet for 8 weeks and that received 25 mg/kg streptozotocin by intraperitoneal injection to induce T2DM. The random blood glucose, fasting blood glucose, and fasting insulin levels were measured. The expression of Pten and Fabp4 in the liver, muscle, and epididymal adipose tissues was estimated by real-time quantitative PCR. Pearson correlation coefficient analysis was used to investigate the expression correlation between Pten and Fabp4 in T2DM rats. The gene expressions of Pten and Fabp4 in the liver, muscle, and adipose tissues of T2DM rats were all significantly higher than those in the control group (P<0.05). Pten was highly expressed in the muscles and Fabp4 was highly expressed in muscle and adipose tissues. Furthermore, expressions of Fabp4 and Pten in the muscle and adipose tissues of T2DM rats were positively correlated (P<0.05), but not in the liver. The increased expression of PTEN and FABP4 in the adipose and muscles of T2DM rats may play an important role in the insulin resistance of T2DM. However, the mechanism by which these 2 genes function in T2DM needs further study.

  2. Skeletal Muscle Satellite Cells, Mitochondria, and MicroRNAs: Their Involvement in the Pathogenesis of ALS.

    PubMed

    Tsitkanou, Stavroula; Della Gatta, Paul A; Russell, Aaron P

    2016-01-01

    Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal motor neuron disorder. It results in progressive degeneration and death of upper and lower motor neurons, protein aggregation, severe muscle atrophy and respiratory insufficiency. Median survival with ALS is between 2 and 5 years from the onset of symptoms. ALS manifests as either familial ALS (FALS) (~10% of cases) or sporadic ALS (SALS), (~90% of cases). Mutations in the copper/zinc (CuZn) superoxide dismutase (SOD1) gene account for ~20% of FALS cases and the mutant SOD1 mouse model has been used extensively to help understand the ALS pathology. As the precise mechanisms causing ALS are not well understood there is presently no cure. Recent evidence suggests that motor neuron degradation may involve a cell non-autonomous phenomenon involving numerous cell types within various tissues. Skeletal muscle is now considered as an important tissue involved in the pathogenesis of ALS by activating a retrograde signaling cascade that degrades motor neurons. Skeletal muscle heath and function are regulated by numerous factors including satellite cells, mitochondria and microRNAs. Studies demonstrate that in ALS these factors show various levels of dysregulation within the skeletal muscle. This review provides an overview of their dysregulation in various ALS models as well as how they may contribute individually and/or synergistically to the ALS pathogenesis.

  3. Identification of quantitative trait transcripts for growth traits in the large scales of liver and muscle samples.

    PubMed

    Xiong, Xinwei; Yang, Hui; Yang, Bin; Chen, Congying; Huang, Lusheng

    2015-07-01

    Growth-related traits are economically important traits to the pig industry. Identification of causative gene and mutation responsible for growth-related QTL will facilitate the improvement of pig growth through marker-assisted selection. In this study, we applied whole genome gene expression and quantitative trait transcript (QTT) analyses in 497 liver and 586 longissimus dorsi muscle samples to identify candidate genes and dissect the genetic basis of pig growth in a white Duroc × Erhualian F2 resource population. A total of 20,108 transcripts in liver and 23,728 transcripts in muscle with expression values were used for association analysis between gene expression level and phenotypic value. At the significance threshold of P < 0.0005, we identified a total of 169 and 168 QTTs for nine growth-related traits in liver and muscle, respectively. We also found that some QTTs were correlated to more than one trait. The QTTs identified here showed high tissue specificity. We did not identify any QTTs that were associated with one trait in both liver and muscle. Through an integrative genomic approach, we identified SDR16C5 as the important candidate gene in pig growth trait. These findings contribute to further identification of the causative genes for porcine growth traits and facilitate improvement of pig breeding.

  4. Coffee improves insulin-stimulated Akt phosphorylation in liver and skeletal muscle in diabetic KK-A(y) mice.

    PubMed

    Kobayashi, Misato; Matsuda, Yuji; Iwai, Hiroshi; Hiramitsu, Masanori; Inoue, Takashi; Katagiri, Takao; Yamashita, Yoko; Ashida, Hitoshi; Murai, Atsushi; Horio, Fumihiko

    2012-01-01

    Coffee has an anti-diabetic effect, specifically the amelioration of both hyperglycemia and insulin resistance, in KK-A(y) mice, a type 2 diabetes animal model. To investigate coffee's effect on insulin signaling in liver, skeletal muscle, and adipose tissue (epididymal fat), we assayed the tyrosine phosphorylation of insulin receptor (IR) and serine phosphorylation of Akt. In Expt. 1, we assayed insulin signaling under nonfasting conditions in KK-A(y) mice that ingested water or coffee for 4 wk. Coffee ingestion ameliorated the development of hyperglycemia but did not affect insulin signaling in liver or skeletal muscle under such conditions. In Expt. 2, we assayed insulin signaling under basal and insulin-stimulated conditions in KK-A(y) mice that ingested water or coffee for 3 wk. The levels of tyrosine phosphorylation of insulin receptor in response to insulin injection in insulin-sensitive tissues were not different between mice that drank water and those that drank coffee. Coffee ingestion significantly increased the insulin-induced serine phosphorylation of Akt in liver and skeletal muscle, but not in epididymal fat, of KK-A(y) mice. Our results also indicated that coffee ingestion may contribute to the improvement of insulin resistance and hyperglycemia in KK-A(y) mice via the activation of Akt in insulin signaling in liver and skeletal muscle.

  5. [Changes in myocardium, skeletal muscle and liver of rats fed carnitine-deficient diet and treated with carnitine optical isomers].

    PubMed

    Spasov, A A; Iezhitsa, I N; Pisarev, V B; Snigur, G L; Kravchenko, M S

    2006-01-01

    The aim of the present study was a comparative assessment of L-, D-and DL-carnitine effect on morphometric and histological parameters of myocardium, skeletal muscles (m. gastrocnemius) and liver in 60 rats fed carnitine-deficient diet. Carnitine-deficient diet fed 2 months resulted in a substantial reduction of carnitine concentration in blood plasma of rats. In carnitine-deficient animals, lipid vacuoles were found to accumulate within the hepatocytes in all the zones of hepatic lobules, which mainly had the character of micro- and macrovesicular steatosis. This was accompanied by a reduction of skeletal muscle fiber and cardiomyocyte average thickness. L-carnitine administration resulted in the compensation of carnitine deficiency in animals with alimentary carnitine deficient state, while the racemate and D-stereoisomere did not affect its content in blood. Pharmacological correction of carnitine deficiency with L-carnitine prevented the development of liver fatty dystrophy to a greater degree, than the administration of other carnitine stereoisomeres and promoted the restoration of muscular fiber thickness of skeletal muscles. DL-carnitine administration was accompanied by a moderate correction of fatty dystrophy and did not prevent the development of skeletal muscles atrophy. D-carnitine stereoisomere did not prevent liver fatty dystrophy, but it reduced its severity. Correction of carnitine deficiency with D- stereoisomere was not accompanied by essential morphological and morphometric differences in degree of skeletal muscle atrophy.

  6. Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth-muscle cell proliferation.

    PubMed Central

    Southgate, K M; Davies, M; Booth, R F; Newby, A C

    1992-01-01

    We investigated the influence of two structurally unrelated inhibitors of matrix-degrading metalloproteinases, Ro 31-4724 and Ro 31-7467, on the primary proliferation of smooth-muscle cells from rabbit aortic explants. Both agents inhibited proliferation in a concentration-dependent manner, but did not affect cell viability. Smooth-muscle cells grown out from explants secreted 95 kDa and 72 kDa gelatinase enzymes that were also inhibited in a concentration-dependent manner by Ro 31-4724 and Ro 31-7467. Interstitial collagenase and stromelysin were not detected. We conclude that metalloproteinases are likely to be involved in the initiation of smooth-muscle proliferation. Images Fig. 2. Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:1445285

  7. Dyspnea and respiratory muscle strength in end-stage liver disease

    PubMed Central

    Kaltsakas, Georgios; Antoniou, Efstathios; Palamidas, Anastasios F; Gennimata, Sofia-Antiopi; Paraskeva, Panorea; Smyrnis, Anastasios; Koutsoukou, Antonia; Milic-Emili, Joseph; Koulouris, Nickolaos G

    2013-01-01

    AIM: To investigate the prevalence of chronic dyspnea and its relationship to respiratory muscle function in end-stage liver disease. METHODS: Sixty-eight consecutive, ambulatory, Caucasian patients with end-stage liver disease, candidates for liver transplantation, were referred for preoperative respiratory function assessment. Forty of these (29 men) were included in this preliminary study after applying strict inclusion and exclusion criteria. Seventeen of 40 patients (42%) had ascites, but none of them was cachectic. Fifteen of 40 patients (38%) had a history of hepatic encephalopathy, though none of them was symptomatic at study time. All patients with a known history and/or presence of co-morbidities were excluded. Chronic dyspnea was rated according to the modified medical research council (mMRC) 6-point scale. Liver disease severity was assessed according to the Model for end-stage liver disease (MELD). Routine lung function tests, maximum static expiratory (Pemax) and inspiratory (Pimax) mouth pressures were measured. Respiratory muscle strength (RMS) was calculated from Pimax and Pemax values. In addition, arterial blood gases and pattern of breathing (VE: minute ventilation; VT: tidal volume; VT/TI: mean inspiratory flow; TI: duration of inspiration) were measured. RESULTS: Thirty-five (88%) of 40 patients aged (mean ± SD) 52 ± 10 years reported various degrees of chronic dyspnea (mMRC), ranging from 0 to 4, with a mean value of 2.0 ± 1.2. MELD score was 14 ± 6. Pemax, percent of predicted (%pred) was 105 ± 35, Pimax, %pred was 90 ± 29, and RMS, %pred was 97 ± 30. These pressures were below the normal limits in 12 (30%), 15 (38%), and 14 (35%) patients, respectively. Furthermore, comparing the subgroups of ascites to non-ascites patients, all respiratory muscle indices measured were found significantly decreased in ascites patients. Patients with ascites also had a significantly worse MELD score compared to non-ascites ones (P = 0

  8. Mercury and arsenic in muscle and liver of the golden cownose ray, Rhinoptera steindachneri, Evermann and Jenkins, 1891, from the upper Gulf of California, México.

    PubMed

    Gutiérrez-Mejía, E; Lares, M L; Sosa-Nishizaki, O

    2009-08-01

    Mercury and arsenic levels in muscle and liver of Rhinoptera steindachneri were determined in organisms collected in 2006. Element concentrations in both tissues were directly related to size. Maxima mean concentrations of Hg and As (0.41 and 59.9 microg g(-1) dry wt, respectively) were found in adults muscle. Mercury concentrations were significantly different between juveniles and adults in muscle and liver. For As concentrations, differences between juveniles and adults were found only in muscle. Mercury concentrations were higher in muscle of juveniles and adults. Arsenic concentrations were higher in liver of juveniles, and in muscle of adults. Maximum Hg concentration in muscle (0.65 microg g(-1) dry wt) was below the safe limit established by Mexican regulations for seafood.

  9. Involvement of the H+/organic cation antiporter in nicotine transport in rat liver.

    PubMed

    Tega, Yuma; Akanuma, Shin-Ichi; Kubo, Yoshiyuki; Hosoya, Ken-Ichi

    2015-01-01

    Nicotine is an addictive alkaloid in cigarette smoke and is responsible for tobacco dependence. It is important to consider the blood-to-liver transport of nicotine to understand the nicotine elimination from the body because most of the nicotine is converted to inactive metabolites by cytochrome P450 localized in the endoplasmic reticulum of the hepatocytes. In this study, the blood-to-liver transport of nicotine was investigated by means of an in vivo portal vein injection technique in rats, and the in vitro uptake by freshly isolated rat hepatocytes was used to clarify its mechanism. The results obtained showed that the in vivo blood-to-liver transport of [(3)H]nicotine was significantly inhibited by 50 mM nicotine and pyrilamine, suggesting involvement of a carrier-mediated transport process in the blood-to-liver transport of nicotine. The in vitro uptake study using freshly isolated rat hepatocytes showed a time- and concentration-dependent uptake of [(3)H]nicotine with a Km value of 141 µM, and the uptake was increased under alkaline extracellular conditions. In addition, intracellular acidification caused an increase in [(3)H]nicotine uptake, suggesting that the influx transport of nicotine is driven by an oppositely directed H(+) gradient in hepatocytes. Moreover, [(3)H]nicotine uptake was strongly inhibited in the presence of cationic drugs, such as pyrilamine, whereas only weak inhibitory effects were shown by substrates of typical organic cation transporters, such as tetraethylammonium, 1-methyl-4-phenylpyridinium, choline, and l-carnitine. In conclusion, a carrier-mediated system controlling the blood-to-liver transport of nicotine appears to be present on the sinusoidal membrane of hepatocytes. The pattern of inhibition and ion dependence is suggestive of an H(+)/organic cation antiporter-mediated nicotine transport system.

  10. Residues of sulfadiazine and doxycycline in broiler liver and muscle tissue due to cross-contamination of feed.

    PubMed

    Vandenberge, V; Delezie, E; Huyghebaert, G; Delahaut, P; Daeseleire, E; Croubels, S

    2012-01-01

    Veterinary drugs, such as antimicrobial compounds, are widely used in poultry and may lead to the presence of residues in matrices of animal origin, such as muscle and liver tissue. In this study, broilers received an experimental feed containing sulfadiazine or doxycycline at cross-contamination levels of 2.5, 5 and 10% of the therapeutic dose in feed. Breast and thigh muscle and liver samples were collected during treatment and depletion period and analysed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations reached a plateau phase 3-5 days after the start of experimental feeding. A rapid depletion of residues was noted after withdrawal of the experimental feed. No significant differences in measured concentrations were observed between the various muscle types. Residue concentrations for some experimental groups; the 10% group of sulfadiazine and the 5 and 10% group of doxycycline, however, exceeded their corresponding maximum residue limits (MRLs).

  11. Membrane effects of Vitamin E deficiency: bioenergetic and surface-charge-density studies of skeletal muscle and liver mitochondria

    SciTech Connect

    Quintanilha, A.T.; Packer, L.; Szyszlo Davies, J.M.; Racanelli, T.L.; Davies, K.J.A.

    1981-12-01

    Vitamin E (dl-..cap alpha..-tocopherol) deficiency in rats increased the sensitivity of liver and muscle mitochondria to damage during incubation at various temperatures, irradiation with visible light, or steady state respiration with substrates. In all cases, vitamin E deficient mitochondria exhibited increased lipid peroxidation, reduced transmembrane potential, decreased respiratory coupling, and lower rates of electron transport, compared to control mitochondria. Muscle mitochondria always showed greater negative inner membrane surface charge density, and were also more sensitive to damage than were liver mitochondria. Vitamin E deficient mitochondria also showed slightly more negative inner membrane surface charge density compared to controls. The relationship between greater negative surface potential and increased sensitivity to damage observed, provides for a new and sensitive method to further probe the role of surface charge in membrane structure and function. Implications of these new findings for the well known human muscle myopathies and those experimentally induced by Vitamin E deficiency in animals, are discussed.

  12. Microcystin accumulation in liver and muscle of tilapia in two large Brazilian hydroelectric reservoirs.

    PubMed

    Deblois, Charles P; Aranda-Rodriguez, Rocio; Giani, Alessandra; Bird, David F

    2008-03-01

    The objective of this study was to measure levels of the toxin microcystin in different tissues of fish known to feed on cyanobacteria during toxic bloom events. Wild Nile and redbreast tilapia (Oreochromis niloticus and Tilapia rendalli) were sampled from the catch of artisanal fishermen at eutrophic stations of Funil and Furnas reservoirs in southeastern Brazil. Phytoplankton communities in the two reservoirs were quite different taxonomically, but not dissimilar in microcystin content (200 microg g dry weight (DW) seston(-1) at Funil, 800 microg gDW seston(-1) at Furnas). All of the 27 fish sampled contained microcystin, ranging from 0.8 to 32.1 microg g liver(-1) and from 0.9 to 12.0 ng g muscle(-1). Most microcystin variants found in seston were also found in fish liver. T. rendalli had the lowest concentration in both tissues when compared to O. niloticus. In both reservoirs, one of every four fish sampled, always O. niloticus, had a level of microcystins beyond the World Health Organization tolerable daily intake (8 ng g tissue(-1)) and represented a risk for consumers. It is possible that closer study of inter-species variability in toxin burden in cyanobacteria-impacted water bodies will permit the development of guidelines for fish consumption that will better protect public health.

  13. Differential involvement of orbital fat and extraocular muscles in graves' ophthalmopathy.

    PubMed

    Wiersinga, Wilmar M; Regensburg, Noortje I; Mourits, Maarten P

    2013-03-01

    Graves' ophthalmopathy (GO) is characterized by swelling of orbital fat and extraocular muscles, but little attention has been given to differential involvement of fat and muscles. Advancements in imaging allow rather accurate measurements of orbital bony cavity volume (OV), fat volume (FV) and muscle volume (MV), and are the topics of this review. Ratios of FV/OV and MV/OV neutralize gender differences. In adult Caucasian controls, mean values ± SD of FV/OV are 0.56 ± 0.11 and of MV/OV are 0.15 ± 0.02. FV increases substantially and MV decreases slightly with advancing age, requiring age-specific reference ranges. In 95 consecutive untreated Caucasian GO patients, both FV and MV were within normal limits in 25%, increased FV but normal MV was present in 5%, normal FV but increased MV was detected in 61%, and both increased FV and MV was evident in 9%. Increased FV was associated with more proptosis and longer GO duration. Increased MV was associated with older age, more severe GO (more proptosis and diplopia, worse eye muscle ductions), higher TBII and current smoking. At the cellular and molecular level differential involvement of fat and muscles might be related to differences between fibroblast phenotypes and cytokine profiles in each compartment, to different orbital T cell subsets during the course of the disease and to peroxisome proliferator activator receptor-γ polymorphisms and modulation of 11β-hydroxysteroid dehydrogenase-1. Enlarged muscles are apparently a rather early phenomenon in GO, whereas increases in fat mass occur relatively late. Why a minor subset of GO patients presents with an increase of only fat remains poorly understood.

  14. Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction.

    PubMed

    Liu, Ming-Yu; Jin, Jing; Li, Shan-Liang; Yan, Jie; Zhen, Chang-Lin; Gao, Jin-Lai; Zhang, Yong-Hui; Zhang, Yan-Qiu; Shen, Xin; Zhang, Liang-Shuan; Wei, Yuan-Yuan; Zhao, Yu; Wang, Chen-Guang; Bai, Yun-Long; Dong, De-Li

    2016-11-01

    Mitochondria are dynamic organelles and continuously undergo fission and fusion processes. Mitochondrial fission is involved in multiple physiological or pathological processes, but the role of mitochondrial fission of smooth muscle cells in artery constriction is unknown. The role of mitochondrial fission of smooth muscle cells in arterial function was investigated by measuring the tension of rat mesenteric arteries and thoracic aorta and by evaluating mitochondrial fission, mitochondrial reactive oxygen species, and cytosolic [Ca(2+)]i in rat vascular smooth muscle cells. Mitochondrial fission inhibitors mdivi-1 and dynasore antagonized phenylephrine- and high K(+)-induced constriction of rat mesenteric arteries. Mdivi-1 relaxed phenylephrine-induced constriction, and mdivi-1 pretreatment prevented phenylephrine-induced constriction in mice, rat aorta, and human mesenteric arteries. Phenylephrine- and high K(+)-induced increase of mitochondrial fission in smooth muscle cells of rat aorta and the increase was inhibited by mdivi-1. Mdivi-1 inhibited high K(+)-induced increases of mitochondrial fission, mitochondrial reactive oxygen species, and cytosolic [Ca(2+)]i in rat vascular smooth muscle cells. Prechelation of cytosolic Ca(2+) prevented high K(+)-induced cytosolic [Ca(2+)]i increase, mitochondrial fission, and mitochondrial reactive oxygen species overproduction. Mitochondria-targeted antioxidant mito-TEMPO antagonized phenylephrine- and high K(+)-induced constriction of rat mesenteric arteries. Nitroglycerin and ROCK (Rho-associated protein kinase) inhibitor Y27632, the 2 vasodilators with different vasorelaxant mechanisms, relaxed high K(+)-induced vasoconstriction and inhibited high K(+)-induced mitochondrial fission. In conclusion, the mitochondrial fission of smooth muscle cells is involved in artery constriction. © 2016 American Heart Association, Inc.

  15. Mechanosensitive Molecular Networks Involved in Transducing Resistance Exercise-Signals into Muscle Protein Accretion

    PubMed Central

    Rindom, Emil; Vissing, Kristian

    2016-01-01

    Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion. Recent findings suggest specific upstream exercise-induced mechano-sensitive myocellular signaling pathways to converge on mammalian target of rapamycin complex 1 (mTORC1), to influence MPS. This may e.g. implicate mechanical activation of signaling through a diacylglycerol kinase (DGKζ)-phosphatidic acid (PA) axis or implicate integrin deformation to signal through a Focal adhesion kinase (FAK)-Tuberous Sclerosis Complex 2 (TSC2)-Ras homolog enriched in brain (Rheb) axis. Moreover, since initiation of translation is reliant on mRNA, it is also relevant to consider potentially mechanosensitive signaling pathways involved in muscle myofibrillar gene transcription and whether some of these pathways converge with those affecting mTORC1 activation for MPS. In this regard, recent findings suggest how mechanical stress may implicate integrin deformation and/or actin dynamics to signal through a Ras homolog gene family member A protein (RhoA)-striated muscle activator of Rho signaling (STARS) axis or implicate deformation of Notch to affect Bone Morphogenetic Protein (BMP) signaling through a small mother of decapentaplegic (Smad) axis. PMID:27909410

  16. Mechanosensitive Molecular Networks Involved in Transducing Resistance Exercise-Signals into Muscle Protein Accretion.

    PubMed

    Rindom, Emil; Vissing, Kristian

    2016-01-01

    Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion. Recent findings suggest specific upstream exercise-induced mechano-sensitive myocellular signaling pathways to converge on mammalian target of rapamycin complex 1 (mTORC1), to influence MPS. This may e.g. implicate mechanical activation of signaling through a diacylglycerol kinase (DGKζ)-phosphatidic acid (PA) axis or implicate integrin deformation to signal through a Focal adhesion kinase (FAK)-Tuberous Sclerosis Complex 2 (TSC2)-Ras homolog enriched in brain (Rheb) axis. Moreover, since initiation of translation is reliant on mRNA, it is also relevant to consider potentially mechanosensitive signaling pathways involved in muscle myofibrillar gene transcription and whether some of these pathways converge with those affecting mTORC1 activation for MPS. In this regard, recent findings suggest how mechanical stress may implicate integrin deformation and/or actin dynamics to signal through a Ras homolog gene family member A protein (RhoA)-striated muscle activator of Rho signaling (STARS) axis or implicate deformation of Notch to affect Bone Morphogenetic Protein (BMP) signaling through a small mother of decapentaplegic (Smad) axis.

  17. Absence of Aquaporin-4 in Skeletal Muscle Alters Proteins Involved in Bioenergetic Pathways and Calcium Handling

    PubMed Central

    Basco, Davide; Nicchia, Grazia Paola; D'Alessandro, Angelo; Zolla, Lello; Svelto, Maria; Frigeri, Antonio

    2011-01-01

    Aquaporin-4 (AQP4) is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4 on the morphology and protein composition of sarcolemma as well as on the whole skeletal muscle proteome. Immunofluorescence analysis showed that the absence of AQP4 did not perturb the expression and cellular localization of the dystrophin-glycoprotein complex proteins, aside from those belonging to the extracellular matrix, and no alteration was found in sarcolemma integrity by dye extravasation assay. With the use of a 2DE-approach (BN/SDS-PAGE), protein maps revealed that in quadriceps, out of 300 Coomassie-blue detected and matched spots, 19 proteins exhibited changed expression in AQP4−/− compared to WT mice. In particular, comparison of the protein profiles revealed 12 up- and 7 down-regulated protein spots in AQP4−/− muscle. Protein identification by MS revealed that the perturbed expression pattern belongs to proteins involved in energy metabolism (i.e. GAPDH, creatine kinase), as well as in Ca2+ handling (i.e. parvalbumin, SERCA1). Western blot analysis, performed on some significantly changed proteins, validated the 2D results. Together these findings suggest AQP4 as a novel determinant in the regulation of skeletal muscle metabolism and better define the role of this water channel in skeletal muscle physiology. PMID:21552523

  18. Absence of aquaporin-4 in skeletal muscle alters proteins involved in bioenergetic pathways and calcium handling.

    PubMed

    Basco, Davide; Nicchia, Grazia Paola; D'Alessandro, Angelo; Zolla, Lello; Svelto, Maria; Frigeri, Antonio

    2011-04-28

    Aquaporin-4 (AQP4) is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4 on the morphology and protein composition of sarcolemma as well as on the whole skeletal muscle proteome. Immunofluorescence analysis showed that the absence of AQP4 did not perturb the expression and cellular localization of the dystrophin-glycoprotein complex proteins, aside from those belonging to the extracellular matrix, and no alteration was found in sarcolemma integrity by dye extravasation assay. With the use of a 2DE-approach (BN/SDS-PAGE), protein maps revealed that in quadriceps, out of 300 Coomassie-blue detected and matched spots, 19 proteins exhibited changed expression in AQP4(-/-) compared to WT mice. In particular, comparison of the protein profiles revealed 12 up- and 7 down-regulated protein spots in AQP4-/- muscle. Protein identification by MS revealed that the perturbed expression pattern belongs to proteins involved in energy metabolism (i.e. GAPDH, creatine kinase), as well as in Ca(2+) handling (i.e. parvalbumin, SERCA1). Western blot analysis, performed on some significantly changed proteins, validated the 2D results. Together these findings suggest AQP4 as a novel determinant in the regulation of skeletal muscle metabolism and better define the role of this water channel in skeletal muscle physiology.

  19. Consumption of sucrose and high-fructose corn syrup does not increase liver fat or ectopic fat deposition in muscles.

    PubMed

    Bravo, Stephen; Lowndes, Joshua; Sinnett, Stephanie; Yu, Zhiping; Rippe, James

    2013-06-01

    It has been postulated that fructose-induced triglyceride synthesis is augmented when accompanied by glucose. Chronic elevations could lead to excess fat accumulation in the liver and ectopic fat deposition in muscles, which in turn could contribute to the induction of abnormalities in glucose homeostasis, insulin resistance, and the subsequent development of type 2 diabetes. Our objective was to evaluate the effect of the addition of commonly consumed fructose- and (or) glucose-containing sugars in the usual diet on liver fat content and intramuscular adipose tissue. For 10 weeks, 64 individuals (mean age, 42.16 ± 11.66 years) consumed low-fat milk sweetened with either high-fructose corn syrup (HFCS) or sucrose; the added sugar matched consumption levels of fructose in the 25th, 50th, and 90th percentiles of the population. The fat content of the liver was measured with unenhanced computed tomography imaging, and the fat content of muscle was assessed with magnetic resonance imaging. When the 6 HFCS and sucrose groups were averaged, there was no change over the course of 10 weeks in the fat content of the liver (13.32% ± 10.49% vs. 13.21% ± 10.75%; p > 0.05), vastus lateralis muscle (3.07 ± 0.74 g per 100 mL vs. 3.15 ± 0.84 g per 100 mL; p > 0.05), or gluteus maximus muscle (4.08 ± 1.50 g per 100 mL vs. 4.24 ± 1.42 g per 100 mL; p > 0.05). Group assignment did not affect the result (interaction > 0.05). These data suggest that when fructose is consumed as part of a typical diet in normally consumed sweeteners, such as sucrose or HFCS, ectopic fat storage in the liver or muscles is not promoted.

  20. Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland

    PubMed Central

    Alves, Susana P.; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J. B.; Almeida, André M.

    2015-01-01

    Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases. PMID:26678792

  1. Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells.

    PubMed

    Kranendonk, Mariëtte E G; Visseren, Frank L J; van Herwaarden, Joost A; Nolte-'t Hoen, Esther N M; de Jager, Wilco; Wauben, Marca H M; Kalkhoven, Eric

    2014-10-01

    Insulin resistance (IR) is a key mechanism in obesity-induced cardiovascular disease. To unravel mechanisms whereby human adipose tissue (AT) contributes to systemic IR, the effect of human AT-extracellular vesicles (EVs) on insulin signaling in liver and muscle cells was determined. EVs released from human subcutaneous (SAT) and omental AT (OAT)-explants ex vivo were used for stimulation of hepatocytes and myotubes in vitro. Subsequently, insulin-induced Akt phosphorylation and expression of gluconeogenic genes (G6P, PEPCK) was determined. AT-EV adipokine levels were measured by multiplex immunoassay, and AT-EVs were quantified by high-resolution flow cytometry. In hepatocytes, AT-EVs from the majority of patients inhibited insulin-induced Akt phosphorylation, while EVs from some patients stimulated insulin-induced Akt phosphorylation. In myotubes AT-EVs exerted an ambiguous effect on insulin signaling. Hepatic Akt phosphorylation related negatively to G6P-expression by both SAT-EVs (r = -0.60, P = 0.01) and OAT-EVs (r = -0.74, P = 0.001). MCP-1, IL-6, and MIF concentrations were higher in OAT-EVs compared to SAT-EVs and differently related to lower Akt phosphorylation in hepatocytes. Finally, the number of OAT-EVs correlated positively with liver enzymes indicative for liver dysfunction. Human AT-EVs can stimulate or inhibit insulin signaling in hepatocytes- possibly depending on their adipokine content- and may thereby contribute to systemic IR. Copyright © 2014 The Obesity Society.

  2. Factors involved in strain-induced injury in skeletal muscles and outcomes of prolonged exposures.

    PubMed

    Stauber, William T

    2004-02-01

    Repetitive motion disorders can involve lengthening of skeletal muscles to perform braking actions to decelerate limbs under load often resulting in muscle strains and injury. Injury is a loss of isometric force (weakness) requiring days to recover. The capacity of skeletal muscle to tolerate repeated strains is dependent on multiple factors including individual variation. The most important factors producing muscle strain injury are the magnitude of the resisting force (peak-stretch force) and the number of strains. Other factors such as muscle length and fiber type contribute to the susceptibility to injury as well, but to a lesser degree. Strain injury can also lead to inflammation and pain. Chronic exposure to repeated strains can result in fibrosis that is not completely reversed after months of rest. Long rest times appear to be the only factor reported to prevent inflammation in rats following repeated strain injury. Further understanding of the mechanism for prevention of histopathologic changes by long rest times should provide a rationale for prevention of negative outcomes.

  3. Identification, Isolation and Expansion of Myoendothelial Cells Involved in Leech Muscle Regeneration

    PubMed Central

    Grimaldi, Annalisa; Banfi, Serena; Gerosa, Laura; Tettamanti, Gianluca; Noonan, Douglas M.; Valvassori, Roberto; de Eguileor, Magda

    2009-01-01

    Adult skeletal muscle in vertebrates contains myoendothelial cells that express both myogenic and endothelial markers, and which are able to differentiate into myogenic cells to contribute to muscle regeneration. In spite of intensive research efforts, numerous questions remain regarding the role of cytokine signalling on myoendothelial cell differentiation and muscle regeneration. Here we used Hirudo medicinalis (Annelid, leech) as an emerging new model to study myoendothelial cells and muscle regeneration. Although the leech has relative anatomical simplicity, it shows a striking similarity with vertebrate responses and is a reliable model for studying a variety of basic events, such as tissue repair. Double immunohistochemical analysis were used to characterize myoendothelial cells in leeches and, by injecting in vivo the matrigel biopolymer supplemented with the cytokine Vascular Endothelial Growth Factor (VEGF), we were able to isolate this specific cell population expressing myogenic and endothelial markers. We then evaluated the effect of VEGF on these cells in vitro. Our data indicate that, similar to that proposed for vertebrates, myoendothelial cells of the leech directly participate in myogenesis both in vivo and in vitro, and that VEGF secretion is involved in the recruitment and expansion of these muscle progenitor cells. PMID:19876402

  4. Illusion caused by vibration of muscle spindles reveals an involvement of muscle spindle inputs in regulating isometric contraction of masseter muscles.

    PubMed

    Tsukiboshi, Taisuke; Sato, Hajime; Tanaka, Yuto; Saito, Mitsuru; Toyoda, Hiroki; Morimoto, Toshifumi; Türker, Kemal Sitki; Maeda, Yoshinobu; Kang, Youngnam

    2012-11-01

    Spindle Ia afferents may be differentially involved in voluntary isometric contraction, depending on the pattern of synaptic connections in spindle reflex pathways. We investigated how isometric contraction of masseter muscles is regulated through the activity of their muscle spindles that contain the largest number of intrafusal fibers among skeletal muscle spindles by examining the effects of vibration of muscle spindles on the voluntary isometric contraction. Subjects were instructed to hold the jaw at resting position by counteracting ramp loads applied on lower molar teeth. In response to the increasing-ramp load, the root mean square (RMS) of masseter EMG activity almost linearly increased under no vibration, while displaying a steep linear increase followed by a slower increase under vibration. The regression line of the relationship between the load and RMS was significantly steeper under vibration than under no vibration, suggesting that the subjects overestimated the ramp load and excessively counteracted it as reflected in the emergence of bite pressure. In response to the decreasing-ramp load applied following the increasing one, the RMS hardly decreased under vibration unlike under no vibration, leading to a generation of bite pressure even after the offset of the negative-ramp load until the vibration was ceased. Thus the subjects overestimated the increasing rate of the load while underestimating the decreasing rate of the load, due to the vibration-induced illusion of jaw opening. These observations suggest that spindle Ia/II inputs play crucial roles both in estimating the load and in controlling the isometric contraction of masseter muscles in the jaw-closed position.

  5. Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes.

    PubMed

    Kim, Kyoung-Ah; Chung, Jaegul; Jung, Dong-Hae; Park, Ji-Young

    2004-10-01

    The purpose of the present study was to elucidate the cytochrome P450 (P450) isoform(s) involved in the metabolism of loperamide (LOP) to N-demethylated LOP (DLOP) in human liver microsomes. Three established approaches were used to identify the P450 isoforms responsible for LOP N-demethylation using human liver microsomes and cDNA-expressed P450 isoforms: (1) correlation of LOP N-demethylation activity with marker P450 activities in a panel of human liver microsomes, (2) inhibition of enzyme activity by P450-selective inhibitors, and (3) measurement of DLOP formation by cDNA-expressed P450 isoforms. The relative contribution of P450 isoforms involved in LOP N-demethylation in human liver microsomes were estimated by applying relative activity factor (RAF) values. The formation rate of DLOP showed biphasic kinetics, suggesting the involvement of multiple P450 isoforms. Apparent Km and Vmax values were 21.1 microM and 122.3 pmol/min per milligram of protein for the high-affinity component and 83.9 microM and 412.0 pmol/min per milligram of protein for the low-affinity component, respectively. Of the cDNA-expressed P450 s tested, CYP2B6, CYP2C8, CYP2D6, and CYP3A4 catalyzed LOP N-demethylation. LOP N-demethylation was significantly inhibited when coincubated with quercetin (a CYP2C8 inhibitor) and ketoconazole (a CYP3A4 inhibitor) by 40 and 90%, respectively, but other chemical inhibitors tested showed weak or no significant inhibition. DLOP formation was highly correlated with CYP3A4-catalyzed midazolam 1-hydroxylation (rs=0.829; P<0.01), CYP2B6-catalzyed 7-ethoxy-4-trifluoromethylcoumarin O-deethylation (rs=0.691; P<0.05), and CYP2C8-catalyzed paclitaxel 6alpha-hydroxylation (rs=0.797; P<0.05). CYP2B6, CYP2C8, CYP2D6, and CYP3A4 catalyze LOP N-demethylation in human liver microsomes, and among them, CYP2C8 and CYP3A4 may play a crucial role in LOP metabolism at the therapeutic concentrations of LOP. Coadministration of these P450 inhibitors may cause drug

  6. High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs.

    PubMed

    Zhao, Zeping; Barcus, Matthew; Kim, Jonggun; Lum, Krystal L; Mills, Courtney; Lei, Xin Gen

    2016-09-01

    Prolonged high intakes of dietary selenium have been shown to induce gestational diabetes in rats and hyperinsulinemia in pigs. Two experiments were conducted to explore metabolic and molecular mechanisms for the diabetogenic potential of high dietary selenium intakes in pigs. In Expt. 1, 16 Yorkshire-Landrace-Hampshire crossbred pigs (3 wk old, body weight = 7.5 ± 0.81 kg, 50% males and 50% females) were fed a corn-soybean meal basal diet supplemented with 0.3 or 1.0 mg Se/kg (as selenium-enriched yeast for 6 wk). In Expt. 2, 12 pigs of the same crossbreed (6 wk old, body weight = 16.0 ± 1.8 kg) were fed a similar basal diet supplemented with 0.3 or 3.0 mg Se/kg for 11 wk. Biochemical and gene and protein expression profiles of lipid and protein metabolism and selenoproteins in plasma, liver, muscle, and adipose tissues were analyzed. In Expt. 1, the 1-mg-Se/kg diet did not affect body weight or plasma concentrations of glucose and nonesterified fatty acids. In Expt. 2, the 3-mg-Se/kg diet, compared with the 0.3-mg-Se/kg diet, increased (P < 0.05) concentrations of plasma insulin (0.2 compared with 0.4 ng/mL), liver and adipose lipids (41% to 2.4-fold), and liver and muscle protein (10-14%). In liver, the 3-mg-Se/kg diet upregulated (P < 0.05) the expression, activity, or both of key factors related to gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK); 13%], lipogenesis [sterol regulatory element binding protein 1 (SREBP1), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FASN); 46-90%], protein synthesis [insulin receptor (INSR), P70 ribosomal protein S6 kinase (P70), and phosphorylated ribosomal protein S6 (P-S6); 88-105%], energy metabolism [AMP-activated protein kinase (AMPK); up to 2.8-fold], and selenoprotein glutathione peroxidase 3 (GPX3; 1.4-fold) and suppressed (P < 0.05) mRNA levels of lipolysis gene cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1; 88%) and selenoprotein gene selenoprotein W1 (SEPW1; 46%). In muscle

  7. Insulin Therapy Improves Adeno-Associated Virus Transduction of Liver and Skeletal Muscle in Mice and Cultured Cells.

    PubMed

    Carrig, Sean; Bijjiga, Enoch; Wopat, Mitchell J; Martino, Ashley T

    2016-11-01

    Adeno-associated virus (AAV) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions, that is, α1-antitrypsin (AAT) disorder and hemophilia B. Exploring approaches that enhance transduction of liver and skeletal muscle, using these vectors, is beneficial for gene therapy. Regulating hormones as an approach to improve AAV transduction is largely unexplored. In this study we tested whether insulin therapy improves liver and skeletal muscle gene transfer. In vitro studies demonstrated that the temporary coadministration (2, 8, and 24 hr) of insulin significantly improves AAV2-CMV-LacZ transduction of cultured liver cells and differentiated myofibers, but not of lung cells. In addition, there was a dose response related to this improved transduction. Interestingly, when insulin was not coadministered with the virus but given 24 hr afterward, there was no increase in the transgene product. Insulin receptor gene (INSR) expression levels were increased 5- to 13-fold in cultured liver cells and differentiated myofibers when compared with lung cells. Similar INSR gene expression profiles occurred in mouse tissues. Insulin therapy was performed in mice, using a subcutaneously implanted insulin pellet or a high-carbohydrate diet. Insulin treatment began just before intramuscular delivery of AAV1-CMV-schFIX or liver-directed delivery of AAV8-CMV-schFIX and continued for 28 days. Both insulin augmentation therapies improved skeletal muscle- and liver-directed gene transduction in mice as seen by a 3.0- to 4.5-fold increase in human factor IX (hFIX) levels. The improvement was observed even after the insulin therapy ended. Monitoring insulin showed that insulin levels increased during the brief period of rAAV delivery and during the entire insulin augmentation period (28 days). This study demonstrates

  8. Skeletal muscle IL-6 and regulation of liver metabolism during high-fat diet and exercise training.

    PubMed

    Knudsen, Jakob G; Joensen, Ella; Bertholdt, Lærke; Jessen, Henrik; van Hauen, Line; Hidalgo, Juan; Pilegaard, Henriette

    2016-05-01

    Interleukin (IL)-6 is released from skeletal muscle (SkM) during exercise and has been shown to affect hepatic metabolism. It is, however, unknown whether SkM IL-6 is involved in the regulation of exercise training-induced counteraction of changes in carbohydrate and lipid metabolism in the liver in response to high-fat diet (HFD) feeding. Male SkM-specific IL-6 KO (MKO) and Floxed mice were subjected to Chow diet, HFD or HFD combined with exercise training (HFD ExTr) for 16 weeks. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) protein content decreased with both HFD and HFD ExTr in Floxed mice, but increased in IL-6 MKO mice on HFD In addition, the intrahepatic glucose concentration was in IL-6 MKO mice higher in HFD than chow. Within HFD ExTr mice, hepatic glucose-6-phosphatase (G6Pase) 36 kDa protein content was higher in IL-6 MKO than Floxed mice. Hepatic pyruvate dehydrogenase kinase (PDK) 4 and PDK2 protein content was in Floxed mice lower in HFD ExTr than Chow. In addition, hepatic ACC1-phosphorylation was higher and ACC1 protein lower in HFD Together this suggests that SkM IL-6 regulates hepatic glucose metabolism, but does not seem to be of major importance for the regulation of oxidative capacity or lipogenesis in liver during HFD or HFD combined with exercise training. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  9. Isolated lateral rectus muscle involvement as a presenting sign of euthyroid Graves disease.

    PubMed

    Erdurmus, Mesut; Celebi, Serdal; Ozmen, Sedat; Bucak, Yasin Y

    2011-08-01

    A 27-year-old man who presented with diplopia and proptosis and was diagnosed with euthyroid Graves disease and restrictive strabismus. It was determined that his symptoms were caused by isolated lateral rectus muscle involvement. Diplopia resolved and ocular motility improved substantially following 6 weeks of oral corticosteroid therapy. Copyright © 2011 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  10. Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4.

    PubMed

    Chesné, C; Guyomard, C; Guillouzo, A; Schmid, J; Ludwig, E; Sauter, T

    1998-01-01

    1. The metabolism of Meloxicam (ME) and the cytochrome(s) P450 (CYPs) involved were analysed by using primary human hepatocytes, human liver microsomes and microsomes from recombinant human B-lymphoblastoid cell lines. 2. While human hepatocytes were capable of converting ME to a 5-hydroxymethyl metabolite (M7) and then to a 5-carboxyderivative (M5), human liver microsomes formed mostly only the 5-hydroxymethylderivative. The kinetics of the formation of M7 by human liver microsomes were biphasic with Km = 13.6 +/- 9.5 and 381 +/- 55.2 microM respectively. The corresponding Vmax were 33.7 +/- 24.2 and 143 +/- 83.9 pmol/min/mg protein respectively. 3. CYP2C9 and, to a much lesser extent, CYP3A4 were found to convert ME to M7. The involvement of 2C9 was demonstrated by inhibition of tolbutamide hydroxylase activity in the presence of ME, inhibition of ME metabolism by sulphaphenazole, correlation between ME metabolism and tolbutamide hydroxylase activity and active metabolism of ME by recombinant 2C9. The involvement of 3A4 was shown by inhibition of ME metabolism by ketoconazole, correlation between ME metabolism and nifedipine oxidase activity and metabolism of ME by recombinant 3A4. Kinetics of the formation of M7 by the individual enzymes resulted in a Km = 9.6 microM and Vmax = 8.4 pmol/min/mg protein for 2C9 and a Km = 475 microM and Vmax = 23 pmol/min/mg protein for 3A4.

  11. Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver

    PubMed Central

    Guillén, Natalia; Navarro, María A.; Arnal, Carmen; Noone, Enda; Arbonés-Mainar, José M.; Acín, Sergio; Surra, Joaquín C.; Muniesa, Pedro; Roche, Helen M.; Osada, Jesús

    2009-01-01

    Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote fatty liver in mice, while cis-9, trans-11-CLA ameliorates this effect, suggesting regulation of multiple genes. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid isomers, and their hepatic gene expression was analyzed with DNA microarrays. To provide an initial screening of candidate genes, only 12 with remarkably modified expression between both CLA isomers were considered and confirmed by quantitative RT-PCR. Additionally mRNA expression of 15 genes involved in lipid metabolism was also studied. Ten genes (Fsp27, Aqp4, Cd36, Ly6d, Scd1, Hsd3b5, Syt1, Cyp7b1, and Tff3) showed significant associations among their expressions and the degree of hepatic steatosis. Their involvement was also analyzed in other models of steatosis. In hyperhomocysteinemic mice lacking Cbs gene, only Fsp27, Cd36, Scd1, Syt1, and Hsd3b5 hepatic expressions were associated with steatosis. In apoE-deficient mice consuming olive-enriched diet displaying reduction of the fatty liver, only Fsp27 and Syt1 expressions were found associated. Using this strategy, we have shown that expression of these genes is highly associated with hepatic steatosis in a genetic disease such as Cbs deficiency and in two common situations such as Western diets containing CLA isomers or a Mediterranean-type diet. Conclusion: The results highlight new processes involved in lipid handling in liver and will help to understand the complex human pathology providing new proteins and new strategies to cope with hepatic steatosis. PMID:19258494

  12. Case report: Severe hematological, muscle and liver toxicity caused by drugs and artichoke infusion interaction in an elderly polymedicated patient.

    PubMed

    Campos, M G; Machado, J; Costa, M L; Lino, S; Correia, F; Maltez, F

    2017-09-12

    Case report, in a patient with a history of diabetes and hypertension, treated with metformin, gliclazide, enalapril + hydrochlorothiazide, amlodipine, aspirin and diazepam, recently medicated for a gouty crisis with colchicine and clonixin without improvement. Believing it could help in the treatment of gouty crisis symptoms he took about 1.5 L of artichoke infusion (Cynara cardunculus). He felt better and did agriculture work but developed a distal muscle pain, severe anemia, standard biochemical liver cholestasis, increase of alkaline phosphatase and marked increase of inflammatory parameters (hyperleucocytosis) and enters in the emergency department at the hospital. The prominence of the inflammatory parameters was ruled out because of exhaustive autoimmune, infectious or para-neoplastic syndrome (blood cultures, serology, diagnostic imaging, bone marrow and bone biopsy, muscle biopsy and nerve, abdominal angiography) were carried out showing normal results. The evaluation pointed out that the concomitant intake of artichoke infusion may have been involved in the framework developed, since the drugs which were being administered to/by the patient have a metabolism mainly mediated by CYP450 3A4 and 2C9 that could be compromised when these isoenzymes are inhibited by phenolic and flavonoid compounds from plants. Colchicine was one of the last drugs took that have as side effects most of the symptoms felt by patient including diarrhea and anemia. The spontaneous and complete recovery of the patient and the negativity of research looking for other causes, conduce to a strong possibility of the interaction between artichoke and the drugs in the clinical presentation of this case. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers.

    PubMed

    Andrade, Luis Jesuino de Oliveira; Melo, Paulo Roberto Santana de; Atta, Ajax Mercês; Atta, Maria Luiza Brito de Sousa; Jesus, Larissa Santana de; Sousa, Gabriel Menezes de; Silva, Carolina Alves Costa; Paraná, Raymundo

    2011-01-01

    Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8% and cryoglobulinemia was demonstrated in 36.9% patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

  14. Statin adverse effects: patients' experiences and laboratory monitoring of muscle and liver injuries.

    PubMed

    Chaipichit, Nataporn; Krska, Janet; Pratipanawatr, Thongchai; Jarernsiripornkul, Narumol

    2015-04-01

    Although statins have great benefit on the prevention of cardiovascular diseases with limited adverse effects (AEs), little is known about patients' contribution of AE reports in clinical practice. To explore patients' experiences of statin AEs and related laboratory monitoring in clinical practice. Outpatient clinics of two University hospitals in northeast Thailand. Generic symptom checklist questionnaires for self-reporting AEs were distributed to patients prescribed simvastatin, atorvastatin, or rosuvastatin at outpatient clinics. Clinical information was obtained from medical records. Reported symptoms were assessed for causality considering previously known statin AEs, concomitant diseases and drugs. Potential statin AEs reported by patients and monitoring of laboratory parameters related to musculoskeletal and liver disorders. Of the total 718 valid responses, 76.0 % of patients reported at least one symptom, most of which (69.0 %) were probable/possible statin AEs. Musculoskeletal and liver-related symptoms were reported by 283 (39.4 %) and 134 patients (18.7 %), respectively. Probable/possible AEs were categorized in 56.7 % of their musculoskeletal and gastrointestinal symptoms. Majority of patients had at least one laboratory test on initiation of (64.8 %) and during statin treatment (61.8 %). Patients taking atorvastatin or rosuvastatin, and patients with history of chronic renal diseases were more likely to have creatine kinase (CK) monitored on initiation of and during statin treatment. Additionally, taking drugs which could potentially increase muscle injury (OR 1.929, P < 0.01) and self-reporting of musculoskeletal symptoms (OR 1.805, P < 0.01) were associated with CK monitoring during statin treatment. Reporters of musculoskeletal symptoms also had significantly higher mean CK level than those not reporting any musculoskeletal symptoms (207.35 ± 155.40 vs. 143.95 ± 83.07 U/L, respectively; P = 0.037). Patient reporting of liver AEs was not related

  15. Autophagy-lysosomal pathway is involved in lipid degradation in rat liver.

    PubMed

    Skop, V; Cahová, M; Papáčková, Z; Páleníčková, E; Daňková, H; Baranowski, M; Zabielski, P; Zdychová, J; Zídková, J; Kazdová, L

    2012-01-01

    We present data supporting the hypothesis that the lysosomal-autophagy pathway is involved in the degradation of intracellular triacylglycerols in the liver. In primary hepatocytes cultivated in the absence of exogenous fatty acids (FFA), both inhibition of autophagy flux (asparagine) or lysosomal activity (chloroquine) decreased secretion of VLDL (very low density lipoproteins) and formation of FFA oxidative products while the stimulation of autophagy by rapamycine increased some of these parameters. Effect of rapamycine was completely abolished by inactivation of lysosomes. Similarly, when autophagic activity was influenced by cultivating the hepatocytes in "starving" (amino-acid poor medium) or "fed" (serum-supplemented medium) conditions, VLDL secretion and FFA oxidation mirrored the changes in autophagy being higher in starvation and lower in fed state. Autophagy inhibition as well as lysosomal inactivation depressed FFA and DAG (diacylglycerol) formation in liver slices in vitro. In vivo, intensity of lysosomal lipid degradation depends on the formation of autophagolysosomes, i.e. structures bringing the substrate for degradation and lysosomal enzymes into contact. We demonstrated that lysosomal lipase (LAL) activity in liver autophagolysosomal fraction was up-regulated in fasting and down-regulated in fed state together with the increased translocation of LAL and LAMP2 proteins from lysosomal pool to this fraction. Changes in autophagy intensity (LC3-II/LC3-I ratio) followed a similar pattern.

  16. Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism.

    PubMed

    Liao, Wenjuan; Liu, Hongbing; Zhang, Yiwei; Jung, Ji Hoon; Chen, Jiaxiang; Su, Xiaohua; Kim, Yeong C; Flores, Elsa R; Wang, San Ming; Czarny-Ratajczak, Malwina; Li, Wen; Zeng, Shelya X; Lu, Hua

    2017-08-21

    TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.

  17. Abdominal angiostrongyliasis with involvement of liver histopathologically confirmed: a case report.

    PubMed

    Quirós, José Luis; Jiménez, Ernesto; Bonilla, Raúl; Arce, Isabel; Hernández, Cristian; Jiménez, Yendry

    2011-01-01

    Human abdominal angiostrongyliasis is a zoonotic disease caused by ingestion of the L3 larvae of Angiostrongylus costaricensis. The human infection gives rise to a pathological condition characterized by acute abdominal pain, secondary to an inflammatory granulomatous reaction, marked eosinophilia and eosinophilic vasculitis. Most commonly this disease is limited to intestinal location, primary ileocecal, affecting the mesenteric arterial branches and intestinal walls. We present one of the few cases reported around the world with simultaneous involvement of the intestines and liver, including proved presence of nematodes inside the hepatic arteriole.

  18. Phospholipase D1 is involved in α1-adrenergic contraction of murine vascular smooth muscle.

    PubMed

    Wegener, Jörg W; Loga, Florian; Stegner, David; Nieswandt, Bernhard; Hofmann, Franz

    2014-03-01

    α1-Adrenergic stimulation increases blood vessel tone in mammals. This process involves a number of intracellular signaling pathways that include signaling via phospholipase C, diacylglycerol (DAG), and protein kinase C. So far, it is not certain whether signaling via phospholipase D (PLD) and PLD-derived DAG is involved in this process. We asked whether PLD participates in the α1-adrenergic-mediated signaling in vascular smooth muscle. α1-Adrenergic-induced contraction was assessed by myography of isolated aortic rings and by pressure recordings using the hindlimb perfusion model in mice. The effects of the PLD inhibitor 1-butanol (IC50 0.15 vol%) and the inactive congener 2-butanol were comparatively studied. Inhibition of PLD by 1-butanol reduced specifically the α1-adrenergic-induced contraction and the α1-adrenergic-induced pressure increase by 10 and 40% of the maximum, respectively. 1-Butanol did not influence the aortic contractions induced by high extracellular potassium, by the thromboxane analog U46619, or by a phorbol ester. The effects of 1-butanol were absent in mice that lack PLD1 (Pld1(-/-) mice) or that selectively lack the CaV1.2 channel in smooth muscle (sm-CaV1.2(-/-) mice) but still present in the heterozygous control mice. α1-Adrenergic contraction of vascular smooth muscle involves activation of PLD1, which controls a portion of the α1-adrenergic-induced CaV1.2 channel activity.

  19. Involvement of central and peripheral cannabinoid receptors on antinociceptive effect of tetrahydrocannabinol in muscle pain.

    PubMed

    Bagüés, Ana; Martín, M Isabel; Sánchez-Robles, Eva M

    2014-12-15

    Cannabinoid (CB) receptors have emerged as an attractive therapeutic target for pain management in recent years and the interest in the use of cannabinoids is gradually increasing, particularly in patients where conventional treatments fail. Muscle pain is a major clinical problem and new pharmacological approaches are being studied. Recently, we have demonstrated that cannabinoid synthetic agonists are useful to reduce muscular pain in two animal models, where the local administration is effective. Now, we want to know if tetrahydrocannabinol (THC), a cannabinoid natural derivative with therapeutic use in humans, is also effective in reducing acute muscle pain. The antinociceptive effect of THC by systemic (i.p.) and local (i.m.) administration was tested in two animal models of acute muscle pain, rat masseter and gastrocnemius, induced by hypertonic saline (HS) injection. The drugs used were the non-selective agonist THC and two selective cannabinoid antagonists, AM251 (CB1) and AM630 (CB2). THC, i.p. and i.m. administered, reduced the nociceptive behaviours induced by HS in both muscular pain models. The antinociceptive effect induced by the systemic administration of THC was mediated by CB1 receptors in the masseter muscle whereas in gastrocnemius both CB1 and CB2 receptors participated. When THC was administered locally, only CB2 receptors were involved in the antinociceptive effect in both muscles. This study suggests that THC could be a future pharmacological option in the treatment of muscle pain. The local administration of THC could be an interesting option to treat this type of pain avoiding the central adverse effects.

  20. Insulin-induced hypoglycaemia is co-ordinately regulated by liver and muscle during acute and chronic insulin stimulation in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Polakof, Sergio; Skiba-Cassy, Sandrine; Choubert, Georges; Panserat, Stéphane

    2010-05-01

    The relative glucose intolerance of carnivorous fish species is often proposed to be a result of poor peripheral insulin action or possibly insulin resistance. In the present study, data from aortic cannulated rainbow trout receiving bovine insulin (75 mIU kg(-1)) injections show for the first time their ability to clear glucose in a very efficient manner. In another set of experiments, mRNA transcripts and protein phosphorylation status of proteins controlling glycaemia and glucose-related metabolism were studied during both acute and chronic treatment with bovine insulin. Our results show that fasted rainbow trout are well adapted at the molecular level to respond to increases in circulating insulin levels, and that this hormone is able to potentially improve glucose distribution and uptake by peripheral tissues. After acute insulin administration we found that to counter-regulate the insulin-induced hypoglycaemia, trout metabolism is strongly modified. This short-term, efficient response to hypoglycaemia includes a rapid, coordinated response involving the reorganization of muscle and liver metabolism. During chronic insulin treatment some of the functions traditionally attributed to insulin actions in mammals were observed, including increased mRNA levels of glucose transporters and glycogen storage (primarily in the muscle) as well as decreased mRNA levels of enzymes involved in de novo glucose production (in the liver). Finally, we show that the rainbow trout demonstrates most of the classic metabolic adjustments employed by mammals to efficiently utilize glucose in the appropriate insulin context.

  1. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

    SciTech Connect

    Bull, R.J.; Thrall, B.D.; Sasser, L.B.; Miller, J.H.; Schultz, I.R.

    1998-06-01

    'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold

  2. Effects of thyme as a feed additive in broiler chickens on thymol in gut contents, blood plasma, liver and muscle.

    PubMed

    Haselmeyer, Alexander; Zentek, Jürgen; Chizzola, Remigius

    2015-02-01

    Aromatic herbs as feed additives in animal production are encountering growing interest, but data on the fate of the aromatic compounds from the plant in the animal body are very scarce. In the present study, thyme (Thymus vulgaris) herb consisting of leaves and flowers without stems was used as an ingredient in the diet for broilers. The herb was fed for 35 days to five groups of broilers (0, 0.1, 0.2, 0.3, and 1% w/w in the diet). Animal performance and the concentrations of the main essential oil component from thyme, thymol, were measured in gut contents, plasma and liver and muscle tissues using solid phase microextraction and gas chromatography/mass spectrometry. There were no differences between the groups in feed intake, daily weight gain, feed conversion and slaughter weight. Thymol was detected in gut contents, plasma and liver and muscle tissues. Increased intestinal thymol concentrations were found in the group with 1% thyme compared with the other groups (P < 0.05). In liver and muscle tissues the thymol levels were close to the limit of quantification. The data do not indicate a positive effect of thyme on animal performance. With high dietary levels of thyme herb, thymol concentrations increased in gut contents and plasma but were very low in edible tissues such as liver and flesh. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

  3. Occurrence, Distribution, and Risk Assessment of Perfluoroalkyl Acids (PFAAs) in Muscle and Liver of Cattle in Xinjiang, China.

    PubMed

    Wang, Gehui; Lu, Jianjiang; Xing, Zhenni; Li, Shanman; Liu, Zilong; Tong, Yanbin

    2017-08-28

    Despite risks associated with perfluoroalkyl acids (PFAAs) in many regions, little is known about their prevalence in Xinjiang. We determined the presence of 13 PFAAs in 293 beef muscle and liver samples collected in 22 cities covering northern, southern, and eastern Xinjiang using liquid chromatography, coupled with tandem mass spectrometry. Overall, the average values for PFAAs were relatively low compared with previous studies. Liver presented higher mean levels of total PFAAs at 1.632 ng/g, which was over 60-fold higher than in muscle (0.026 ng/g). Among the PFAAs analyzed, medium-chain compounds were dominant, accounting for more than 70% of the total. Perfluorooctane sulfonate (PFOS) was highly prevalent in the liver with the highest mean concentration (0.617 ng/g) and detection frequency (80%). When comparing the three regions of Xinjiang, we found differences in PFAA profiles, with the northern region showing the highest levels. Furthermore, the average daily intake and hazard ratios of PFOS and perfluorooctanoic acid varied by region, urban/rural environment, gender, ethnicity, and age. The highest risk value of 13 PFAAs was estimated to be 0.837 × 10(-3), which is far below 1, indicating that there is no health risk posed by eating beef muscle and liver in Xinjiang.

  4. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM

    SciTech Connect

    Mitrakou, A.; Kelley, D.; Veneman, T.; Jenssen, T.; Pangburn, T.; Reilly, J.; Gerich, J. )

    1990-11-01

    To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with (14C)glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2. In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects, but glucose Rd was not significantly different in NIDDM and nondiabetic subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.

  5. Proteomic profile of carbonylated proteins in rat liver: exercise attenuated oxidative stress may be involved in fatty liver improvement.

    PubMed

    Hu, Xiaofei; Duan, Zhigui; Hu, Hui; Li, Guolin; Yan, Siyu; Wu, Jinfeng; Wang, Jun; Yin, Dazhong; Xie, Qingji

    2013-05-01

    To screen target proteins of oxidative stress which mediate the effects of exercise on preventing nonalcoholic fatty liver disease (NAFLD), the methods for selecting carbonylated proteins were modified, and carbonylated proteins were profiled. The results showed that treadmill training reduced oxidative stress and the levels of intrahepatic triglyceride (IHTG). The changes in IHTG showed a significant positive correlation with oxidative stress as indicated by malondialdehyde level. Further results from proteomics illustrated that 17 functional proteins were susceptible to oxidative modification, and exercise protected three proteins from carbonylation. The latter three proteins may serve as both direct target proteins of oxidative stress and mediators contributing to the beneficial effects of exercise. In particular, a long-chain specific acyl-CoA dehydrogenase (ACADL) which was a key enzyme in lipid metabolism was not carbonylated and with higher activities in exercise group. These findings indicate that this modified technique is practical and powerful in selecting carbonylated proteins. Long-term treadmill training is effective in ameliorating oxidative stress and preventing the accumulation of IHTG. Among the 17 target proteins of oxidative modification, three proteins contribute to the beneficial effects of exercise. Preventing ACADL from carbonylation may be involved in the physiological mechanism of exercise-induced NAFLD improvement.

  6. Accumulation of trace metals in the muscle and liver tissues of five fish species from the Persian Gulf.

    PubMed

    Agah, Homira; Leermakers, Martine; Elskens, Marc; Fatemi, S Mohamad Rez; Baeyens, Willy

    2009-10-01

    In this study, concentrations of 16 elements were quantified in muscles and livers of 141 fishes belonging to five commercially species. It was also our intention to evaluate potential risks to human health associated with seafood consumption. The grunt, flathead, greasy grouper, tiger-tooth croaker and silver pomfret fish species were obtained from Abadan, Deylam, Bushehr-Nirogah, Dayyer port, Lengeh port and Abbas port in Hormozgan, Bushehr and Khozesran provinces at the Iranian waters of the Persian Gulf. The contents of Al, As, Be, Cd, Cr, Co, Cu, Fe, Pb, Mn, Mo, Ni, Sb, Tl, V and Zn in fish muscles and livers were determined by Inductively Coupled Plasma Mass Spectrometry (ICP MS), after digestion in a CEM (Mars 5) microwave oven using nitric acid and hydrogen peroxide. Our results indicated that almost all metals were more accumulated in younger flathead, greasy grouper and tiger-tooth fishes. Contrary to the other fish species, grunt seems to stronger accumulating elements in the older fishes. Strong and positive correlations were observed in three or more of the fish species between V, Al, Fe, Tl, Co and Pb. The results confirmed that fish muscle and liver tissues appeared to be good bio-indicators for identification of coastal areas exposed to metallic contaminants. The results also showed that the element levels in the muscles of all fishes in our study were lower than the maximum allowable concentrations and pose no threat to public health, except for arsenic.

  7. Total mercury in muscles and liver of Mugil spp. from three coastal lagoons of NW Mexico: concentrations and risk assessment.

    PubMed

    Delgado-Alvarez, C G; Frías-Espericueta, M G; Ruelas-Inzunza, J; Becerra-Álvarez, M J; Osuna-Martínez, C C; Aguilar-Juárez, M; Osuna-López, J I; Escobar-Sánchez, O; Voltolina, D

    2017-07-01

    Total mercury (Hg) concentrations were determined by atomic absorption spectrophotometry in muscles and liver of composite samples of Mugil cephalus and M. curema collected during November 2013 and in January, April, and July 2014 from the coastal lagoons Altata-Ensenada del Pabellón (AEP), Ceuta (CEU), and Teacapán-Agua Brava (TAG) of Sinaloa State. The mean Hg contents and information on local consumption were used to assess the possible risk caused by fish ingestion. Mean total mercury levels in the muscles ranged from 0.11 to 0.39 μg/g, while the range for liver was 0.12-3.91 μg/g. The mean Hg content of the liver was significantly (p < 0.001) higher than that of the muscles only in samples collected from AEP. Although total Hg levels in the muscles were lower than the official permissible limit, the HQ values for methyl mercury calculated for the younger age classes of one fishing community were >1, indicating a possible risk for some fishing communities of the Mexican Pacific coast.

  8. Comparison of mercury concentrations in liver, muscle, whole bodies, and composites of fish from the Red River of the North

    USGS Publications Warehouse

    Goldstein, Robert M.; Brigham, Mark E.; Stauffer, Joseph C.

    1996-01-01

    Carp (Cyprinus carpio) from four sites and channel catfish (Ictalurus punctatus) from one site in the Red River of the North in 1994 were analyzed for total mercury content. In carp, mercury concentrations differed among liver, muscle, and whole bodies (0.11, 0.31, and 0.18 µg/g wet weight, respectively), between large and small size groups, but not location. Mercury distribution in channel catfish tissues differed from that in carp. Liver and muscle tissue had similar mean concentrations; each was higher than whole-body concentrations (0.16, 0.18, and 0.11 µg/g, respectively). Mercury concentrations were not significantly different between the two size groups of channel catfish. Weighted-mean mercury concentrations from seven individual fish agreed closely (usually within 10%) with concentrations determined on physical composites of the same fish. The ratio of mercury in whole bodies to mercury in muscle was similar for both carp and channel catfish. Historical data indicate that this ratio may be applicable to other species and locations. The ratio of mercury in livers to whole bodies and muscle differed between carp and channel catfish, which may reflect physiological differences between different trophic groups.

  9. Intensive insulin treatment induces insulin resistance in diabetic rats by impairing glucose metabolism-related mechanisms in muscle and liver.

    PubMed

    Okamoto, Maristela Mitiko; Anhê, Gabriel Forato; Sabino-Silva, Robinson; Marques, Milano Felipe dos Santos Ferreira; Freitas, Helayne Soares; Mori, Rosana Cristina Tieko; Melo, Karla Fabiana S; Machado, Ubiratan Fabres

    2011-10-01

    Insulin replacement is the only effective therapy to manage hyperglycemia in type 1 diabetes mellitus (T1DM). Nevertheless, intensive insulin therapy has inadvertently led to insulin resistance. This study investigates mechanisms involved in the insulin resistance induced by hyperinsulinization. Wistar rats were rendered diabetic by alloxan injection, and 2 weeks later received saline or different doses of neutral protamine Hagedorn insulin (1.5, 3, 6, and 9 U/day) over 7 days. Insulinopenic-untreated rats and 6U- and 9U-treated rats developed insulin resistance, whereas 3U-treated rats revealed the highest grade of insulin sensitivity, but did not achieve good glycemic control as 6U- and 9U-treated rats did. This insulin sensitivity profile was in agreement with glucose transporter 4 expression and translocation in skeletal muscle, and insulin signaling, phosphoenolpyruvate carboxykinase/glucose-6-phosphatase expression and glycogen storage in the liver. Under the expectation that insulin resistance develops in hyperinsulinized diabetic patients, we believe insulin sensitizer approaches should be considered in treating T1DM.

  10. Molecular characterization of argininosuccinate synthase and argininosuccinate lyase from the liver of the African lungfish Protopterus annectens, and their mRNA expression levels in the liver, kidney, brain and skeletal muscle during aestivation.

    PubMed

    Chng, You R; Ong, Jasmine L Y; Ching, Biyun; Chen, Xiu L; Wong, Wai P; Chew, Shit F; Ip, Yuen K

    2014-10-01

    Argininosuccinate synthase (Ass) and argininosuccinate lyase (Asl) are involved in arginine synthesis for various purposes. The complete cDNA coding sequences of ass and asl from the liver of Protopterus annectens consisted of 1,296 and 1,398 bp, respectively. Phylogenetic analyses revealed that the deduced Ass and Asl of P. annectens had close relationship with that of the cartilaginous fish Callorhinchus milii. Besides being strongly expressed in the liver, ass and asl expression were detectable in many tissues/organs. In the liver, mRNA expression levels of ass and asl increased significantly during the induction phase of aestivation, probably to increase arginine production to support increased urea synthesis. The increases in ass and asl mRNA expression levels during the prolonged maintenance phase and early arousal phase of aestivation could reflect increased demand on arginine for nitric oxide (NO) production in the liver. In the kidney, there was a significant decrease in ass mRNA expression level after 6 months of aestivation, indicating possible decreases in the synthesis and supply of arginine to other tissues/organs. In the brain, changes in ass and asl mRNA expression levels during the three phases of aestivation could be related to the supply of arginine for NO synthesis in response to conditions that resemble ischaemia and ischaemia-reperfusion during the maintenance and arousal phase of aestivation, respectively. The decrease in ass mRNA expression level, accompanied with decreases in the concentrations of arginine and NO, in the skeletal muscle of aestivating P. annectens might ameliorate the potential of disuse muscle atrophy.

  11. Effects of short-term growth hormone treatment on liver and muscle transcriptomes in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Gahr, Scott A; Vallejo, Roger L; Weber, Gregory M; Shepherd, Brian S; Silverstein, Jeffrey T; Rexroad, Caird E

    2008-02-19

    Although studies have established that exogenous growth hormone (GH) treatment stimulates growth in fish, its effects on target tissue gene expression are not well characterized. We assessed the effects of Posilac (Monsanto, St. Louis, MO), a recombinant bovine GH, on tissue transcript levels in rainbow trout selected from two high-growth rate and two low-growth rate families. Transcript abundance was measured in liver and muscle with the Genome Research in Atlantic Salmon Project (GRASP) 16K cDNA microarray. A selection of the genes identified as altered by the microarray and transcripts for insulin-like growth factors, growth hormone receptors (GHRs), and myostatins were measured by real-time PCR in the liver, muscle, brain, kidney, intestine, stomach, gill, and heart. In general, transcripts identified as differentially regulated in the muscle on the microarray showed similar directional changes of expression in the other nonhepatic tissues. A total of 114 and 66 transcripts were identified by microarray as differentially expressed with GH treatment across growth rate for muscle and liver, respectively. The largest proportion of these transcripts represented novel transcripts, followed by immune and metabolism-related genes. We have identified a number of genes related to lipid metabolism, supporting a modulation in lipid metabolism following GH treatment. Most notable among the growth-axis genes measured by real-time PCR were increases in GHR1 and -2 transcripts in liver and muscle. Our results indicate that short-term GH treatment activates the immune system, shifts the metabolic sectors, and modulates growth-regulating genes.

  12. The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells.

    PubMed

    Dressel, Uwe; Allen, Tamara L; Pippal, Jyotsna B; Rohde, Paul R; Lau, Patrick; Muscat, George E O

    2003-12-01

    Lipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. In vitro and in vivo genetic and pharmacological studies have demonstrated PPARalpha regulates lipid catabolism. In contrast, PPARgamma regulates the conflicting process of lipid storage. However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. PPARbeta/delta, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Consequently, it has a significant role in insulin sensitivity, the blood-lipid profile, and lipid homeostasis. Surprisingly, the role of PPARbeta/delta in skeletal muscle has not been investigated. We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARgamma induces gene expression associated with glucose uptake, fatty acid

  13. Depletion of selenium in blood, liver and muscle from beef heifers previously fed forages containing high levels of selenium.

    PubMed

    Benes, Sharon E; Robinson, Peter H; Cun, Grace S

    2015-12-01

    Beef heifers which had grazed 'Jose' tall wheatgrass (TWG; Thinopyrum ponticum var. 'Jose'; 10 heifers) and creeping wildrye (CWR; Leymus triticoides var. 'Rio'; 10 heifers) with high levels of Se (>2 mg/kg DM) due to growth in saline soils, accumulated high Se levels in blood, liver and muscle (Juchem et al., 2012). We determined the decrease in Se levels in blood, liver and muscle from these heifers, particularly the decrease of Se in muscle, in order to determine the maximum feeding length of a low Se diet (LSeD) required sustaining Se-enriched beef. Immediately after grazing, all heifers were fed a LSeD containing <0.30 mg/kg DM for 209 d. Blood, liver and muscle samples, as well as body weight (BW), were collected at the beginning and end of the LSeD feeding period and at intermediate times. After grazing, CWR and TWG heifers had similar BW, but TWG heifers had higher levels of Se in whole blood (1.19 versus 0.81 mg/L), liver (2.67 versus 2.12 mg/kg wet weight (WW)), and muscle tissue (0.87 versus 0.63 mg/kg WW) than CWR heifers. The Se levels decreased with exposure time to the LSeD and, at 82 d of feeding the LSeD, Se levels were 77 (liver), 49 (blood) and 31% (muscle) lower. The BW gains for both groups were ~0.5 kg/d during the first 82 d of feeding, but increased thereafter. Levels of Cu in serum (0.28 versus 0.50 mg/L) and liver (1.14 versus 22.9 mg/kg WW) were lower at the end of grazing in TWG heifers, and suggested a potential Cu deficiency. Grazing forages with high Se levels can result in Se-enriched beef, but a LSeD feeding period of <82 d is required to maintain enrichment.

  14. Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets

    NASA Astrophysics Data System (ADS)

    Brackmann, Christian; Gabrielsson, Britt; Svedberg, Fredrik; Holmäng, Agneta; Sandberg, Ann-Sofie; Enejder, Annika

    2010-11-01

    Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.

  15. Molecular Mechanisms Involved in the Interaction Effects of Alcohol and Hepatitis C Virus in Liver Cirrhosis

    PubMed Central

    Mas, Valeria R; Fassnacht, Ryan; Archer, Kellie J; Maluf, Daniel

    2010-01-01

    The mechanisms by which alcohol consumption accelerates liver disease in patients with chronic hepatitis C virus (HCV) are not well understood. To identify the characteristics of molecular pathways affected by alcohol in HCV patients, we fit probe-set level linear models that included the additive effects as well as the interaction between alcohol and HCV. The study included liver tissue samples from 78 patients, 23 (29.5%) with HCV-cirrhosis, 13 (16.7%) with alcohol-cirrhosis, 23 (29.5%) with HCV/alcohol cirrhosis and 19 (24.4%) with no liver disease (no HCV/no alcohol group). We performed gene-expression profiling by using microarrays. Probe-set expression summaries were calculated by using the robust multiarray average. Probe-set level linear models were fit where probe-set expression was modeled by HCV status, alcohol status, and the interaction between HCV and alcohol. We found that 2172 probe sets (1895 genes) were differentially expressed between HCV cirrhosis versus alcoholic cirrhosis groups. Genes involved in the virus response and the immune response were the more important upregulated genes in HCV cirrhosis. Genes involved in apoptosis regulation were also overexpressed in HCV cirrhosis. Genes of the cytochrome P450 superfamily of enzymes were upregulated in alcoholic cirrhosis, and 1230 probe sets (1051 genes) had a significant interaction estimate. Cell death and cellular growth and proliferation were affected by the interaction between HCV and alcohol. Immune response and response to the virus genes were downregulated in HCV-alcohol interaction (interaction term alcohol*HCV). Alcohol*HCV in the cirrhotic tissues resulted in a strong negative regulation of the apoptosis pattern with concomitant positive regulation of cellular division and proliferation. PMID:20386865

  16. Polarized electric field effects on the regulation of succinate dehydrogenase activity in amphibian muscle and liver: kinetic study.

    PubMed

    Subrahamanyam, K; Reddy, G R; Babu, G R; Chetty, C S

    1989-04-01

    Electropolarity treatment (0.8 V/DC/Cm) was given to the gastrocnemius muscle of Bufo melanostictus every day for 5 min. for 5 days, and kinetic study of succinate dehydrogenase (SDH) in muscle and liver was conducted with different effectors - sodium malonate, ethylene diamine tetra acetic acid (EDTA), calcium chloride (CACl2) and sodium citrate. Of the four modulators tested, the malonate and EDTA inhibited while sodium citrate and CACl2 activated the enzyme. The significance of the modulation in SDH activity to different extents was discussed.

  17. Piezo1 in Smooth Muscle Cells Is Involved in Hypertension-Dependent Arterial Remodeling.

    PubMed

    Retailleau, Kevin; Duprat, Fabrice; Arhatte, Malika; Ranade, Sanjeev Sumant; Peyronnet, Rémi; Martins, Joana Raquel; Jodar, Martine; Moro, Céline; Offermanns, Stefan; Feng, Yuanyi; Demolombe, Sophie; Patel, Amanda; Honoré, Eric

    2015-11-10

    The mechanically activated non-selective cation channel Piezo1 is a determinant of vascular architecture during early development. Piezo1-deficient embryos die at midgestation with disorganized blood vessels. However, the role of stretch-activated ion channels (SACs) in arterial smooth muscle cells in the adult remains unknown. Here, we show that Piezo1 is highly expressed in myocytes of small-diameter arteries and that smooth-muscle-specific Piezo1 deletion fully impairs SAC activity. While Piezo1 is dispensable for the arterial myogenic tone, it is involved in the structural remodeling of small arteries. Increased Piezo1 opening has a trophic effect on resistance arteries, influencing both diameter and wall thickness in hypertension. Piezo1 mediates a rise in cytosolic calcium and stimulates activity of transglutaminases, cross-linking enzymes required for the remodeling of small arteries. In conclusion, we have established the connection between an early mechanosensitive process, involving Piezo1 in smooth muscle cells, and a clinically relevant arterial remodeling.

  18. Muscle involvement during intermittent contraction patterns with different target force feedback modes.

    PubMed

    Sjøgaard, G; Jørgensen, L V; Ekner, D; Søgaard, K

    2000-01-01

    Assess the effect of different feedback modes during intermittent contractions on primary and assessory muscle activity. Intermittent contractions and physiological responses have been studied in laboratory settings. However, the feedback given to the subjects regarding timing and force level is generally not specified. Repeated measure design in which six subjects in randomized order performed two experimental conditions only differing in feedback mode. Intermittent static elbow flexion was performed against either a fixed-force transducer (visual feedback) or a weight to be held in position (proprioceptive feedback) both corresponding to 30% maximal voluntary contraction. Contraction and relaxation timing of 6 and 4 s, respectively, was shown on a VDU screen as colour code identical in both conditions. Test contractions performed before and following 30 min of intermittent contractions showed larger fatigue development with proprioceptive feedback than visual feedback. Also rating of perceived exertion increased more during proprioceptive feedback than visual feedback. This may in part be explained by small differences in the mechanics during the two different feedback modes. In line with this, EMG recorded from four shoulder/arm muscles analyzed for amplitude and frequency showed similar activity initially; but later, during the 30 min contraction larger amplitudes were attained during proprioceptive feedback than visual feedback. Feedback mode significantly effects the muscle involvement and fatigue during intermittent contractions. RelevanceIntermittent contractions are common in many work places and various feedback modes are being given regarding work requirements. The choice of feedback may significantly affect the muscle load and consequently the development muscle fatigue and disorders.

  19. Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis.

    PubMed

    Chiba, Ko; Tsuchiya, Masahiro; Koide, Masashi; Hagiwara, Yoshihiro; Sasaki, Keiichi; Hattori, Yoshinori; Watanabe, Makoto; Sugawara, Shunji; Kanzaki, Makoto; Endo, Yasuo

    2015-01-01

    Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis.

  20. The involvement of transient receptor potential canonical type 1 in skeletal muscle regrowth after unloading‐induced atrophy

    PubMed Central

    Xia, Lu; Cheung, Kwok‐Kuen; Yeung, Simon S.

    2016-01-01

    Key points Decreased mechanical loading results in skeletal muscle atrophy. The transient receptor potential canonical type 1 (TRPC1) protein is implicated in this process. Investigation of the regulation of TRPC1 in vivo has rarely been reported. In the present study, we employ the mouse hindlimb unloading and reloading model to examine the involvement of TRPC1 in the regulation of muscle atrophy and regrowth, respectively.We establish the physiological relevance of the concept that manipulation of TRPC1 could interfere with muscle regrowth processes following an atrophy‐inducing event. Specifically, we show that suppressing TRPC1 expression during reloading impairs the recovery of the muscle mass and slow myosin heavy chain profile. Calcineurin appears to be part of the signalling pathway involved in the regulation of TRPC1 expression during muscle regrowth.These results provide new insights concerning the function of TRPC1. Interventions targeting TRPC1 or its downstream or upstream pathways could be useful for promoting muscle regeneration. Abstract Decreased mechanical loading, such as bed rest, results in skeletal muscle atrophy. The functional consequences of decreased mechanical loading include a loss of muscle mass and decreased muscle strength, particularly in anti‐gravity muscles. The purpose of this investigation was to clarify the regulatory role of the transient receptor potential canonical type 1 (TRPC1) protein during muscle atrophy and regrowth. Mice were subjected to 14 days of hindlimb unloading followed by 3, 7, 14 and 28 days of reloading. Weight‐bearing mice were used as controls. TRPC1 expression in the soleus muscle decreased significantly and persisted at 7 days of reloading. Small interfering RNA (siRNA)‐mediated downregulation of TRPC1 in weight‐bearing soleus muscles resulted in a reduced muscle mass and a reduced myofibre cross‐sectional area (CSA). Microinjecting siRNA into soleus muscles in vivo after 7 days of

  1. The involvement of transient receptor potential canonical type 1 in skeletal muscle regrowth after unloading-induced atrophy.

    PubMed

    Xia, Lu; Cheung, Kwok-Kuen; Yeung, Simon S; Yeung, Ella W

    2016-06-01

    Decreased mechanical loading results in skeletal muscle atrophy. The transient receptor potential canonical type 1 (TRPC1) protein is implicated in this process. Investigation of the regulation of TRPC1 in vivo has rarely been reported. In the present study, we employ the mouse hindlimb unloading and reloading model to examine the involvement of TRPC1 in the regulation of muscle atrophy and regrowth, respectively. We establish the physiological relevance of the concept that manipulation of TRPC1 could interfere with muscle regrowth processes following an atrophy-inducing event. Specifically, we show that suppressing TRPC1 expression during reloading impairs the recovery of the muscle mass and slow myosin heavy chain profile. Calcineurin appears to be part of the signalling pathway involved in the regulation of TRPC1 expression during muscle regrowth. These results provide new insights concerning the function of TRPC1. Interventions targeting TRPC1 or its downstream or upstream pathways could be useful for promoting muscle regeneration. Decreased mechanical loading, such as bed rest, results in skeletal muscle atrophy. The functional consequences of decreased mechanical loading include a loss of muscle mass and decreased muscle strength, particularly in anti-gravity muscles. The purpose of this investigation was to clarify the regulatory role of the transient receptor potential canonical type 1 (TRPC1) protein during muscle atrophy and regrowth. Mice were subjected to 14 days of hindlimb unloading followed by 3, 7, 14 and 28 days of reloading. Weight-bearing mice were used as controls. TRPC1 expression in the soleus muscle decreased significantly and persisted at 7 days of reloading. Small interfering RNA (siRNA)-mediated downregulation of TRPC1 in weight-bearing soleus muscles resulted in a reduced muscle mass and a reduced myofibre cross-sectional area (CSA). Microinjecting siRNA into soleus muscles in vivo after 7 days of reloading provided further evidence

  2. Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca(2+).

    PubMed

    Ojuka, Edward O; Jones, Terry E; Nolte, Lorraine A; Chen, May; Wamhoff, Brian R; Sturek, Michael; Holloszy, John O

    2002-05-01

    There is evidence suggesting that adaptive increases in GLUT4 and mitochondria in skeletal muscle occur in parallel. It has been reported that raising cytosolic Ca(2+) in myocytes induces increases in mitochondrial enzymes. In this study, we tested the hypothesis that an increase in cytosolic Ca(2+) induces an increase in GLUT4. We found that raising cytosolic Ca(2+) by exposing L6 myotubes to 5 mM caffeine for 3 h/day for 5 days induced increases in GLUT4 protein and in myocyte enhancer factor (MEF)2A and MEF2D, which are transcription factors involved in regulating GLUT4 expression. The caffeine-induced increases in GLUT4 and MEF2A and MEF2D were partially blocked by dantrolene, an inhibitor of sarcoplasmic reticulum Ca(2+) release, and completely blocked by KN93, an inhibitor of Ca(2+)-calmodulin-dependent protein kinase (CAMK). Caffeine also induced increases in MEF2A, MEF2D, and GLUT4 in rat epitrochlearis muscles incubated with caffeine in culture medium. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), which activates AMP-activated protein kinase (AMPK), also induced approximately twofold increases in GLUT4, MEF2A, and MEF2D in L6 myocytes. Our results provide evidence that increases in cytosolic Ca(2+) and activation of AMPK, both of which occur in exercising muscle, increase GLUT4 protein in myocytes and skeletal muscle. The data suggest that this effect of Ca(2+) is mediated by activation of CAMK and indicate that MEF2A and MEF2D are involved in this adaptive response.

  3. Levels of mercury in muscle and liver of star-spotted dogfish (Mustelus manazo) from the northern region of Japan: a comparison with spiny dogfish (Squalus acanthias).

    PubMed

    Endo, Tetsuya; Hisamichi, Yohsuke; Kimura, Osamu; Ogasawara, Hideki; Ohta, Chiho; Koga, Nobuyuki; Kato, Yoshihisa; Haraguchi, Koichi

    2013-04-01

    We analyzed mercury (Hg) concentrations in muscle and liver samples of star-spotted dogfish (Mustelus manazo) caught off the northern region of Japan and compared them with those of spiny dogfish (Squalus acanthias) caught in the same region. The average body length of male star-spotted dogfish specimens was significantly smaller than that of female specimens, reflecting the slower growth rate of male fish. Hg concentrations in liver and muscle increased with increases in body length and estimated age of both male and female star-spotted dogfish specimens. However, the relationships between Hg concentration in liver or muscle and body length or estimated age of male specimens differed markedly from those of female specimens, reflecting differences in growth rate and cessation of growth on reaching maturity. Marked increases in Hg concentration in liver of male and female star-spotted dogfish specimens were observed slightly later than increases in Hg concentration in muscle of those specimens due to growth cessation. These marked increases in Hg in liver may reflect increases in Hg due to the formation of mercury selenide. Similar results were previously reported in spiny dogfish specimens, except spiny dogfish showed only trace levels of Hg in liver (Endo et al., Chemosphere 77:1333-1337, 2009). The greater lipid content in liver and the larger liver size in spiny dogfish may explain the much lower levels of Hg observed in liver of spiny dogfish compared with those in the star-spotted dogfish.

  4. Superficial and deep infiltrating congenital juvenile xanthogranuloma involving multiple skeletal muscles and associated with ulceration and generalized postinvolution atrophy.

    PubMed

    Moon, Hye-Rim; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan

    2015-01-01

    We present a 2-day-old boy with a deep-seated giant juvenile xanthogranuloma infiltrating the skeletal muscles on his right lower limb. Unlike typical juvenile xanthogranuloma, the lesion has shown only partial spontaneous regression with large atrophic scar. However, despite the involvement multiple muscle on the right thigh, the patient has no evidence of orthopaedic sequelae. © 2014 Wiley Periodicals, Inc.

  5. Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis

    PubMed Central

    Fernandez-Marcos, Pablo J.; Jeninga, Ellen H.; Canto, Carles; Harach, Taoufiq; de Boer, Vincent C. J.; Andreux, Penelope; Moullan, Norman; Pirinen, Eija; Yamamoto, Hiroyasu; Houten, Sander M.; Schoonjans, Kristina; Auwerx, Johan

    2012-01-01

    Sirt3 is a mitochondrial sirtuin, predominantly expressed in highly metabolic tissues. Germline ablation of Sirt3 has major metabolic consequences, including increased susceptibility to metabolic damage and oxidative stress after high fat feeding. In order to determine the contribution of liver and skeletal muscle to these phenotypes, we generated muscle-specific Sirt3 (Sirt3skm−/−) and liver-specific Sirt3 (Sirt3hep−/−) knock-out mice. Despite a marked global hyperacetylation of mitochondrial proteins, Sirt3skm−/− and Sirt3hep−/− mice did not manifest any overt metabolic phenotype under either chow or high fat diet conditions. Similarly, there was no evidence for increased oxidative stress in muscle or liver when Sirt3 was ablated in a tissue-specific manner. These observations suggest that the mitochondrial hyperacetylation induced by Sirt3-deletion in a tissue specific manner is not necessarily linked to mitochondrial dysfunction and does not recapitulate the metabolic abnormalities observed in the germline Sirt3 knock-out mice. PMID:22645641

  6. Polyphenols decreased liver NADPH oxidase activity, increased muscle mitochondrial biogenesis and decreased gastrocnemius age-dependent autophagy in aged rats.

    PubMed

    Laurent, Caroline; Chabi, Beatrice; Fouret, Gilles; Py, Guillaume; Sairafi, Badie; Elong, Cecile; Gaillet, Sylvie; Cristol, Jean Paul; Coudray, Charles; Feillet-Coudray, Christine

    2012-09-01

    This study explored major systems of reactive oxygen species (ROS) production and their consequences on oxidative stress, mitochondriogenesis and muscle metabolism in aged rats, and evaluated the efficiency of 30-day oral supplementation with a moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In the liver of aged rats, NADPH oxidase activity was increased and mitochondrial respiratory chain complex activities were altered, while xanthine oxidase activity remained unchanged. In muscles, only mitochondrial activity was modified with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the aged rats without affecting global oxidative stress, suggesting that NADPH oxidase was probably not the dominant detrimental source of production of O(2)·(-) in the liver. Interestingly, RGPE supplementation increased mitochondrial biogenesis and improved antioxidant status in the gastrocnemius of aged rats, while it had no significant effect in soleus. RGPE supplementation also decreased age-dependent autophagy in gastrocnemius of aged rats. These results extended existing findings on the beneficial effects of RGPE on mitochondriogenesis and muscle metabolism in aged rats.

  7. Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis.

    PubMed

    Fernandez-Marcos, Pablo J; Jeninga, Ellen H; Canto, Carles; Harach, Taoufiq; de Boer, Vincent C J; Andreux, Penelope; Moullan, Norman; Pirinen, Eija; Yamamoto, Hiroyasu; Houten, Sander M; Schoonjans, Kristina; Auwerx, Johan

    2012-01-01

    Sirt3 is a mitochondrial sirtuin, predominantly expressed in highly metabolic tissues. Germline ablation of Sirt3 has major metabolic consequences, including increased susceptibility to metabolic damage and oxidative stress after high fat feeding. In order to determine the contribution of liver and skeletal muscle to these phenotypes, we generated muscle-specific Sirt3 (Sirt3(skm-/-)) and liver-specific Sirt3 (Sirt3(hep-/-)) knock-out mice. Despite a marked global hyperacetylation of mitochondrial proteins, Sirt3(skm-/-) and Sirt3(hep-/-) mice did not manifest any overt metabolic phenotype under either chow or high fat diet conditions. Similarly, there was no evidence for increased oxidative stress in muscle or liver when Sirt3 was ablated in a tissue-specific manner. These observations suggest that the mitochondrial hyperacetylation induced by Sirt3-deletion in a tissue specific manner is not necessarily linked to mitochondrial dysfunction and does not recapitulate the metabolic abnormalities observed in the germline Sirt3 knock-out mice.

  8. Myrtenal ameliorates hyperglycemia by enhancing GLUT2 through Akt in the skeletal muscle and liver of diabetic rats.

    PubMed

    Rathinam, Ayyasamy; Pari, Leelavinothan

    2016-08-25

    Insulin signaling pathway is an important role in glucose utilization in tissues. Our Previous study has established that myrtenal has antihyperglycemic effect against diabetic rats. The aim of this study was to explore the molecular mechanism of myrtenal in Streptozotocin-induced diabetic rats. Experimental diabetes was induced by single intraperitoneal injection of Streptozotocin (STZ) (40 mg/kg bw) in Wistar albino rats. Diabetic rats were administered myrtenal (80 mg/kg bw) for a period of 28 days. Diabetic rats showed an increased the levels of plasma glucose, decreased the levels of plasma insulin, down-regulation of insulin receptor substrate 2 (IRS2), Akt and glucose transporter 2 (GLUT2) in liver and insulin receptor substrate 2 (IRS2), Akt and glucose transporter 4 (GLUT4) protein expression in skeletal muscle. However, myrtenal treated diabetic rats revealed decreased the levels of plasma glucose, improved the plasma insulin levels, up-regulation of IRS2, Akt and GLUT2 in liver and IRS2, Akt and GLUT4 protein expression in skeletal muscle. The up-regulation of glucose transporters enhances the glucose uptake in liver and skeletal muscle. The histopathology and immunohistochemical analysis of the pancreas also corroborates with the above findings. Our findings suggest that myrtenal could be a potent phytochemical in the management of diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Heavy metals distribution in muscle, liver, kidney and gill of European catfish (Silurus glanis) from Italian Rivers.

    PubMed

    Squadrone, S; Prearo, M; Brizio, P; Gavinelli, S; Pellegrino, M; Scanzio, T; Guarise, S; Benedetto, A; Abete, M C

    2013-01-01

    The accumulation of heavy metals in freshwaters has direct consequences to man and ecosystem. Thus, in this study, the concentrations of mercury, cadmium, lead, arsenic and chromium in organs of the predator European catfish (Silurus glanis) were investigated. Samples were collected annually in five sites covering the area of the Po River (North Italy) between 2007 and 2009. Metals were differently distributed in the various organs, the highest concentrations of Hg were found in muscle and liver, Cd in kidney, Pb in gill and liver, as in muscle, and of Cr in gill and liver. Our survey found Hg exceeding the Maximum Levels (MLs) of 0.5 ppm in 18% of samples, while Pb and Cd were lower than the MLs set by European regulations in muscle tissues (1881/2006/EC and 629/2008/EC). Hg concentrations were significantly related to sampling stations studied, according to the presence of many industrial activities in the catchment area of Bormida and Tanaro Rivers. The finding that Hg did not fit food fish legislation limits indicated that S. glanis flesh might not be utilised for human consumption. A close monitoring of metals pollution is strongly recommended especially in piscivorous fish, cause their bioaccumulation capacity.

  10. Is hydrogen peroxide involved in the benzyl viologen-mediated in-vivo inactivation of rat liver glutamine synthetase?

    PubMed Central

    Muriana, F. J.; Ruiz-Gutierrez, V.; Relimpio, A. M.

    1993-01-01

    After benzyl viologen administration to rats, a decrease in the rat liver glutamine synthetase activity was observed. An increase in the rat liver catalase activity was found concomitantly. In combination with the catalase inhibitor aminotriazole, benzyl viologen again diminished, but markedly, the rat liver glutamine synthetase activity. Moreover, partially purified glutamine synthetase from rat liver underwent rapid inactivation upon aerobic incubation with NAD(P)H and benzyl viologen. This inactivation was prevented by catalase, which suggests that the NAD(P)H/BV2+/O2-dependent system has a role in H2O2 production. Our results suggest that H2O2 is involved in the benzyl viologen-mediated in-vivo inactivation of the rat liver glutamine synthetase. In contrast, benzyl viologen alone or in combination with aminotriazole produced a significant increase of brain glutamine synthetase. PMID:8098954

  11. Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle.

    PubMed

    Seo, Yun-Soo; Shon, Mi-Yae; Kong, Ryong; Kang, Ok-Hwa; Zhou, Tian; Kim, Do-Yeon; Kwon, Dong-Yeul

    2016-08-22

    Ginseng (Panax ginseng C. A. Meyer, Araliaceae) has been used as a traditional medicine for thousands of years for the treatment of a wide variety of diseases, including diabetes. Processed ginseng named Black ginseng exhibits more potent biological activities than white and red ginseng. The aim of this study was to investigate the effects of black ginseng extract (GBG05-FF) on hyperglycemia and glucose tolerance in streptozotocin (STZ)-induced diabetic mice. Black ginseng was produced by a repeated steaming and drying process, subsequent extraction with 70% ethanol, filtration, and lyophilization. The effect of GBG05-FF on glucose uptake and related protein expression and phosphorylation were determined in C2C12 cells. Furthermore, we evaluated the anti-diabetic effects of GBG05-FF in STZ-induced diabetic mice. GBG05-FF significantly (p<0.05) increased glucose uptake in C2C12 myotubes via AMPK, Sirt1 and PI3-K pathway. In addition, GBG05-FF improved the fasting blood glucose levels and glucose tolerance in STZ-induced diabetic mice. GBG05-FF decreased blood parameters such as glycated hemoglobin, triglyceride and total cholesterol. Quantitative RT-PCR assay revealed that in the STZ-induced diabetic mice treated with GBG05-FF, the expression of hepatic genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase)), glycogenolysis (liver glycogen phosphorylase (LGP)) and glycogenesis (glycogen synthase (GS)) was suppressed, while the expression of the genes involved in glucose uptake (glucose transporter (GLUT) 1, GLUT4) and β-oxidation (acyl-CoA oxidase (ACO), carnitine palmitoyl transferase 1a (CPT1a), mitochondrial medium chain acyl-CoA dehydrogenase (MCAD)) in muscle were increased. GBG05-FF delayed diabetes-associated muscle atrophy by activating mTOR. The major bioactive compounds including ginsenoside Rg1, Rg3(S), Rg3(R), Rg5, Rk1 and Rh4 were evaluated for glucose uptake effect in C2C12 myotubes; the data

  12. Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice.

    PubMed

    Egawa, Tatsuro; Tsuda, Satoshi; Goto, Ayumi; Ohno, Yoshitaka; Yokoyama, Shingo; Goto, Katsumasa; Hayashi, Tatsuya

    2017-01-01

    Diets enriched with advanced glycation end products (AGE) have recently been related to muscle dysfunction processes. However, it remains unclear whether long-term exposure to an AGE-enriched diet impacts physiological characteristics of skeletal muscles. Therefore, we explored the differences in skeletal muscle mass, contractile function and molecular responses between mice receiving a diet high in AGE (H-AGE) and low in AGE (L-AGE) for 16 weeks. There were no significant differences between L-AGE and H-AGE mice with regard to body weight, food intake or epididymal fat pad weight. However, extensor digitorum longus (EDL) and plantaris (PLA) muscle weights in H-AGE mice were lower compared with L-AGE mice. Higher levels of N ε -(carboxymethyl)-l-lysine, a marker for AGE, in EDL muscles of H-AGE mice were observed compared with L-AGE mice. H-AGE mice showed lower muscle strength and endurance in vivo and lower muscle force production of PLA muscle in vitro. mRNA expression levels of myogenic factors including myogenic factor 5 and myogenic differentiation in EDL muscle were lower in H-AGE mice compared with L-AGE mice. The phosphorylation status of 70-kDa ribosomal protein S6 kinase Thr389, an indicator of protein synthesis signalling, was lower in EDL muscle of H-AGE mice than that of L-AGE mice. These findings suggest that long-term exposure to an AGE-enriched diet impairs skeletal muscle growth and muscle contractile function, and that these muscle dysfunctions may be attributed to the inhibition of myogenic potential and protein synthesis.

  13. Metabolism of paraldehyde to acetaldehyde in liver microsomes. Evidence for the involvement of cytochrome P-450.

    PubMed

    Zaleska, M M; Gessner, P K

    1983-12-15

    A concentration-dependent acetaldehyde (AcH) generation was observed when paraldehyde was incubated with the mouse liver microsomal fraction. The process, which exhibited a requirement for oxygen and NADPH and was inhibited by carbon monoxide, was found to have a Km of 17.9 mM with respect to paraldehyde and a Vmax of 40.1 nmoles/mg protein/min with respect to AcH formation. NADH was much less effective as an electron donor than NADPH, though a more than additive increase in AcH generation was observed when both of these nucleotides were added to the incubation. The rate of microsomal AcH generation from paraldehyde was increased 2.5-fold by pretreatment of the mice with phenobarbital but only 0.6-fold by pretreatment with 3-methylcholanthrene. Pretreatment with 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A) resulted in 54% inhibition of the reaction rate. Addition of metopirone to the incubation inhibited AcH generation in a concentration-related fashion, the inhibition being greatest, proportionately, in microsomes from phenobarbital-pretreated animals. The above results conclusively indicate the involvement of cytochrome P-540 mixed function oxidase in the formation of AcH from paraldehyde by mouse liver microsomes. It is also postulated that this process may be accomplished in the reaction analogous to O-dealkylation.

  14. Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle

    PubMed Central

    Mackey, Abigail L.; Brandstetter, Simon; Schjerling, Peter; Bojsen-Moller, Jens; Qvortrup, Klaus; Pedersen, Mette M.; Doessing, Simon; Kjaer, Michael; Magnusson, S. Peter; Langberg, Henning

    2011-01-01

    The purpose of this study was to test the hypothesis that remodeling of skeletal muscle extracellular matrix (ECM) is involved in protecting human muscle against injury. Biopsies were obtained from medial gastrocnemius muscles after a single bout of electrical stimulation (B) or a repeated bout (RB) 30 d later, or 30 d after a single stimulation bout (RBc). A muscle biopsy was collected from the control leg for comparison with the stimulated leg. Satellite cell content, tenascin C, and muscle regeneration were assessed by immunohistochemistry; real-time PCR was used to measure mRNA levels of collagens, laminins, heat-shock proteins (HSPs), inflammation, and related growth factors. The large responses of HSPs, CCL2, and tenascin C detected 48 h after a single bout were attenuated in the RB trial, indicative of protection against injury. Satellite cell content and 12 target genes, including IGF-1, were elevated 30 d after a single bout. Among those displaying the greatest difference vs. control muscle, ECM laminin-β1 and collagen types I and III were elevated ∼6- to 9-fold (P<0.001). The findings indicate that the sequenced events of load-induced early deadhesion and later strengthening of skeletal muscle ECM play a role in protecting human muscle against future injury.—Mackey, A. L., Brandstetter, S., Schjerling, P., Bojsen-Moller, J., Qvortrup, K., Pedersen, M. M., Doessing, S. Kjaer, M., Magnusson, S. P., Langberg, H. Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle. PMID:21368102

  15. A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome

    PubMed Central

    2013-01-01

    Background The complexity of the skeletal muscle and the identification of numerous human disease-causing mutations in its constitutive proteins make it an interesting tissue for proteomic studies aimed at understanding functional relationships of interacting proteins in both health and diseases. Method We undertook a large-scale study using two-hybrid screens and a human skeletal-muscle cDNA library to establish a proteome-scale map of protein-protein interactions centered on proteins involved in limb-girdle muscular dystrophies (LGMD). LGMD is a group of more than 20 different neuromuscular disorders that principally affect the proximal pelvic and shoulder girdle muscles. Results and conclusion The interaction network we unraveled incorporates 1018 proteins connected by 1492 direct binary interactions and includes 1420 novel protein-protein interactions. Computational, experimental and literature-based analyses were performed to assess the overall quality of this network. Interestingly, LGMD proteins were shown to be highly interconnected, in particular indirectly through sarcomeric proteins. In-depth mining of the LGMD-centered interactome identified new candidate genes for orphan LGMDs and other neuromuscular disorders. The data also suggest the existence of functional links between LGMD2B/dysferlin and gene regulation, between LGMD2C/γ-sarcoglycan and energy control and between LGMD2G/telethonin and maintenance of genome integrity. This dataset represents a valuable resource for future functional investigations. PMID:23414517

  16. Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone.

    PubMed

    Parr, Maria Kristina; Zhao, Piwen; Haupt, Oliver; Ngueu, Sandrine Tchoukouegno; Hengevoss, Jonas; Fritzemeier, Karl Heinrich; Piechotta, Marion; Schlörer, Nils; Muhn, Peter; Zheng, Wen-Ya; Xie, Ming-Yong; Diel, Patrick

    2014-09-01

    The phytoectysteroid ecdysterone (Ecdy) was reported to stimulate protein synthesis and enhance physical performance. The aim of this study was to investigate underlying molecular mechanisms particularly the role of ER beta (ERβ). In male rats, Ecdy treatment increased muscle fiber size, serum IGF-1 increased, and corticosteron and 17β-estradiol (E2) decreased. In differentiated C2C12 myoblastoma cells, treatment with Ecdy, dihydrotestosterone, IGF-1 but also E2 results in hypertrophy. Hypertrophy induced by E2 and Ecdy could be antagonized with an antiestrogen but not by an antiandrogen. In HEK293 cells transfected with ER alpha (ERα) or ERβ, Ecdy treatment transactivated a reporter gene. To elucidate the role of ERβ in Ecdy-mediated muscle hypertrophy, C2C12 myotubes were treated with ERα (ALPHA) and ERβ (BETA) selective ligands. Ecdy and BETA treatment but not ALPHA induced hypertrophy. The effect of Ecdy, E2, and BETA could be antagonized by an ERβ-selective antagonist (ANTIBETA). In summary, our results indicate that ERβ is involved in the mediation of the anabolic activity of the Ecdy. These findings provide new therapeutic perspectives for the treatment of muscle injuries, sarcopenia, and cachectic disease, but also imply that such a substance could be abused for doping purposes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Exercise-Induced Alterations in Skeletal Muscle, Heart, Liver, and Serum Metabolome Identified by Non-Targeted Metabolomics Analysis.

    PubMed

    Starnes, Joseph W; Parry, Traci L; O'Neal, Sara K; Bain, James R; Muehlbauer, Michael J; Honcoop, Aubree; Ilaiwy, Amro; Christopher, Peter M; Patterson, Cam; Willis, Monte S

    2017-08-08

    The metabolic and physiologic responses to exercise are increasingly interesting, given that regular physical activity enhances antioxidant capacity, improves cardiac function, and protects against type 2 diabetes. The metabolic interactions between tissues and the heart illustrate a critical cross-talk we know little about. To better understand the metabolic changes induced by exercise, we investigated skeletal muscle (plantaris, soleus), liver, serum, and heart from exercise trained (or sedentary control) animals in an established rat model of exercise-induced aerobic training via non-targeted GC-MS metabolomics. Exercise-induced alterations in metabolites varied across tissues, with the soleus and serum affected the least. The alterations in the plantaris muscle and liver were most alike, with two metabolites increased in each (citric acid/isocitric acid and linoleic acid). Exercise training additionally altered nine other metabolites in the plantaris (C13 hydrocarbon, inosine/adenosine, fructose-6-phosphate, glucose-6-phosphate, 2-aminoadipic acid, heptadecanoic acid, stearic acid, alpha-tocopherol, and oleic acid). In the serum, we identified significantly decreased alpha-tocopherol levels, paralleling the increases identified in plantaris muscle. Eleven unique metabolites were increased in the heart, which were not affected in the other compartments (malic acid, serine, aspartic acid, myoinositol, glutamine, gluconic acid-6-phosphate, glutamic acid, pyrophosphate, campesterol, phosphoric acid, creatinine). These findings complement prior studies using targeted metabolomics approaches to determine the metabolic changes in exercise-trained human skeletal muscle. Specifically, exercise trained vastus lateralus biopsies had significantly increased linoleic acid, oleic acid, and stearic acid compared to the inactive groups, which were significantly increased in plantaris muscle in the present study. While increases in alpha-tocopherol have not been identified in

  18. Differential Fmo3 Gene Expression in Various Liver Injury Models Involving Hepatic Oxidative Stress in Mice

    PubMed Central

    Rudraiah, Swetha; Moscovitz, Jamie E.; Donepudi, Ajay C.; Campion, Sarah N.; Slitt, Angela L.; Aleksunes, Lauren M.; Manautou, José E.

    2015-01-01

    treatment in mice markedly increasedFmo3 gene expression. While BDL increased Fmo3 mRNA expression, protein level did not change. The discrepancy with Fmo3 induction in cholestatic models, ANIT and BDL, is not entirely clear. Results from Nrf2 KO mice with APAP suggest that the transcriptional regulation of Fmo3 during liver injury may not involve Nrf2. PMID:25193093

  19. Involvement of Oxidative Stress and Inflammation in Liver Injury Caused by Perfluorooctanoic Acid Exposure in Mice

    PubMed Central

    Yang, Bei; Zou, Weiying; Hu, Zhenzhen; Liu, Fangming; Zhou, Ling; Yang, Shulong; Kuang, Haibin; Wu, Lei; Wei, Jie; Wang, Jinglei; Zou, Ting; Zhang, Dalei

    2014-01-01

    Perfluorooctanoic acid (PFOA) is widely present in the environment and has been reported to induce hepatic toxicity in animals and humans. In this study, mice were orally administered different concentrations of PFOA (2.5, 5, or 10 mg/kg/day). Histological examination showed that the exposure to PFOA for 14 consecutive days led to serious hepatocellular injury and obvious inflammatory cell infiltration. In addition, malondialdehyde formation and hydrogen peroxide generation, indicators of oxidative stress, were significantly induced by PFOA treatment in the liver of mice. Furthermore, hepatic levels of interleukin-6, cyclooxygenase-2, and C-reactive protein, markers of inflammatory response, were markedly increased by exposure to PFOA in mice. These results demonstrated that PFOA-induced hepatic toxicity may be involved in oxidative stress and inflammatory response in mice. PMID:24724082

  20. Renal involvement in a syndrome of vasculitis complicating HBsAg negative cirrhosis of the liver.

    PubMed

    Montoliu, J; Darnell, A; Grau, J M; Torras, A; Revert, L

    1985-01-01

    Six HBsAg negative patients with cirrhosis of the liver (CL) presented with recurrent bouts of palpable purpura in the legs due to small vessel leucocytoclastic vasculitis. In addition, all patients had renal failure, proteinuria and microhaematuria. Renal biopsy disclosed either diffuse proliferative (3 cases) or focal necrotising glomerulonephritis with crescents (2 cases). One patient had IgM-IgG mixed cryoglobulinaemia (type II). Four patients died of complications of their CL. Hepatocellular carcinoma was found in 1 case. In the patient without renal biopsy renal function improved following steroids and cyclophosphamide. The pathogenesis of this syndrome of cutaneous vasculitis with severe glomerular involvement in CL is unknown but could be immune-complex mediated.

  1. Effect of lifelong football training on the expression of muscle molecular markers involved in healthy longevity.

    PubMed

    Mancini, A; Vitucci, D; Labruna, G; Imperlini, E; Randers, M B; Schmidt, J F; Hagman, M; Andersen, T R; Russo, R; Orrù, S; Krustrup, P; Salvatore, F; Buono, P

    2017-04-01

    We investigated whether lifelong football training affects the expression of healthy longevity-related muscle molecular markers. Biopsies were collected from the vastus lateralis muscle of 10 lifelong football-trained men (68.2 ± 3.0 years) and of 10 active untrained healthy men (66.7 ± 1.3 years). Gene and protein expression was measured by RTqPCR on RNA and by western blotting on protein extracts from muscle biopsies, respectively. The expression of AMPKα1/α2, NAMPT, TFAM and PGC1α, which are markers of oxidative metabolism, and MyHC β isoform expression was higher in the muscle of football-trained men vs untrained men. Also citrate synthase activity was higher in trained than in untrained men (109.3 ± 9.2 vs 75.1 ± 9.2 mU/mg). These findings were associated with a healthier body composition in trained than in untrained men [body weight: 78.2 ± 6.5 vs 91.2 ± 11.2 kg; body mass index BMI: 24.4 ± 1.6 vs 28.8 ± 4.0 kg m(-2); fat%: 22.6 ± 8.0 vs 31.4 ± 5.0%)] and with a higher maximal oxygen uptake (VO2max: 34.7 ± 3.8 vs 27.3 ± 4.0 ml/min/kg). Also the expression of proteins involved in DNA repair and in senescence suppression (Erk1/2, Akt and FoxM1) was higher in trained than in untrained men. At BMI- and age-adjusted multiple linear regression analysis, fat percentage was independently associated with Akt protein expression, and VO2max was independently associated with TFAM mRNA and with Erk1/2 protein expression. Lifelong football training increases the expression of key markers involved in muscle oxidative metabolism, and in the DNA repair and senescence suppression pathways, thus providing the molecular basis for healthy longevity.

  2. Muscle synergies involved in shifting the center of pressure while making a first step.

    PubMed

    Wang, Yun; Zatsiorsky, Vladimir M; Latash, Mark L

    2005-11-01

    We used the framework of the uncontrolled manifold (UCM) hypothesis to analyze multi-muscle synergies involved in making a step by a standing person. We hypothesized that leg and trunk muscles are organized into stable groups (muscle modes, M-modes) related to shifts of the center of pressure (COP) in the anterior-posterior and medio-lateral directions. Another hypothesis was that the magnitudes of the modes co-vary across repetitive trials to stabilize a certain magnitude of the COP shift in both directions. M-modes were defined using principal component analysis applied to indices of changes in the electromyographic (EMG) activity prior to releasing variable loads that were held by the subject using a pulley system. For the task of releasing the load behind the body three M-modes associated with a backward COP shift were defined. Four M-modes were defined for the task of releasing the load at the body side associated with a lateral COP shift. Multiple regression analysis was used to relate changes in the M-mode magnitudes to COP shifts. EMG changes prior to making a step were quantified over five 100 ms time windows before the lift-off of the stepping leg. Two components of the variance in the M-mode space computed across repetitions of a stepping task were quantified-a component that did not affect the average COP shift in a particular direction (variance within the UCM, V (UCM)), and a component that affected the COP shift (variance orthogonal to the UCM, V (ORT)). V (UCM) was significantly higher than V (ORT) for both directions of the COP shifts. This relation was observed for the M-modes in the stepping leg as well as in the support leg. The stepping leg showed a different time evolution of the ratio V (UCM)/V (ORT) such that the difference between the two variance components disappeared closer to the time of the lift-off. The findings corroborate both main hypotheses. The study supports a view that control of whole-body actions involves grouping the muscles

  3. Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle.

    PubMed

    Mackey, Abigail L; Brandstetter, Simon; Schjerling, Peter; Bojsen-Moller, Jens; Qvortrup, Klaus; Pedersen, Mette M; Doessing, Simon; Kjaer, Michael; Magnusson, S Peter; Langberg, Henning

    2011-06-01

    The purpose of this study was to test the hypothesis that remodeling of skeletal muscle extracellular matrix (ECM) is involved in protecting human muscle against injury. Biopsies were obtained from medial gastrocnemius muscles after a single bout of electrical stimulation (B) or a repeated bout (RB) 30 d later, or 30 d after a single stimulation bout (RBc). A muscle biopsy was collected from the control leg for comparison with the stimulated leg. Satellite cell content, tenascin C, and muscle regeneration were assessed by immunohistochemistry; real-time PCR was used to measure mRNA levels of collagens, laminins, heat-shock proteins (HSPs), inflammation, and related growth factors. The large responses of HSPs, CCL2, and tenascin C detected 48 h after a single bout were attenuated in the RB trial, indicative of protection against injury. Satellite cell content and 12 target genes, including IGF-1, were elevated 30 d after a single bout. Among those displaying the greatest difference vs. control muscle, ECM laminin-β1 and collagen types I and III were elevated ∼6- to 9-fold (P<0.001). The findings indicate that the sequenced events of load-induced early deadhesion and later strengthening of skeletal muscle ECM play a role in protecting human muscle against future injury.

  4. Involvement and mechanism of DGAT2 upregulation in the pathogenesis of alcoholic fatty liver disease

    PubMed Central

    Wang, Zhigang; Yao, Tong; Song, Zhenyuan

    2010-01-01

    The mechanisms involved in the development of alcoholic liver disease (ALD) are not well established. We investigated the involvement of acyl-CoA: diacylglycerol acyltransferase 2 (DGAT2) upregulation in mediating hepatic fat accumulation induced by chronic alcohol consumption. Chronic alcohol feeding caused fatty liver and increased hepatic DGAT2 gene and protein expression, concomitant with a significant suppression of hepatic MAPK/ERK kinase/extracellular regulated kinase 1/2 (MEK/ERK1/2) activation. In vitro studies demonstrated that specific inhibitors of the MEK/ERK1/2 pathway increased DGAT2 gene expression and triglyceride (TG) contents in HepG2 cells, whereas epidermal growth factor, a strong ERK1/2 activator, had the opposite effect. Moreover, chronic alcohol feeding decreased hepatic S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio, an indicator of disrupted transmethylation reactions. Mechanistic investigations revealed that N-acetyl-S-farnesyl-l-cysteine, a potent inhibitor of isoprenylcysteine carboxyl methyltransferase, suppressed ERK1/2 activation, followed by an enhanced DGAT2 expression and an elevated TG content in HepG2 cells. Lastly, we demonstrated that the beneficial effects of betaine supplementation in ALD were associated with improved SAM/SAH ratio, alleviated ERK1/2 inhibition, and attenuated DGAT2 upregulation. In conclusion, our data suggest that upregulation of DGAT2 plays an important role in the pathogenesis of ALD, and that abnormal methionine metabolism contributes, at least partially, to DGAT2 upregulation via suppression of MEK/ERK1/2 activation. PMID:20739640

  5. Involvement and mechanism of DGAT2 upregulation in the pathogenesis of alcoholic fatty liver disease.

    PubMed

    Wang, Zhigang; Yao, Tong; Song, Zhenyuan

    2010-11-01

    The mechanisms involved in the development of alcoholic liver disease (ALD) are not well established. We investigated the involvement of acyl-CoA: diacylglycerol acyltransferase 2 (DGAT2) upregulation in mediating hepatic fat accumulation induced by chronic alcohol consumption. Chronic alcohol feeding caused fatty liver and increased hepatic DGAT2 gene and protein expression, concomitant with a significant suppression of hepatic MAPK/ERK kinase/extracellular regulated kinase 1/2 (MEK/ERK1/2) activation. In vitro studies demonstrated that specific inhibitors of the MEK/ERK1/2 pathway increased DGAT2 gene expression and triglyceride (TG) contents in HepG2 cells, whereas epidermal growth factor, a strong ERK1/2 activator, had the opposite effect. Moreover, chronic alcohol feeding decreased hepatic S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio, an indicator of disrupted transmethylation reactions. Mechanistic investigations revealed that N-acetyl-S-farnesyl-L-cysteine, a potent inhibitor of isoprenylcysteine carboxyl methyltransferase, suppressed ERK1/2 activation, followed by an enhanced DGAT2 expression and an elevated TG content in HepG2 cells. Lastly, we demonstrated that the beneficial effects of betaine supplementation in ALD were associated with improved SAM/SAH ratio, alleviated ERK1/2 inhibition, and attenuated DGAT2 upregulation. In conclusion, our data suggest that upregulation of DGAT2 plays an important role in the pathogenesis of ALD, and that abnormal methionine metabolism contributes, at least partially, to DGAT2 upregulation via suppression of MEK/ERK1/2 activation.

  6. Effects of Petrol Exposure on Glucose, Liver and Muscle glycogen levels in the Common African toad Bufo regularis.

    PubMed

    Isehunwa, G O; Yusuf, I O; Alada, A Ar

    2017-03-06

    This study investigated the effects of exposure to petrol on blood glucose, liver and muscle glycogen levels in the common African toad Bufo regularis. A total of 126 adult toads of either sex weighing between 70-100g were used for this study. The experiment was divided into three phases. The phase 1 experiment the acute toxicity test consisted of animals divided into six groups of 10 toads per group and were exposed to water (H2O), H2O + Tween 80, 2ml/l, 3ml/l, 5ml/l, and 10ml/l of petrol respectively for 96 hours using the static renewal bioassay system. In the Phase 2 experiment, the animals were exposed to H2O, H2O + Tween 80, 0.14ml/l, 0.3ml/l, 0.6ml/l, and 1.13ml/l of petrol respectively for 3 days; while in phase 3 experiment they were exposed to petrol solutions for 14 days. After the various exposures, the blood glucose, liver and muscle glycogen contents were determined using standard methods. The results of the study showed that the median lethal concentration of petrol (96 hours LC50) was 4.5ml/l and sub-lethal concentration of petrol caused mortality of animals. Exposure to petrol solutions for 3 days had no significant effect on blood glucose level of the animals but caused significant decrease in the liver and muscle glycogen levels at high concentrations. In the animals exposed to petrol solutions for 14 days, there was a significant increase in glucose levels and significant reduction in liver and muscle glycogen levels at high concentrations when compared with the control. The results show that sub-lethal concentrations of petrol can cause mortality of animals, hyperglycemia and reduction in liver and muscle glycogen levels. The effects of petrol exposure on carbohydrate metabolism depend on the concentration and duration of exposure.

  7. Hyperhomocysteinemia associated skeletal muscle weakness involves mitochondrial dysfunction and epigenetic modifications.

    PubMed

    Veeranki, Sudhakar; Winchester, Lee J; Tyagi, Suresh C

    2015-05-01

    HHcy has been implicated in elderly frailty, but the underlying mechanisms are poorly understood. Using C57 and CBS+/- mice and C2C12 cell line, we investigated mechanisms behind HHcy induced skeletal muscle weakness and fatigability. Possible alterations in metabolic capacity (levels of LDH, CS, MM-CK and COX-IV), in structural proteins (levels of dystrophin) and in mitochondrial function (ATP production) were examined. An exercise regimen was employed to reverse HHcy induced changes. CBS+/- mice exhibited more fatigability, and generated less contraction force. No significant changes in muscle morphology were observed. However, there is a corresponding reduction in large muscle fiber number in CBS+/- mice. Excess fatigability was not due to changes in key enzymes involved in metabolism, but was due to reduced ATP levels. A marginal reduction in dystrophin levels along with a decrease in mitochondrial transcription factor A (mtTFA) were observed. There was also an increase in the mir-31, and mir-494 quantities that were implicated in dystrophin and mtTFA regulation respectively. The molecular changes elevated during HHcy, with the exception of dystrophin levels, were reversed after exercise. In addition, the amount of NRF-1, one of the transcriptional regulators of mtTFA, was significantly decreased. Furthermore, there was enhancement in mir-494 levels and a concomitant decline in mtTFA protein quantity in homocysteine treated cells. These changes in C2C12 cells were also accompanied by an increase in DNMT3a and DNMT3b proteins and global DNA methylation levels. Together, these results suggest that HHcy plays a causal role in enhanced fatigability through mitochondrial dysfunction which involves epigenetic changes.

  8. Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin-induced diabetic rats.

    PubMed

    Wang, Dongwen; Yuan, Xiaobin; Hu, Caoyang; Zhang, Bin; Gao, Hongfei; Wang, Dong; Chi, Junjie; Jing, Qiang; Wu, Shulin; Wu, Chin-Lee

    2017-01-01

    Endoplasmic reticulum stress (ERS) has been proven to be associated with apoptosis and plays a critical role in the development of many diabetic complications. In the pathogenesis of diabetic cystopathy (DCP), the role of ERS is still unclear. Our study is aimed at the investigation of the involvement of ERS-associated detrusor muscle apoptosis in streptozocin (STZ)-induced diabetic rats. At different timepoints (4, 8, 12, and 16 weeks after induction of type 1 diabetic rat models), hematoxylin & eosin (H&E) staining was performed to assess the histological changes of the diabetic detrusor; the sub-cellular ultrastructure, especially the zone of endoplasmic reticulum (ER), was observed by transmission electron microscopy (TEM), and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) staining was used to identify the enhanced apoptosis. Moreover, the expression of three hallmarks of ERS-associated apoptosis, including glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and caspase12, was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Light microscopic impairments of histology, including progressive loosely packed muscle bundles and increased fibrous tissue, can be seen; the ultrastructural changes featuring the swollen and fused cisternaes in ER zone and deformed nucleus were also observed in the detrusor smooth muscle (DSM). Increased apoptosis and elevated expression of GRP78, CHOP, and caspase12 at both protein and mRNA levels in a time-dependent fashion were detected. The occurrence of ERS-associated apoptosis may be involved in the development of DCP and may contribute to the diabetic detrusor impairment. Neurourol. Urodynam. 36:65-72, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  9. Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride-induced liver cirrhosis.

    PubMed

    Giusto, Michela; Barberi, Laura; Di Sario, Francesca; Rizzuto, Emanuele; Nicoletti, Carmine; Ascenzi, Francesca; Renzi, Anastasia; Caporaso, Nicola; D'Argenio, Giuseppe; Gaudio, Eugenio; Musarò, Antonio; Merli, Manuela

    2017-04-01

    Skeletal muscle myopathy is universal in cirrhotic patients, however, little is known about the main mechanisms involved. The study aims to investigate skeletal muscle morphological, histological, and functional modifications in experimental models of cirrhosis and the principal molecular pathways responsible for skeletal muscle myopathy. Cirrhosis was induced by bile duct ligation (BDL) and carbon tetrachloride (CCl4) administration in mice. Control animals (CTR) underwent bile duct exposure or vehicle administration only. At sacrifice, peripheral muscles were dissected and weighed. Contractile properties of extensor digitorum longus (EDL) were studied in vitro. Muscle samples were used for histological and molecular analysis. Quadriceps muscle histology revealed a significant reduction in cross-sectional area of muscle and muscle fibers in cirrhotic mice with respect to CTR. Kinetic properties of EDL in both BDL and CCl4 were reduced with respect to CTR; BDL mice also showed a reduction in muscle force and a decrease in the resistance to fatigue. Increase in myostatin expression associated with a decrease in AKT-mTOR expressions was observed in BDL mice, together with an increase in LC3 protein levels. Upregulation of the proinflammatory citochines TNF-a and IL6 and an increased expression of NF-kB and MuRF-1 were observed in CCl4 mice. In conclusion, skeletal muscle myopenia was present in experimental models of BDL and CCl4-induced cirrhosis. Moreover, reduction in protein synthesis and activation of protein degradation were the main mechanisms responsible for myopenia in BDL mice, while activation of ubiquitin-pathway through inflammatory cytokines seems to be the main potential mechanism involved in CCl4 mice.

  10. The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

    SciTech Connect

    Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun; Zheng, Timothy S.; Burkly, Linda C.; Kumar, Ashok

    2014-04-18

    Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways.

  11. Cytophotometric analysis of reaction rates of succinate and lactate dehydrogenase activity in rat liver, heart muscle and tracheal epithelium.

    PubMed

    Van Noorden, C J; Vogels, I M

    1989-01-01

    Reaction rates of succinate and lactate dehydrogenase activity in cryostat sections of rat liver, tracheal epithelium and heart muscle were monitored by continuous measurement of formazan formation by cytophotometry at room temperature. Incubation media contained polyvinyl alcohol as tissue protectant and Tetranitro BT as final electron acceptor. Control media lacked either substrate or substrate and coenzyme. Controls were also performed by adding malonate (a competitive inhibitor of succinate dehydrogenase), pyruvate (a non-competitive inhibitor of lactate dehydrogenase), oxalate (a competitive inhibitor of lactate dehydrogenase) or N-ethylmaleimide (a blocker of SH groups). A specific malonate-sensitive linear test minus control response for succinate dehydrogenase activity was obtained in liver (1.6 mumol H2cm-3 min-1) and tracheal epithelium (0.8 mumol H2cm-3 min-1) but not in heart muscle. All variations in the incubation conditions tested did not result in a linear test minus control response in the latter tissue. Because the reaction was sensitive to malonate, it was concluded that the initial reaction rate was the specific rate of succinate dehydrogenase activity in heart muscle (9.1 mumol H2 cm-3 min-1). Test minus control reactions for lactate dehydrogenase activity were distinctly non-linear for all tissues tested. This appeared to be due to product inhibition by pyruvate generated during the reaction and therefore it was concluded that the appropriate control reaction was the test reaction in the presence of 20 mM pyruvate. The initial rate of the test minus this control was the true rate of lactate dehydrogenase activity. The lactate dehydrogenase activity thus found in liver parenchyma was 5.0 mumol of H2 generated per cm3 liver tissue per min.

  12. Short-term pyrrolidine dithiocarbamate administration attenuates cachexia-induced alterations to muscle and liver in ApcMin/+ mice

    PubMed Central

    VanderVeen, Brandon N.; Enos, Reilly T.; Murphy, E. Angela; Carson, James A.

    2016-01-01

    Cancer cachexia is a complex wasting condition characterized by chronic inflammation, disrupted energy metabolism, and severe muscle wasting. While evidence in pre-clinical cancer cachexia models have determined that different systemic inflammatory inhibitors can attenuate several characteristics of cachexia, there is a limited understanding of their effects after cachexia has developed, and whether short-term administration is sufficient to reverse cachexia-induced signaling in distinctive target tissues. Pyrrolidine dithiocarbamate (PDTC) is a thiol compound having anti-inflammatory and antioxidant properties which can inhibit STAT3 and nuclear factor κB (NF-κB) signaling in mice. This study examined the effect of short-term PDTC administration to ApcMin/+ mice on cachexia-induced disruption of skeletal muscle protein turnover and liver metabolic function. At 16 weeks of age ApcMin/+ mice initiating cachexia (7% BW loss) were administered PDTC (10mg/kg bw/d) for 2 weeks. Control ApcMin/+ mice continued to lose body weight during the treatment period, while mice receiving PDTC had no further body weight decrease. PDTC had no effect on either intestinal tumor burden or circulating IL-6. In muscle, PDTC rescued signaling disrupting protein turnover regulation. PDTC suppressed the cachexia induction of STAT3, increased mTORC1 signaling and protein synthesis, and suppressed the induction of Atrogin-1 protein expression. Related to cachectic liver metabolic function, PDTC treatment attenuated glycogen and lipid content depletion independent to the activation of STAT3 and mTORC1 signaling. Overall, these results demonstrate short-term PDTC treatment to cachectic mice attenuated cancer-induced disruptions to muscle and liver signaling, and these changes were independent to altered tumor burden and circulating IL-6. PMID:27449092

  13. Domestication causes large-scale effects on gene expression in rainbow trout: analysis of muscle, liver and brain transcriptomes.

    PubMed

    Tymchuk, Wendy; Sakhrani, Dionne; Devlin, Robert

    2009-01-01

    Domestication has produced faster-growing strains of animals for use in agriculture, but selection has been applied with little knowledge of the underlying genetic changes that arose throughout the process. Mammals and birds have been domesticated for thousands of years whereas fish have been domesticated only recently; therefore, wild progenitor strains remain for comparison. Rainbow trout (Oncorhynchus mykiss) have undergone intensive selection and domesticated strains grow more rapidly than extant wild strains. To assess physiological pathways altered by domestication, whole-genome mRNA expression was measured in brain, muscle and liver of size-matched domestic and wild trout using a 16K (cGRASP) salmonid microarray. A large number of genes differed between strains, ranging from 3% of genes in brain to 9% in muscle. Domestic fish had more down-regulated genes in the brain relative to wild fish, whereas more genes were up-regulated in domestic liver and muscle. Relative to wild fish, there was a down-regulation of cell division and an up-regulation of structural genes in the brain of domestic fish. In liver from domestic fish, there was an up-regulation of genes related to transport with a down-regulation of lipid binding. Analysis of the functional categories for muscle indicated that most pathways, including pathways related to metabolism and catabolism, were up-regulated in domestic fish. Comparison of these results to other genomic studies on transgenic, domestic and wild salmonids suggests that similar physiological pathways are altered systemically to support faster rates of growth, regardless of the underlying genetic alteration that has caused the altered growth.

  14. Causality of Drugs Involved in Acute Liver Failure Leading to Transplantation: Results from the Study of Acute Liver Transplant (SALT).

    PubMed

    Gulmez, Sinem Ezgi; Moore, Nicholas; Pageaux, Georges-Philippe; Lignot, Severine; Horsmans, Yves; Stricker, Bruno; Bernuau, Jacques; Bissoli, Franco; Thorburn, Douglas; Montastruc, Jean-Louis; Micon, Sophie; Hamoud, Fatima; Lassalle, Régis; Jové, Jérémy; Blin, Patrick; Larrey, Dominique

    2013-09-01

    Several methods have been proposed to assess causality in drug-induced liver injury but none have been tested in the specific context of acute liver failure leading to transplantation (ALFT). We took advantage of the Study of Acute Liver Transplant (SALT), a European case-population study of ALFT, to test different causality scales. Causality was assessed by experts in SALT, a 7-country case-population study from 2005 to 2007 of adult otherwise unexplained ALFT, for all drugs found within 30 days prior to the date of initial symptoms of liver disease (index date), using information content, causality scales, and data circuit determined from a pilot study, Salome. The consensus points from Salome were to provide full data on drugs including international non-proprietary name (INN) and doses except for non-steroidal anti-inflammatory drugs (NSAIDs) and to use the World Health Organization (WHO) causality scale. In SALT, among the 9,479 identified patients, 600 (6.3%) were cases of ALFT, of which 187 had been exposed to drugs within 30 days, without overdose. In 130 (69.5%) of these the causality score was possible, probable, or highly probable. In ALFT cases, once other clinical causes have been excluded and drug exposure established within 30 days, the main discriminant characteristic for causality will be previous knowledge of possible hepatotoxicity.

  15. Characterization of a multiprotein complex involved in excitation-transcription coupling of skeletal muscle.

    PubMed

    Arias-Calderón, Manuel; Almarza, Gonzalo; Díaz-Vegas, Alexis; Contreras-Ferrat, Ariel; Valladares, Denisse; Casas, Mariana; Toledo, Héctor; Jaimovich, Enrique; Buvinic, Sonja

    2016-01-01

    markers citrate synthase and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were significantly increased by Panx1 overexpression. Interleukin 6 expression evoked by 20-Hz electrical stimulation (270 pulses, 0.3 ms each) was also significantly upregulated in L6-Panx1 cells. We propose the existence of a relevant multiprotein complex that coordinates events involved in E-T coupling. Unveiling the molecular actors involved in the regulation of gene expression will contribute to the understanding and treatment of skeletal muscle disorders due to wrong-expressed proteins, as well as to improve skeletal muscle performance.

  16. Transcriptome analysis reveals long intergenic non-coding RNAs involved in skeletal muscle growth and development in pig.

    PubMed

    Zou, Cheng; Li, Jingxuan; Luo, Wenzhe; Li, Long; Hu, An; Fu, Yuhua; Hou, Ye; Li, Changchun

    2017-08-18

    Long intergenic non-coding RNAs (lincRNAs) play essential roles in numerous biological processes and are widely studied. The skeletal muscle is an important tissue that plays an essential role in individual movement ability. However, lincRNAs in pig skeletal muscles are largely undiscovered and their biological functions remain elusive. In this study, we assembled transcriptomes using RNA-seq data published in previous studies of our laboratory group and identified 323 lincRNAs in porcine leg muscle. We found that these lincRNAs have shorter transcript length, fewer exons and lower expression level than protein-coding genes. Gene ontology and pathway analyses indicated that many potential target genes (PTGs) of lincRNAs were involved in skeletal-muscle-related processes, such as muscle contraction and muscle system process. Combined our previous studies, we found a potential regulatory mechanism in which the promoter methylation of lincRNAs can negatively regulate lincRNA expression and then positively regulate PTG expression, which can finally result in abnormal phenotypes of cloned piglets through a certain unknown pathway. This work detailed a number of lincRNAs and their target genes involved in skeletal muscle growth and development and can facilitate future studies on their roles in skeletal muscle growth and development.

  17. Molecular events and signalling pathways involved in skeletal muscle disuse-induced atrophy and the impact of countermeasures.

    PubMed

    Chopard, Angèle; Hillock, Steven; Jasmin, Bernard J

    2009-09-01

    Disuse-induced skeletal muscle atrophy occurs following chronic periods of inactivity such as those involving prolonged bed rest, trauma and microgravity environments. Deconditioning of skeletal muscle is mainly characterized by a loss of muscle mass, decreased fibre cross-sectional area, reduced force, increased fatigability, increased insulin resistance and transitions in fibre types. A description of the role of specific transcriptional mechanisms contributing to muscle atrophy by altering gene expression during muscle disuse has recently emerged and focused primarily on short period of inactivity. A better understanding of the transduction pathways involved in activation of proteolytic and apoptotic pathways continues to represent a major objective, together with the study of potential cross-talks in these cellular events. In parallel, evaluation of the impact of countermeasures at the cellular and molecular levels in short- and long-term disuse experimentations or microgravity environments should undoubtedly and synergistically increase our basic knowledge in attempts to identify new physical, pharmacological and nutritional targets to counteract muscle atrophy. These investigations are important as skeletal muscle atrophy remains an important neuromuscular challenge with impact in clinical and social settings affecting a variety of conditions such as those seen in aging, cancer cachexia, muscle pathologies and long-term space exploration.

  18. Molecular events and signalling pathways involved in skeletal muscle disuse-induced atrophy and the impact of countermeasures

    PubMed Central

    Chopard, Angèle; Hillock, Steven; Jasmin, Bernard J

    2009-01-01

    Disuse-induced skeletal muscle atrophy occurs following chronic periods of inactivity such as those involving prolonged bed rest, trauma and microgravity environments. Deconditioning of skeletal muscle is mainly characterized by a loss of muscle mass, decreased fibre cross-sectional area, reduced force, increased fatigability, increased insulin resistance and transitions in fibre types. A description of the role of specific transcriptional mechanisms contributing to muscle atrophy by altering gene expression during muscle disuse has recently emerged and focused primarily on short period of inactivity. A better understanding of the transduction pathways involved in activation of proteolytic and apoptotic pathways continues to represent a major objective, together with the study of potential cross-talks in these cellular events. In parallel, evaluation of the impact of countermeasures at the cellular and molecular levels in short- and long-term disuse experimentations or microgravity environments should undoubtedly and synergistically increase our basic knowledge in attempts to identify new physical, pharmacological and nutritional targets to counteract muscle atrophy. These investigations are important as skeletal muscle atrophy remains an important neuromuscular challenge with impact in clinical and social settings affecting a variety of conditions such as those seen in aging, cancer cachexia, muscle pathologies and long-term space exploration. PMID:19656243

  19. Iron overload-induced rat liver injury: Involvement of protein tyrosine nitration and the effect of baicalin.

    PubMed

    Zhang, Yan; Huang, Yi; Deng, Xiaorong; Xu, Yan; Gao, Zhonghong; Li, Hailing

    2012-04-05

    Baicalin has been reported to protect against liver injury in iron-overload mice, however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In this study, we systematically studied the protective effect of baicalin on iron overload induced liver injury, as well as the underlying mechanism based on nitrative stress in rat model. We found that when iron overload rats (500mgiron/kg) were fed baicalin-containing diet (0.3% and 1% w/w) for 45days, baicalin dose dependently protected against iron overload induced liver injury, including alleviation of hepatic pathological damage, decrease of SOD activity, iron content, carbonyl content, and the thiobarbituric acid-reactive substances level in hepatic tissues. It also increased serum iron content, SH content and GPx activity, decreased serum ALT and AST activities. Immunohistochemistry and immunoprecipitation analysis revealed that baicalin could also inhibit iron overload induced protein tyrosine nitration in liver. Moreover, in iron overload rat liver, we found that baicalin decreased the iron overload increased level of glutathione-S-transferases (GSTs) expression, oxidation and nitration. These results suggest that not only oxidative stress, but also nitrative stress, is involved in iron overload induced liver injury, and the underlying mechanism might partially relate to the involvement of GSTs expression and post-translational modification. Baicalin can effectively prevent iron overload caused abnormality and can be a candidate medicine for iron overload diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. The Involving Roles of Intrahepatic and Extrahepatic Stem/Progenitor Cells (SPCs) to Liver Regeneration

    PubMed Central

    Liu, Wei-hui; Ren, Li-na; Wang, Tao; Navarro-Alvarez, Nalu; Tang, Li-jun

    2016-01-01

    Liver regeneration is usually attributed to mature hepatocytes, which possess a remarkable potential to proliferate under mild to moderate injury. However, when the liver is severely damaged or hepatocyte proliferation is greatly inhibited, liver stem/progenitor cells (LSPCs) will contribute to the liver regeneration process. LSPCs in the developing liver have been extensively characterized, however, their contributing role to liver regeneration has not been completely understood. In addition to the restoration of the liver parenchymal tissue by hepatocytes or/and LSPCs, or in some cases bone marrow (BM) derived cells, such as hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), the wound healing after injury in terms of angiopoiesis by liver sinusoidal endothelial cells (LSECs) or/and sinusoidal endothelial progenitor cells (SEPCs) is another important aspect taking place during regeneration. To conclude, liver regeneration can be mainly divided into three distinct restoring levels according to the cause and severity of injury: hepatocyte dominant regeneration, LSPCs mediated regeneration, extrahepatic stem cells participative regeneration. In this review, we focus on the recent findings of liver regeneration, especially on those related to stem/progenitor cells (SPCs)-mediated regeneration and their potential clinical applications and challenges. PMID:27489499

  1. Sorafenib: muscle wasting.

    PubMed

    2011-12-01

    Sorafenib inhibits multiple kinases involved in angiogenesis and tumour growth. It is used for second-line treatment of advanced kidney cancer and some forms of liver cancer. A placebo-controlled trial in 80 patients with metastatic kidney cancer showed a statistically significant increase in muscle loss during sorafenib therapy. Skeletal muscle mass fell by about 5% after 6 months of treatment and by 8% after one year. In practice, patients treated with sorafenib should be assessed for muscle wasting. The clinical consequences of muscle wasting--loss of autonomy and walking difficulties--should be considered when weighing the benefits and harms of sorafenib therapy.

  2. Microarray analysis of gene expression in liver, adipose tissue and skeletal muscle in response to chronic dietary administration of NDGA to high-fructose fed dyslipidemic rats.

    PubMed

    Zhang, Haiyan; Shen, Wen-Jun; Li, Yihang; Bittner, Alex; Bittner, Stefanie; Tabassum, Juveria; Cortez, Yuan F; Kraemer, Fredric B; Azhar, Salman

    2016-01-01

    Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote Bush, has been shown to have profound effects on the core components of metabolic syndrome, including lowering of blood glucose, free fatty acids and triglyceride levels, attenuating elevated blood pressure in several rodent models of dyslipidemia, and improving body weight, insulin resistance, diabetes and hypertension. In the present study, a high-fructose diet fed rat model of hypertriglyceridemia, dyslipidemia, insulin resistance and hepatic steatosis was employed to investigate the global transcriptional changes in the lipid metabolizing pathways in three insulin sensitive tissues: liver, skeletal muscle and adipose tissue in response to chronic dietary administration of NDGA. Sprague-Dawley male rats (SD) were fed a chow (control) diet, high-fructose diet (HFrD) or HFrD supplemented with NDGA (2.5 g/kg diet) for eight weeks. Dietary administration of NDGA decreased plasma levels of TG, glucose, and insulin, and attenuated hepatic TG accumulation. DNA microarray expression profiling indicated that dietary administration of NDGA upregulated the expression of certain genes involved in fatty acid oxidation and their transcription regulator, PPARα, decreased the expression of a number of lipogenic genes and relevant transcription factors, and differentially impacted the genes of fatty acid transporters, acetyl CoA synthetases, elongases, fatty acid desaturases and lipid clearance proteins in liver, skeletal muscle and adipose tissues. These findings suggest that NDGA ameliorates hypertriglyceridemia and steatosis primarily by inhibiting lipogenesis and enhancing fatty acid catabolism in three major insulin responsive tissues by altering the expression of key enzyme genes and transcription factors involved in de novo lipogenesis and fatty acid oxidation.

  3. The involvement of reactive oxygen species in hypoxic injury to rat liver.

    PubMed

    Younes, M; Strubelt, O

    1988-03-01

    Isolated perfused livers from fasted, but not from fed rats showed hepatotoxic responses when subjected to 30 min of hypoxia followed by 60 min of reoxygenation. Toxicity was evident by a release of glutamate-pyruvate-transaminase, lactate dehydrogenase and glutathione into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. This indicates, that the liver is resistant to hypoxic injury as long as glycogen is present to maintain anaerobic ATP-synthesis. This is substantiated by the fact that addition of fructose--but not glucose--to the medium resulted in a protection of the liver against hypoxic injury concomitant with its degradation to lactate + pyruvate. Superoxide dismutase, catalase, desferrioxamine and allopurinol prevented hypoxic liver injury suggesting a substantial role of reactive oxygen species formed via the xanthine oxidase reaction in mediating hypoxic liver injury.

  4. Development-related expression patterns of protein-coding and miRNA genes involved in porcine muscle growth.

    PubMed

    Wang, F J; Jin, L; Guo, Y Q; Liu, R; He, M N; Li, M Z; Li, X W

    2014-11-27

    Muscle growth and development is associated with remarkable changes in protein-coding and microRNA (miRNA) gene expression. To determine the expression patterns of genes and miRNAs related to muscle growth and development, we measured the expression levels of 25 protein-coding and 16 miRNA genes in skeletal and cardiac muscles throughout 5 developmental stages by quantitative reverse transcription-polymerase chain reaction. The Short Time-Series Expression Miner (STEM) software clustering results showed that growth-related genes were downregulated at all developmental stages in both the psoas major and longissimus dorsi muscles, indicating their involvement in early developmental stages. Furthermore, genes related to muscle atrophy, such as forkhead box 1 and muscle ring finger, showed unregulated expression with increasing age, suggesting a decrease in protein synthesis during the later stages of skeletal muscle development. We found that development of the cardiac muscle was a complex process in which growth-related genes were highly expressed during embryonic development, but they did not show uniform postnatal expression patterns. Moreover, the expression level of miR-499, which enhances the expression of the β-myosin heavy chain, was significantly different in the psoas major and longissimus dorsi muscles, suggesting the involvement of miR-499 in the determination of skeletal muscle fiber types. We also performed correlation analyses of messenger RNA and miRNA expression. We found negative relationships between miR-486 and forkhead box 1, and miR-133a and serum response factor at all developmental stages, suggesting that forkhead box 1 and serum response factor are potential targets of miR-486 and miR-133a, respectively.

  5. Cadmium and zinc in kidney, liver, muscle and mammary tissue from dairy cows in conventional and organic farming.

    PubMed

    Olsson, I M; Jonsson, S; Oskarsson, A

    2001-10-01

    Input of Cd to arable soils occurs mainly through atmospheric deposition and mineral fertilisers. Phosphate fertilisers are often contaminated with Cd. In organic farming the use of mineral fertilisers is restricted. The impact of conventional and organic farming on Cd and Zn levels in tissues from dairy cows was studied. Kidney, liver, muscle and mammary tissue samples were collected at slaughter from 67 cows, aged 30-95 months, in a project with conventional and organic production at the same farm. Samples were analysed by electrothermal atomic absorption spectrometry with a quality control programme. Significantly lower levels of Cd were found in cows from the organic system (n = 29) than from the conventional cows (n = 38) in kidney [330 +/- 100 (mean +/- s) micrograms kg-1 vs. 410 +/- 140], liver (33 +/- 15 vs. 44 +/- 19) and mammary tissue (0.38 +/- 0.14 vs. 0.59 +/- 0.37), while there were no differences in muscle (0.48 +/- 0.13 vs. 0.49 +/- 0.14). Organic cow kidneys had lower Zn levels than conventional cows (19 +/- 1.4 mg kg-1 vs. 20 +/- 2), whereas muscles had higher Zn levels than conventional cows (67 +/- 16 vs. 51 +/- 12). Cd and Zn in mammary tissue were positively related to age and milk production. There was a positive relationship between levels in kidney of Cd and metallothionein (MT) and a Cd/MT concentration ratio indicating protection from Cd-induced renal dysfunction. When older animals, that entered the project as milk-producing cows, were included the differences in kidney and liver Cd levels between the systems were no longer significant, while Cd in kidney became related to age- and production-related parameters. The change of significant relationships when older animals were included shows the importance of controlled conditions for environmental monitoring.

  6. Synthesis of Essential Amino Acids from Their α-Keto Analogues by Perfused Rat Liver and Muscle

    PubMed Central

    Walser, Mackenzie; Lund, Patricia; Ruderman, Neil B.; Coulter, A. W.

    1973-01-01

    Most essential amino acids can be replaced by their α-keto-analogues in the diet. These ketoacids have therefore been proposed as substitutes for dietary protein. In order to determine their fate in tissues of normal animals, isolated rat liver and hindquarter (muscle) preparations were perfused with keto-analogues of valine, leucine, isoleucine, methionine, or phenylalanine. When perfused at 1.5-2.0 mM, all five compounds were utilized rapidly by the liver of 48-h starved rats, at rates varying from 49 to 155 μmol/h per 200g rat. The corresponding amino acids appeared in the medium in significantly increased concentrations. Perfusion with phenylpyruvate also led to the appearance of tyrosine. Urea release was unaltered. Measurement of metabolite concentrations in freeze-clamped liver revealed two abnormalities, particularly at ketoacid concentrations of 5 mM or above: a large increase in α-ketoglutarate, and a moderate to marked decrease in tissue glutamine. This decrease was quantitatively sufficient to account for nitrogen appearing in newly synthesized amino acids. Isolated hindquarters of fed rats were perfused with the same ketoacids at concentrations of 1.3-8.0 mM. All were utilized at rates varying from 1.4 to 7.0 μmol/h per g muscle perfused. The corresponding amino acids were released at greatly increased rates. Alanine and glutamate levels fell in some perfusions, but the principal nitrogen donor in muscle was not identified; the content of glutamine in tissue, and its rate of release into the perfusate remained constant. PMID:4748513

  7. Impact of Skeletal Muscle Mass Index, Intramuscular Adipose Tissue Content, and Visceral to Subcutaneous Adipose Tissue Area Ratio on Early Mortality of Living Donor Liver Transplantation.

    PubMed

    Hamaguchi, Yuhei; Kaido, Toshimi; Okumura, Shinya; Kobayashi, Atsushi; Shirai, Hisaya; Yagi, Shintaro; Kamo, Naoko; Okajima, Hideaki; Uemoto, Shinji

    2017-03-01

    Skeletal muscle depletion has been shown to be an independent risk factor for poor survival in various diseases. However, in surgery, the significance of other body components including visceral and subcutaneous adipose tissue remains unclear. This retrospective study included 250 adult patients undergoing living donor liver transplantation (LDLT) between January 2008 and April 2015. Using preoperative plain computed tomography imaging at the third lumbar vertebra level, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by the skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral to subcutaneous adipose tissue area ratio (VSR), respectively. The cutoff values of these parameters were determined for men and women separately using the data of 657 healthy donors for LDLT between 2005 and 2016. Impact of these parameters on outcomes after LDLT was analyzed. VSR was significantly correlated with patient age (P = 0.041), neutrophil-lymphocyte ratio (P < 0.001), body mass index (P < 0.001), and SMI (P = 0.001). The overall survival probability was significantly lower in patients with low SMI (P < 0.001), high IMAC (P < 0.001), and high VSR (P < 0.001) than in each respective normal group. On multivariate analysis, low SMI (hazard ratio [HR], 2.367, P = 0.002), high IMAC (HR, 2.096, P = 0.004), and high VSR (HR, 2.213, P = 0.003) were identified as independent risk factors for death after LDLT. Preoperative visceral adiposity, as well as low muscularity, was closely involved with posttransplant mortality.

  8. Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers.

    PubMed Central

    Schmitt-Gräff, A.; Krüger, S.; Bochard, F.; Gabbiani, G.; Denk, H.

    1991-01-01

    It has been suggested that perisinusoidal liver cells (PSC) play a pivotal role in the pathogenesis of fibrocontractive changes. Using light and electron microscopic immunolocalization techniques, a series of 207 normal and pathologic human liver specimens were evaluated for the expression of alpha smooth muscle (SM) actin and desmin in this and other nonparenchymal cell types. In normal adult liver tissue, PSCs were practically devoid of desmin and exceptionally stained for alpha-SM actin, whereas this actin isoform frequently was encountered in PSCs from the embryonic to the adolescent period. A broad spectrum of pathologic conditions was accompanied by the presence of alpha-SM actin containing PSCs; these were detected preferentially in periportal or perivenular zones according to the predominant location of the underlying hepatocellular damage. The occurrence of this PSC phenotype generally was associated with fibrogenesis and was in some cases detected earlier than overt collagen accumulation. Fibrous bands subdividing liver tissue in cirrhosis and focal nodular hyperplasia, as well as desmoplastic reaction to malignant tumors, contained alpha-SM actin-rich cells admixed with variable proportions of cells coexpressing desmin. In end stages, this population was less numerous than in active fibrotic or cirrhotic processes. Using immunogold electron microscopy, alpha-SM actin was localized in microfilament bundles of typical PSCs. Our results are compatible with the assumption that the appearance of alpha-SM actin and desmin-expressing myofibroblasts results at least in part from a phenotypic modulation of PSCs. Images Figure 1 Figure 2 PMID:2024709

  9. Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain.

    PubMed

    Bao, Xiaohang; Cai, Yulong; Wang, Ying; Zhao, Jinghui; He, Xie; Yu, Dan; Huang, Jing; Jing, Sheng; Du, Zhiyong; Yang, Tiande; Warner, Margaret; Gustafsson, Jan-Ake; Fan, Xiaotang

    2017-03-01

    Increasing evidence indicates that the liver X receptor(LXR) β modulates inflammatory pain. However, the molecular mechanisms through which LXRβ modulates pain are unclear. Here, we found that LXRβ-null mice responded more strongly to acute noxious stimuli than wild-type (WT) littermates (in the hot plate and Hargreaves tests) and had augmented tonic inflammatory pain (in the formalin test). This increased reactivity to inflammatory pain was accompanied by enhanced formalin-evoked Fos and pERK staining of second-order nociceptive neurons. Immunohistochemistry showed that the expression of CGRP, SP, and IB4 was increased in the lamina I-II of the lumbar dorsal horns in formalin-injected LXRβ knockout (KO) mice compared with the WT controls. In addition, LXRβ deletion in the mice enhanced the formalin-induced inflammation with more activated microglia and astrocytes in the spinal cord. Furthermore, the levels of pro-inflammatory cytokines (IL-1β ,TNF-α) as well as NFκB in the formalin-injected paw were elevated by the loss of LXRβ. Taken together, these data indicate that LXRβ is involved in acute as well as inflammatory pain, and thus, it may be considered as a new target for the development of analgesics.

  10. Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis.

    PubMed

    Kitajima, Yoichiro; Takahashi, Hirokazu; Akiyama, Takumi; Murayama, Kenichiro; Iwane, Shinji; Kuwashiro, Takuya; Tanaka, Kenichi; Kawazoe, Seiji; Ono, Naofumi; Eguchi, Takahisa; Anzai, Keizo; Eguchi, Yuichiro

    2017-07-24

    Liver cirrhosis induces marked metabolic disorders, protein-energy malnutrition, and sarcopenia. The objective of the study reported here was to investigate the effects of dietary branched-chain amino acids (BCAAs) on systemic glucose metabolism, skeletal muscle, and prognosis of patients with liver cirrhosis. Japanese patients with liver cirrhosis (n = 21) were enrolled into a longitudinal study in which their diets were supplemented with BCAAs. We evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI) and intramuscular adipose tissue content (IMAC) using computed tomography. After 48 weeks of supplementation with BCAAs, there were no changes in glucose metabolism and skeletal muscle findings. In patients with ameliorated hypoalbuminemia, IMAC was significantly decreased and SAI was preserved concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels (P < 0.01 each). In patients without increased albumin levels, IMAC was significantly increased and the SAI was significantly decreased (P < 0.01 each). Liver-related event-free survival rates for 72 months were 63.6% in patients with decreased IMAC and 20.0% in patients with increased IMAC. Amelioration of hypoalbuminemia associated with BCAA supplementation correlated with decreased fat accumulation in skeletal muscle, maintenance of skeletal muscle mass, and improved glucose sensitivity, all factors which may contribute to improving the survival of patients with liver cirrhosis.

  11. Developmental Stage, Muscle and Genetic Type Modify Muscle Transcriptome in Pigs: Effects on Gene Expression and Regulatory Factors Involved in Growth and Metabolism

    PubMed Central

    Ayuso, Miriam; Fernández, Almudena; Núñez, Yolanda; Benítez, Rita; Isabel, Beatriz; Fernández, Ana I.; Rey, Ana I.; González-Bulnes, Antonio; Medrano, Juan F.; Cánovas, Ángela; López-Bote, Clemente J.

    2016-01-01

    Iberian pig production includes purebred (IB) and Duroc-crossbred (IBxDU) pigs, which show important differences in growth, fattening and tissue composition. This experiment was conducted to investigate the effects of genetic type and muscle (Longissimus dorsi (LD) vs Biceps femoris (BF)) on gene expression and transcriptional regulation at two developmental stages. Nine IB and 10 IBxDU piglets were slaughtered at birth, and seven IB and 10 IBxDU at four months of age (growing period). Carcass traits and LD intramuscular fat (IMF) content were measured. Muscle transcriptome was analyzed on LD samples with RNA-Seq technology. Carcasses were smaller in IB than in IBxDU neonates (p < 0.001), while growing IB pigs showed greater IMF content (p < 0.05). Gene expression was affected (p < 0.01 and Fold change > 1.5) by the developmental stage (5,812 genes), muscle type (135 genes), and genetic type (261 genes at birth and 113 at growth). Newborns transcriptome reflected a highly proliferative developmental stage, while older pigs showed upregulation of catabolic and muscle functioning processes. Regarding the genetic type effect, IBxDU newborns showed enrichment of gene pathways involved in muscle growth, in agreement with the higher prenatal growth observed in these pigs. However, IB growing pigs showed enrichment of pathways involved in protein deposition and cellular growth, supporting the compensatory gain experienced by IB pigs during this period. Moreover, newborn and growing IB pigs showed more active glucose and lipid metabolism than IBxDU pigs. Moreover, LD muscle seems to have more active muscular and cell growth, while BF points towards lipid metabolism and fat deposition. Several regulators controlling transcriptome changes in both genotypes were identified across muscles and ages (SIM1, PVALB, MEFs, TCF7L2 or FOXO1), being strong candidate genes to drive expression and thus, phenotypic differences between IB and IBxDU pigs. Many of the identified regulators

  12. Developmental Stage, Muscle and Genetic Type Modify Muscle Transcriptome in Pigs: Effects on Gene Expression and Regulatory Factors Involved in Growth and Metabolism.

    PubMed

    Ayuso, Miriam; Fernández, Almudena; Núñez, Yolanda; Benítez, Rita; Isabel, Beatriz; Fernández, Ana I; Rey, Ana I; González-Bulnes, Antonio; Medrano, Juan F; Cánovas, Ángela; López-Bote, Clemente J; Óvilo, Cristina

    2016-01-01

    Iberian pig production includes purebred (IB) and Duroc-crossbred (IBxDU) pigs, which show important differences in growth, fattening and tissue composition. This experiment was conducted to investigate the effects of genetic type and muscle (Longissimus dorsi (LD) vs Biceps femoris (BF)) on gene expression and transcriptional regulation at two developmental stages. Nine IB and 10 IBxDU piglets were slaughtered at birth, and seven IB and 10 IBxDU at four months of age (growing period). Carcass traits and LD intramuscular fat (IMF) content were measured. Muscle transcriptome was analyzed on LD samples with RNA-Seq technology. Carcasses were smaller in IB than in IBxDU neonates (p < 0.001), while growing IB pigs showed greater IMF content (p < 0.05). Gene expression was affected (p < 0.01 and Fold change > 1.5) by the developmental stage (5,812 genes), muscle type (135 genes), and genetic type (261 genes at birth and 113 at growth). Newborns transcriptome reflected a highly proliferative developmental stage, while older pigs showed upregulation of catabolic and muscle functioning processes. Regarding the genetic type effect, IBxDU newborns showed enrichment of gene pathways involved in muscle growth, in agreement with the higher prenatal growth observed in these pigs. However, IB growing pigs showed enrichment of pathways involved in protein deposition and cellular growth, supporting the compensatory gain experienced by IB pigs during this period. Moreover, newborn and growing IB pigs showed more active glucose and lipid metabolism than IBxDU pigs. Moreover, LD muscle seems to have more active muscular and cell growth, while BF points towards lipid metabolism and fat deposition. Several regulators controlling transcriptome changes in both genotypes were identified across muscles and ages (SIM1, PVALB, MEFs, TCF7L2 or FOXO1), being strong candidate genes to drive expression and thus, phenotypic differences between IB and IBxDU pigs. Many of the identified regulators

  13. Sublethal toxicity of commercial formulations of deltamethrin and permethrin on selected biochemical constituents and enzyme activities in liver and muscle tissues of Anabas testudineus.

    PubMed

    Sapana Devi, Maisnam; Gupta, Abhik

    2014-10-01

    The freshwater fish Anabas testudineus was exposed for 21 days to two commercial formulations of synthetic pyrethroids deltamethrin and permethrin at sublethal concentrations of 0.007 and 0.0007 mg L(-1), and 0.093 and 0.0093 mg L(-1), that represented 10% and 1%, respectively, of the 96 h LC50 of these two pesticides for this fish. The glycogen, protein and lactic acid contents, along with succinate dehydrogenase (SDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) enzyme activities in liver and muscle tissues of control and pesticide-exposed fish were estimated. When compared with those of control fish, significant depletion of glycogen content was observed in liver, and that of protein in muscle tissue of fish treated with both the pesticides at their higher as well as lower concentrations. Lactic acid reduction was significant only in fish muscle treated with deltamethrin. SDH level was reduced significantly in both liver and muscle tissues except in fish exposed to 0.0093 mg L(-1) permethrin. AST level was reduced significantly in liver and muscle tissues and ALT in muscle tissue of deltamethrin treated fish only. It is concluded that deltamethrin, a type-II pyrethroid, is more toxic to fish than the type-I pyrethroid permethrin and is capable of rendering toxicity at a dose as low as 1% of its LC50 value. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    SciTech Connect

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

    2015-05-15

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

  15. Pterostilbene improves glycaemic control in rats fed an obesogenic diet: Involvement of skeletal muscle and liver

    USDA-ARS?s Scientific Manuscript database

    This study aimed to determine whether pterostilbene improved glycaemic control in rats showing insulin resistance induced by an obesogenic diet. Rats were divided into 3 groups: control group and two groups treated with either 15 mg/kg/d (PT15) or 30 mg/kg/d of pterostilbene (PT30). HOMA-IR was decr...

  16. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability.

    PubMed

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-08-05

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability.

  17. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    PubMed Central

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-01-01

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

  18. Insulin signaling in skeletal muscle and liver of neonatal pigs during endotoxemia

    USDA-ARS?s Scientific Manuscript database

    Sepsis has been associated with tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) overproduction, insulin resistance, and a profound suppression of muscle protein synthesis. However, lesser suppression of muscle protein synthesis in neonatal pigs occurs in response to endotoxin (LPS) whe...

  19. TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension.

    PubMed

    Huang, Fang; Ni, Min; Zhang, Jing-Ming; Li, Dong-Jie; Shen, Fu-Ming

    2017-04-01

    Angiotensin II (Ang II)-induced injury of vascular smooth muscle cells (VSMCs) serves an important role in hypertension and other cardiovascular disorders. Transient receptor potential melastatin 8 (TRPM8) is a thermally‑regulated Ca2+‑permeable channel that is activated by reduced body temperature. Although several recent studies have revealed the regulatory effect of TRPM8 in vascular tone and hypertension, the precise role of TRPM8 in dysfunction of vascular smooth muscle cells (VSMCs) induced by Ang II remains elusive. In the present study, the possible function of TRPM8 in Ang II‑induced VSMCs malfunction in vivo and in vitro was investigated. In the aortae from rats that had undergone a two‑kidney one‑clip operation, which is a widely‑used renovascular hypertension model, the mRNA and protein levels of TRPM8 were reduced. In addition, exogenous Ang II treatment decreased TRPM8 mRNA and protein expression levels in primary cultures of rat VSMCs. TRPM8 activation by menthol, a pharmacological agonist, in VSMCs, significantly attenuated the Ang II‑induced increase in reactive oxygen species and H2O2 production. In addition, TRPM8 activation reduced the Ang II‑induced upregulation of NADPH oxidase (NOX) 1 and NOX4 in VSMCs. Furthermore, TRPM8 activation relieved the Ang II‑induced activation of ras homolog gene family, member A‑rho associated protein kinase 2 and janus kinase 2 signaling pathways in VSMCs. In conclusion, the results presented in the current study indicated that TRPM8 downregulation by Ang II in VSMCs may be involved in hypertension.

  20. Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidase.

    PubMed

    Lake, B G; Ball, S E; Kao, J; Renwick, A B; Price, R J; Scatina, J A

    2002-10-01

    1. The metabolism of Zaleplon (CL-284,846; ZAL) has been studied in precision-cut human liver slices and liver cytosol preparations. 2. Human liver slices metabolized ZAL to a number of products including 5-oxo-ZAL (M2), N-desethyl-5-oxo-ZAL (M1) and N-desethyl-ZAL (DZAL), the latter metabolite being known to be formed by CYP3A forms. 3. Human liver cytosol preparations catalysed the metabolism of ZAL to M2. Kinetic analysis of three cytosol preparations revealed mean (+/- SEM) K(m) and V(max) of 93 +/- 18 mm and 317 +/- 241 pmol/min/mg protein, respectively. 4. Using 16 individual human liver cytosol preparations a 33-fold variability in the metabolism of 80 micro M ZAL to M2 was observed. Correlations were observed between M2 formation and the metabolism of the aldehyde oxidase substrates phenanthridine (r(2) = 0.774) and phthalazine (r(2) = 0.460). 5. The metabolism of 80 micro M ZAL to M2 in liver cytosol preparations was markedly inhibited by the aldehyde oxidase inhibitors chlorpromazine, promethazine, hydralazine and menadione. Additional kinetic analysis suggested that chlorpromazine and promethazine were non-competitive inhibitors of M2 formation with K(i) of 2.3 and 1.9 micro M, respectively. ZAL metabolism to M2 was also inhibited by cimetidine. 6. Incubations conducted with human liver cytosol and H(2)(18)O demonstrated that the oxygen atom incorporated into ZAL and DZAL to form M2 and M1, respectively, was derived from water and not from molecular oxygen. 7. In summary, by correlation analysis, chemical inhibition and H(2)(18)O incorporation studies, ZAL metabolism to M2 in human liver appears to be catalysed by aldehyde oxidase. With human liver slices, ZAL was metabolized to products dependent on both aldehyde oxidase and CYP3A forms.

  1. CF2 transcription factor is involved in the regulation of Mef2 RNA levels, nuclei number and muscle fiber size.

    PubMed

    Arredondo, Juan J; Vivar, Jorge; Laine-Menéndez, Sara; Martínez-Morentin, Leticia; Cervera, Margarita

    2017-01-01

    CF2 and Mef2 influence a variety of developmental muscle processes at distinct stages of development. Nevertheless, the exact nature of the CF2-Mef2 relationship and its effects on muscle building remain yet to be resolved. Here, we explored the regulatory role of CF2 in the Drosophila embryo muscle formation. To address this question and not having proper null CF2 mutants we exploited loss or gain of function strategies to study the contribution of CF2 to Mef2 transcription regulation and to muscle formation. Our data point to CF2 as a factor involved in the regulation of muscle final size and/or the number of nuclei present in each muscle. This function is independent of its role as a Mef2 collaborative factor in the transcriptional regulation of muscle-structural genes. Although Mef2 expression patterns do not change, reductions or increases in parallel in CF2 and Mef2 transcript abundance were observed in interfered and overexpressed CF2 embryos. Since CF2 expression variations yield altered Mef2 expression levels but with correct spatio-temporal Mef2 expression patterns, it can be concluded that only the mechanism controlling expression levels is de-regulated. Here, it is proposed that CF2 regulates Mef2 expression through a Feedforward Loop circuit.

  2. CF2 transcription factor is involved in the regulation of Mef2 RNA levels, nuclei number and muscle fiber size

    PubMed Central

    Laine-Menéndez, Sara; Martínez-Morentin, Leticia; Cervera, Margarita

    2017-01-01

    CF2 and Mef2 influence a variety of developmental muscle processes at distinct stages of development. Nevertheless, the exact nature of the CF2-Mef2 relationship and its effects on muscle building remain yet to be resolved. Here, we explored the regulatory role of CF2 in the Drosophila embryo muscle formation. To address this question and not having proper null CF2 mutants we exploited loss or gain of function strategies to study the contribution of CF2 to Mef2 transcription regulation and to muscle formation. Our data point to CF2 as a factor involved in the regulation of muscle final size and/or the number of nuclei present in each muscle. This function is independent of its role as a Mef2 collaborative factor in the transcriptional regulation of muscle-structural genes. Although Mef2 expression patterns do not change, reductions or increases in parallel in CF2 and Mef2 transcript abundance were observed in interfered and overexpressed CF2 embryos. Since CF2 expression variations yield altered Mef2 expression levels but with correct spatio-temporal Mef2 expression patterns, it can be concluded that only the mechanism controlling expression levels is de-regulated. Here, it is proposed that CF2 regulates Mef2 expression through a Feedforward Loop circuit. PMID:28617826

  3. Biomarkers of oxidative stress and tissue damage released by muscle and liver after a single bout of swimming exercise.

    PubMed

    Ramos, Dionizio; Martins, Eduarda Gabrielle; Viana-Gomes, Diego; Casimiro-Lopes, Gustavo; Salerno, Verônica P

    2013-05-01

    Both acute exercise and excessive training can cause oxidative stress. The resulting increase in free radicals and the inadequate response from antioxidant systems can lead to a framework of cellular damage. An association between affected tissue and the biomarkers of oxidative stress that appear in plasma has not been clearly established. The aim of this study was to evaluate the source of oxidative stress biomarkers found in the plasma of untrained rats after a single bout of swimming exercise at 2 different intensities: low intensity (SBLIE) or high intensity (SBHIE). Immediately after the exercise, aspartate transaminase (AST), alanine transaminase (ALT), γ-glutamyltransferase (GGT), and lactate dehydrogenase (LDH) were measured in plasma to characterize cell damage. Oxidative stress was assessed using protein carbonylation (PC), total antioxidant capacity (TAC), and thiobarbituric acid reactive substances (TBARS) quantified by malondialdehyde concentration. SBHIE raised levels of plasma AST (93%) and ALT (17%), and both exercise regimens produced an increase in GGT (7%) and LDH (∼55%). Plasma levels of PC and TBARS were greater in the SBHIE group; there were no changes in TAC. SBLIE caused only a modest increase in TBARS. In muscle, there were no changes in TAC, PC, or TBARS, regardless of exercise intensity, In the liver, TAC and TBARS increased significantly in both the SBLIE and SBHIE groups. This indicates that the oxidative stress biomarkers measured in the plasma immediately after a single bout of swimming exercise were generated primarily in the liver, not in muscle.

  4. Bioconcentration of (15)N-tamoxifen at environmental concentration in liver, gonad and muscle of Danio rerio.

    PubMed

    Orias, Frédéric; Simon, Laurent; Mialdea, Gladys; Clair, Angéline; Brosselin, Vanessa; Perrodin, Yves

    2015-10-01

    Pharmaceutical compounds (PCs) are ubiquitous in aquatic ecosystems. In addition to the direct ecotoxicological risk presented by certain PCs, others can accumulate inside organisms and along trophic webs, subsequently contaminating whole ecosystems. We studied the bioconcentration of a bioaccumulative PC already found several times in the environment: tamoxifen. To this end, we exposed Danio rerio for 21d to (15)N-tamoxifen concentrations ranging from 0.1 to 10µg/L and used an analytic method based on stable isotopes to evaluate the tamoxifen content in these organisms. The evolution of the (15)N/(14)N ratio was thus measured in liver, muscle and gonads of exposed fish compared to control fish. We succeeded in quantifying (15)N-tamoxifen bioconcentrations at all the exposure concentrations tested. The highest bioconcentration factors of tamoxifen measured were 14,920 in muscle, 73,800 in liver and 85,600 in gonads of fish after 21d exposure at a nominal concentration of 10µg/L. However, these bioconcentration factors have to be considered as maximal values (BCFMAX). Indeed, despite its proven stability, tamoxifen can be potentially partially degraded during experiments. We now need to refine these results by using a direct analytic method (i.e. LC-MS/MS).

  5. Muscle and liver protein synthesis in growing rats fed diets containing raw legumes as the main source of protein

    SciTech Connect

    Goena, M.; Santidrian, S.; Cuevillas, F.; Larralde, J.

    1986-03-01

    Although legumes are widely used as protein sources, their effects on protein metabolism remain quite unexplored. The authors have measured the rates of gastrocnemius muscle and liver protein synthesis in growing rats fed ad libitum over periods of 12 days on diets containing raw field bean (Vicia faba L.), raw kidney bean (Phaseolus vulgaris L.), and raw bitter vetch (Vicia ervilia L.) as the major sources of protein. Diets were isocaloric and contained about 12% protein. Protein synthesis was evaluated by the constant-intravenous-infusion method, using L-//sup 14/C/-tyrosine, as well as by the determination of the RNA-activity (g of newly synthesized protein/day/g RNA). Results showed that, as compared to well-fed control animals, those fed the raw legume diets exhibited a marked reduction in the rate of growth with no changes in the amount of food intake (per 100 g b.wt.). These changes were accompanied by a significant reduction in the rate of muscle protein synthesis in all legume-treated rats, being this reduction greater in the animals fed the Ph. vulgaris and V. ervilia diets. Liver protein synthesis was slightly higher in the rats fed the V. faba and V. ervilia diets, and smaller in the Ph. vulgaris-fed rats. It is suggested that both sulfur amino acid deficiency and the presence of different anti-nutritive factors in raw legumes may account for these effects.

  6. A Plasmodium Phospholipase Is Involved in Disruption of the Liver Stage Parasitophorous Vacuole Membrane

    PubMed Central

    Burda, Paul-Christian; Roelli, Matthias A.; Schaffner, Marco; Khan, Shahid M.; Janse, Chris J.; Heussler, Volker T.

    2015-01-01

    The coordinated exit of intracellular pathogens from host cells is a process critical to the success and spread of an infection. While phospholipases have been shown to play important roles in bacteria host cell egress and virulence, their role in the release of intracellular eukaryotic parasites is largely unknown. We examined a malaria parasite protein with phospholipase activity and found it to be involved in hepatocyte egress. In hepatocytes, Plasmodium parasites are surrounded by a parasitophorous vacuole membrane (PVM), which must be disrupted before parasites are released into the blood. However, on a molecular basis, little is known about how the PVM is ruptured. We show that Plasmodium berghei phospholipase, PbPL, localizes to the PVM in infected hepatocytes. We provide evidence that parasites lacking PbPL undergo completely normal liver stage development until merozoites are produced but have a defect in egress from host hepatocytes. To investigate this further, we established a live-cell imaging-based assay, which enabled us to study the temporal dynamics of PVM rupture on a quantitative basis. Using this assay we could show that PbPL-deficient parasites exhibit impaired PVM rupture, resulting in delayed parasite egress. A wild-type phenotype could be re-established by gene complementation, demonstrating the specificity of the PbPL deletion phenotype. In conclusion, we have identified for the first time a Plasmodium phospholipase that is important for PVM rupture and in turn for parasite exit from the infected hepatocyte and therefore established a key role of a parasite phospholipase in egress. PMID:25786000

  7. Three days of intermittent stretching after muscle disuse alters the proteins involved in force transmission in muscle fibers in weanling rats.

    PubMed

    Gianelo, M C S; Polizzelo, J C; Chesca, D; Mattiello-Sverzut, A C

    2016-02-01

    The aim of this study was to determine the effects of intermittent passive manual stretching on various proteins involved in force transmission in skeletal muscle. Female Wistar weanling rats were randomly assigned to 5 groups: 2 control groups containing 21- and 30-day-old rats that received neither immobilization nor stretching, and 3 test groups that received 1) passive stretching over 3 days, 2) immobilization for 7 days and then passive stretching over 3 days, or 3) immobilization for 7 days. Maximal plantar flexion in the right hind limb was imposed, and the stretching protocol of 10 repetitions of 30 s stretches was applied. The soleus muscles were harvested and processed for HE and picrosirius staining; immunohistochemical analysis of collagen types I, III, IV, desmin, and vimentin; and immunofluorescence labeling of dystrophin and CD68. The numbers of desmin- and vimentin-positive cells were significantly decreased compared with those in the control following immobilization, regardless of whether stretching was applied (P<0.05). In addition, the semi-quantitative analysis showed that collagen type I was increased and type IV was decreased in the immobilized animals, regardless of whether the stretching protocol was applied. In conclusion, the largest changes in response to stretching were observed in muscles that had been previously immobilized, and the stretching protocol applied here did not mitigate the immobilization-induced muscle changes. Muscle disuse adversely affected several proteins involved in the transmission of forces between the intracellular and extracellular compartments. Thus, the 3-day rehabilitation period tested here did not provide sufficient time for the muscles to recover from the disuse maladaptations in animals undergoing postnatal development.

  8. Three days of intermittent stretching after muscle disuse alters the proteins involved in force transmission in muscle fibers in weanling rats

    PubMed Central

    Gianelo, M.C.S.; Polizzelo, J.C.; Chesca, D.; Mattiello-Sverzut, A.C.

    2015-01-01

    The aim of this study was to determine the effects of intermittent passive manual stretching on various proteins involved in force transmission in skeletal muscle. Female Wistar weanling rats were randomly assigned to 5 groups: 2 control groups containing 21- and 30-day-old rats that received neither immobilization nor stretching, and 3 test groups that received 1) passive stretching over 3 days, 2) immobilization for 7 days and then passive stretching over 3 days, or 3) immobilization for 7 days. Maximal plantar flexion in the right hind limb was imposed, and the stretching protocol of 10 repetitions of 30 s stretches was applied. The soleus muscles were harvested and processed for HE and picrosirius staining; immunohistochemical analysis of collagen types I, III, IV, desmin, and vimentin; and immunofluorescence labeling of dystrophin and CD68. The numbers of desmin- and vimentin-positive cells were significantly decreased compared with those in the control following immobilization, regardless of whether stretching was applied (P<0.05). In addition, the semi-quantitative analysis showed that collagen type I was increased and type IV was decreased in the immobilized animals, regardless of whether the stretching protocol was applied. In conclusion, the largest changes in response to stretching were observed in muscles that had been previously immobilized, and the stretching protocol applied here did not mitigate the immobilization-induced muscle changes. Muscle disuse adversely affected several proteins involved in the transmission of forces between the intracellular and extracellular compartments. Thus, the 3-day rehabilitation period tested here did not provide sufficient time for the muscles to recover from the disuse maladaptations in animals undergoing postnatal development. PMID:26648091

  9. Nutrigenomic effects of glucosinolates on liver, muscle and distal kidney in parasite-free and salmon louse infected Atlantic salmon.

    PubMed

    Skugor, Stanko; Jodaa Holm, Helle; Bjelland, Anne Kari; Pino, Jorge; Evensen, Øystein; Krasnov, Aleksei; Wadsworth, Simon

    2016-12-12

    Reduction of Lepeophtheirus salmonis infection in Atlantic salmon achieved by glucosinolates (GLs) from Brassica plants was recently reported. However, wider application of functional feeds based on GLs requires better knowledge of their positive and adverse effects. Liver, distal kidney and muscle transcriptomes of salmon exposed to the extreme dose of GLs were profiled by microarray, while qPCR analysis followed up selected hepatic and renal responses under the extreme and moderate GLs dose during the L. salmonis challenge. Transcriptional analysis were complemented with measurements of organ indices, liver steatosis and plasma profiling, including indicators of cytolysis and bilirubin. Finally, the third trial was performed to quantify the effect of lower GLs doses on growth. The extreme GLs dose caused a decrease in hepatic fat deposition and growth, in line with microarray findings, which suggested tissue remodeling and reduction of cellular proliferation in the skeletal muscle and liver. Lower GLs inclusion levels in a follow-up trial did not show negative effects on growth. Microarray analysis of the distal kidney pointed to activation of anti-fibrotic responses under the overexposure. However, analyses of ALT, CK and AST enzymes in plasma provided no evidence of increased cytolysis and organ damage. Prevalent activation of phase-2 detoxification genes that occurred in all three tissues could be considered part of beneficial effects caused by the extreme dose of GLs. In addition, transcriptomic evidence suggested GLs-mediated iron and heme withdrawal response, including increased heme degradation in muscle (upregulation of heme oxygenase-1), decrease of its synthesis in liver (downregulation of porphobilinogen deaminase) and increased iron sequestration from blood (hepatic induction of hepcidin-1 and renal induction of intracellular storage protein ferritin). This response could be advantageous for salmon upon encountering lice, which depend on the host for

  10. Resistance training, and IGF involvement in the maintenance of muscle mass during the aging process.

    PubMed

    Adamo, Martin L; Farrar, Roger P

    2006-08-01

    Sarcopenia is the decline of muscle mass and strength with age. Sarcopenia leads to significant impairment in the ability to carry out normal daily function and thus there is a great need for interventions that will lead to muscle regeneration and repair in the aging population. Age-related sarcopenia in humans, characterized by loss of type I and type II muscle fibers and a decrease in fiber cross-sectional area primarily in type II fibers, can be attenuated by mechanical load on the muscle, which increases cross-sectional area of the remaining fibers, but does not restore fiber numbers characteristic of young muscle. Considerable evidence also implicates age-related declines in muscle insulin-like growth factor action in sarcopenia. IGF-I promotes myoblast proliferation, differentiation, and protein accretion in muscle through multiple signaling mechanisms, including the PI3-kinase, MAP kinase and calcineurin pathways. Exercise and injury induce increases in IGF-I, IGF-I receptors and IGF-I-activated signaling pathways. Although there is evidence that aging muscle retains the ability to synthesize IGF-I, there is also evidence that aging may be associated with attenuation of the ability of exercise to induce an isoform of IGF-I that promotes satellite cell proliferation. Moreover, aging muscle may be resistant to IGF-I, an effect that is reversed by exercise. However, it is clear that over-expression of IGF-I in muscle can protect against age-related sarcopenia.

  11. Rejection triggers liver transplant tolerance: Involvement of mesenchyme-mediated immune control mechanisms in mice.

    PubMed

    Morita, Miwa; Joyce, Daniel; Miller, Charles; Fung, John J; Lu, Lina; Qian, Shiguang

    2015-09-01

    Liver tolerance was initially recognized by the spontaneous acceptance of liver allografts in many species. The underlying mechanisms are not completely understood. However, liver transplant (LT) tolerance absolutely requires interferon (IFN)-γ, a rejection-associated inflammatory cytokine. In this study, we investigated the rejection of liver allografts deficient in the IFN-γ receptor and reveal that the liver graft is equipped with machineries capable of counterattacking the host immune response through a mesenchyme-mediated immune control (MMIC) mechanism. MMIC is triggered by T effector (Tef) cell-derived IFN-γ that drives expression of B7-H1 on graft mesenchymal cells leading to Tef cell apoptosis. We describe the negative feedback loop between graft mesenchymal and Tef cells that ultimately results in LT tolerance. Comparable elevations of T-regulatory cells and myeloid-derived suppressor cells were observed in both rejection and tolerance groups and were not dependent on IFN-γ stimulation, suggesting a critical role of Tef cell elimination in tolerance induction. We identify potent MMIC activity in hepatic stellate cells and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver, given that spontaneous acceptance of kidney allografts has been reported, although less commonly, probably reflecting variance in MMIC activity. MMIC may represent an important homeostatic mechanism that supports peripheral tolerance and could be a target for the prevention and treatment of transplant rejection. This study highlights that the graft is an active participant in the equipoise between tolerance and rejection and warrants more attention in the search for tolerance biomarkers. © 2015 by the American Association for the Study of Liver Diseases.

  12. Rejection Triggers Liver Transplant Tolerance: Involvements of Mesenchyme-Mediated Immune Control Mechanisms

    PubMed Central

    Morita, Miwa; Joyce, Daniel; Miller, Charles; Fung, John J.; Lu, Lina; Qian, Shiguang

    2015-01-01

    Liver tolerance was initially recognized by the spontaneous acceptance of liver allograft in many species. The underlying mechanisms are not completely understood. We have been inspired by an unexpected phenomenon that the liver transplant tolerance absolutely requires interferon (IFN)-γ, a rejection-associated inflammatory cytokine. In this study, we investigate the rejection of liver allografts deficient in IFN-γ receptor and reveal that the liver graft is equipped with machineries capable of counterattacking the host immune response through a mesenchyme-mediated immune control (MMIC) mechanism. MMIC is triggered by T effectors (Tef) cell-derived IFN-γ to drive the expression of B7-H1 on graft mesenchymal cells leading to Tef cell apoptosis. We describe the negative feedback loop between graft mesenchymal and Tef cells that ultimately results in liver transplant tolerance. Comparable elevations of T regulatory cells and myeloid-derived suppressor cells are seen in both rejection and tolerance groups, and are not dependent on IFN-γ stimulation, suggesting a critical role of Tef cell elimination in tolerance induction. We identify potent MMIC activity in hepatic stellate cells and liver sinusoidal endothelial cells. MMIC is unlikely exclusive to the liver, as spontaneous acceptance of kidney allografts has been reported, although less commonly, probably reflecting variance in MMIC activity. MMCI may represent an important homeostatic mechanism that supports peripheral tolerance, and could be a target for the prevention and treatment of transplant rejection. This study highlights that the graft is actively participant in the equipoise between tolerance and rejection and warrants more attention in the search for tolerance biomarkers. PMID:25998530

  13. Inhibition of rat brain tryptophan metabolism by ethanol withdrawal and possible involvement of the enhanced liver tryptophan pyrrolase activity.

    PubMed Central

    Badawy, A A; Punjani, N F; Evans, C M; Evans, M

    1980-01-01

    1. Chronic ethanol administration to rats was previously shown to enhance brain 5-hydroxytryptamine synthesis by increasing the availability of circulating tryptophan to the brain secondarily to the NAD(P)H-mediated inhibition of liver tryptophan pyrrolase activity. 2. At 24h after ethanol withdrawal, all the above effects were observed because liver [NAD(P)H] was still increased. By contrast, all aspects of liver and brain tryptophan metabolism were normal at 12 days after withdrawal. 3. At 7--9 days after withdrawal, brain 5-hydroxytryptamine synthesis was decreased, as was tryptophan availability to the brain. Liver tryptophan pyrrolase activity at these time-intervals was maximally enhanced. 4. Administration of nicotinamide during the withdrawal phase not only abolished the withdrawal-induced enhancement of tryptophan pyrrolase activity on day 8, but also maintained the inhibition previously caused by ethanol. Under these conditions, the withdrawal-induced decreases in brain 5-hydroxytryptamine synthesis and tryptophan availability to the brain were abolished, and both functions were enhanced. Nicotinamide alone exerted similar effects in control rats. 5. It is suggested that ethanol withdrawal inhibits brain 5-hydroxytryptamine synthesis by decreasing tryptophan availability to the brain secondarily to the enhanced liver tryptophan pyrrolase activity. 6. The results are discussed in relation to the possible involvement of 5-hydroxytryptamine in dependence on ethanol and other drugs. PMID:7195200

  14. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    PubMed Central

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  15. Evidence for the involvement of the CXCL12 system in the adaptation of skeletal muscles to physical exercise.

    PubMed

    Puchert, Malte; Adams, Volker; Linke, Axel; Engele, Jürgen

    2016-09-01

    The chemokine CXCL12 and its primary receptor, CXCR4, not only promote developmental myogenesis, but also muscle regeneration. CXCL12 chemoattracts CXCR4-positive satellite cells/blood-borne progenitors to the injured muscle, promotes myoblast fusion, partially with existing myofibers, and induces angiogenesis in regenerating muscles. Interestingly, the mechanisms underlying muscle regeneration are in part identical to those involved in muscular adaptation to intensive physical exercise. These similarities now prompted us to determine whether physical exercise would impact the CXCL12 system in skeletal muscle. We found that CXCL12 and CXCR4 are upregulated in the gastrocnemius muscle of rats that underwent a four-week period of constrained daily running exercise on a treadmill. Double-staining experiments confirmed that CXCL12 and CXCR4 are predominantly expressed in MyHC-positive muscle fibers. Moreover, these training-dependent increases in CXCL12 and CXCR4 expression also occurred in rats with surgical coronary artery occlusion, implying that the muscular CXCL12 system is still active in skeletal myopathy resulting from chronic heart failure. Expression of the second CXCL12 receptor, CXCR7, which presumably acts as a scavenger receptor in muscle, was not affected by training. Attempts to dissect the molecular events underlying the training-dependent effects of CXCL12 revealed that the CXCL12-CXCR4 axis activates anabolic mTOR-p70S6K signaling and prevents upregulation of the catabolic ubiquitin ligase MurF-1 in C2C12 myotubes, eventually increasing myotube diameters. Together, these findings point to a pivotal role of the CXCL12-CXCR4 axis in exercise-induced muscle maintenance and/or growth. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Extracellular signal-regulated kinase pathway is differentially involved in beta-agonist-induced hypertrophy in slow and fast muscles.

    PubMed

    Shi, H; Zeng, C; Ricome, A; Hannon, K M; Grant, A L; Gerrard, D E

    2007-05-01

    The molecular mechanisms controlling beta-adrenergic receptor agonist (BA)-induced skeletal muscle hypertrophy are not well known. We presently report that BA exerts a distinct muscle- and muscle fiber type-specific hypertrophy. Moreover, we have shown that pharmacologically or genetically attenuating extracellular signal-regulated kinase (ERK) signaling in muscle fibers resulted in decreases (P < 0.05) in fast but not slow fiber type-specific reporter gene expressions in response to BA exposure in vitro and in vivo. Consistent with these data, forced expression of MAPK phosphatase 1, a nuclear protein that dephosphorylates ERK1/2, in fast-twitch skeletal muscle ablated (P < 0.05) the hypertrophic effects of BA feeding (clenbuterol, 20 parts per million in water) in vivo. Further analysis has shown that BA-induced phosphorylation and activation of ERK occurred to a greater (P < 0.05) extent in fast myofibers than in slow myofibers. Analysis of the basal level of ERK activity in slow and fast muscles revealed that ERK1/2 is activated to a greater extent in fast- than in slow-twitch muscles. These data indicate that ERK signaling is differentially involved in BA-induced hypertrophy in slow and fast skeletal muscles, suggesting that the increased abundance of phospho-ERK1/2 and ERK activity found in fast-twitch myofibers, compared with their slow-twitch counterparts, may account, at least in part, for the fiber type-specific hypertrophy induced by BA stimulation. These data suggest that fast myofibers are pivotal in the adaptation of muscle to environmental cues and that the mechanism underlying this change is partially mediated by the MAPK signaling cascade.

  17. Facilitation handlings induce increase in electromyographic activity of muscles involved in head control of cerebral palsy children.

    PubMed

    Simon, Anelise de Saldanha; do Pinho, Alexandre Severo; Grazziotin Dos Santos, Camila; Pagnussat, Aline de Souza

    2014-10-01

    This study aimed to investigate the electromyographic (EMG) activation of the main cervical muscles involved in the head control during two postures widely used for the facilitation of head control in children with Cerebral Palsy (CP). A crossover trial involving 31 children with clinical diagnosis of CP and spastic quadriplegia was conducted. Electromyography was used to measure muscular activity in randomized postures. Three positions were at rest: (a) lateral decubitus, (b) ventral decubitus on the floor and (c) ventral decubitus on the wedge. Handlings for facilitating the head control were performed using the hip joint as key point of control in two postures: (a) lateral decubitus and (b) ventral decubitus on wedge. All children underwent standardized handlings, performed by the same researcher with experience in the neurodevelopmental treatment. EMG signal was recorded from muscles involved in the head control (paraspinal and sternocleidomastoid muscles) in sagittal, frontal and transverse planes, at the fourth cervical vertebra (C4), tenth thoracic vertebra (T10) and sternocleidomastoid muscle (SCM) levels. The results showed a significant increase in muscle activation when handling was performed in the lateral decubitus at C4 (P<0.001), T10 (P<0.001) and SCM (P=0.02) levels. A significant higher muscle activation was observed when handling was performed in lateral decubitus when compared to ventral decubitus at C4 level (P<0.001). Handling in ventral decubitus also induced an increase in EMG activation at T10 (P=0.018) and SCM (P=0.004) levels but not at C4 level (P=0.38). In conclusion, handlings performed in both positions may induce the facilitation of head control, as evaluated by the activity of cervical and upper trunk muscles. Handling performed in lateral decubitus may induce a slightly better facilitation of head control. These findings contribute to evidence-based physiotherapy practice for the rehabilitation of severely spastic quadriplegic CP

  18. Variation in metabolic enzymatic activity in white muscle and liver of blue tilapia, Oreochromis aureus, in response to long-term thermal acclimatization

    NASA Astrophysics Data System (ADS)

    Younis, Elsayed M.

    2015-05-01

    The effects of rearing temperature on white muscle and hepatic phosphofructokinase (PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined in fingerlings of blue tilapia, Oreochromis aureus. The experiment was conducted for 14 weeks at temperatures of 18, 22, 26, 30, and 34°C. The activity of the glycolytic enzymes PFK, PK, and LDH in white muscle increased significantly with increase in water temperature. A reverse trend was observed for these enzymes in the liver, except for LDH, which behaved in the same manner as in white muscle. Cytosolic AST and ALT activity increased in both white muscle and liver in response to warm thermal acclimatization, while a reduction in mitochondrial AST and ALT activity was noticed at high temperatures in comparison with those at a lower temperature.

  19. The Content of Copper and Molybdenum in the Liver, Kidneys, and Skeletal Muscles of Elk (Alces alces) from North-Eastern Poland.

    PubMed

    Skibniewski, Michał; Skibniewska, Ewa M; Kośla, Tadeusz; Olbrych, Katarzyna

    2016-02-01

    The aim of the study was to evaluate the content of Cu and Mo in the liver, kidneys, and skeletal muscles of elks from north-eastern Poland. The investigation material comprised samples obtained in 2010 from 35 animals. Animals were grouped according to age (elks up to 2 years and over than 3 years). The metal concentrations were determined using coupled plasma-mass spectrometry (ICP-MS) method. The mean Cu concentrations in the liver, kidneys, and skeletal muscles were 23.08, 5.03, and 2.36 mg∙kg(-1) wet weight, respectively. The mean Mo content in the examined samples was as follows: 0.92, 0.42, and 0.05 mg∙kg(-1) wet weight (w.w.) in the liver, kidneys, and muscles. In the analysis of correlation between the Cu and Mo levels in particular organs, the presence of significant dependence (p ≤ 0.05) was observed in the liver of animals studied. The mean Cu content in the liver of animals studied is lower compared with data reported from Sweden, Russia, and North America. Concentrations of Cu and Mo in the kidneys and skeletal muscles of Polish elks are similar to data noted in healthy animals from Scandinavian region. The results suggest that elks from north-eastern Poland may be threatened by primary Cu deficiency.

  20. Rules of tissue packing involving different cell types: human muscle organization.

    PubMed

    Sánchez-Gutiérrez, Daniel; Sáez, Aurora; Gómez-Gálvez, Pedro; Paradas, Carmen; Escudero, Luis M

    2017-01-10

    Natural packed tissues are assembled as tessellations of polygonal cells. These include skeletal muscles and epithelial sheets. Skeletal muscles appear as a mosaic composed of two different types of cells: the "slow" and "fast" fibres. Their relative distribution is important for the muscle function but little is known about how the fibre arrangement is established and maintained. In this work we capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that the biceps brachii muscle presents a particular arrangement, based on the different sizes of slow and fast fibres. By contrast, in the quadriceps muscle an unbiased distribution exists. Our results indicate that the relative size of each cellular type imposes an intrinsic organization into natural tessellations. These findings establish a new framework for the analysis of any packed tissue where two or more cell types exist.

  1. Rules of tissue packing involving different cell types: human muscle organization

    PubMed Central

    Sánchez-Gutiérrez, Daniel; Sáez, Aurora; Gómez-Gálvez, Pedro; Paradas, Carmen; Escudero, Luis M.

    2017-01-01

    Natural packed tissues are assembled as tessellations of polygonal cells. These include skeletal muscles and epithelial sheets. Skeletal muscles appear as a mosaic composed of two different types of cells: the “slow” and “fast” fibres. Their relative distribution is important for the muscle function but little is known about how the fibre arrangement is established and maintained. In this work we capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that the biceps brachii muscle presents a particular arrangement, based on the different sizes of slow and fast fibres. By contrast, in the quadriceps muscle an unbiased distribution exists. Our results indicate that the relative size of each cellular type imposes an intrinsic organization into natural tessellations. These findings establish a new framework for the analysis of any packed tissue where two or more cell types exist. PMID:28071729

  2. Involvement of Mouse Constitutive Androstane Receptor in Acifluorfen-Induced Liver Injury and Subsequent Tumor Development.

    PubMed

    Kuwata, Kazunori; Inoue, Kaoru; Ichimura, Ryohei; Takahashi, Miwa; Kodama, Yukio; Shibutani, Makoto; Yoshida, Midori

    2016-06-01

    Acifluorfen (ACI), a protoporphyrinogen oxidase (PROTOX) inhibitor herbicide, promotes the accumulation of protoporphyrin IX (PPIX), and induces tumors in the rodent liver. Porphyria is a risk factor for liver tumors in humans; however, the specific mechanisms through which ACI induces hepatocarcinogenesis in rodents are unclear. Here, we investigated the mode of action of ACI-induced hepatocarcinogenesis, focusing on constitutive androstane receptor (CAR, NR1I3), which is essential for the development of rodent liver tumors in response to certain cytochrome P450 (CYP) 2B inducers. Dietary treatment with 2500 ppm ACI for up to 13 weeks increased Cyp2b10 expression in the livers of wild-type (WT) mice, but not in CAR-knockout (CARKO) mice. Microscopically, ACI treatment-induced cytotoxic changes, including hepatocellular necrosis and inflammation, and caused regenerative changes accompanied by prolonged increases in the numbers of proliferating cell nuclear antigen-positive hepatocytes in WT mice. In contrast, these cytotoxic and regenerative changes in hepatocytes were significantly attenuated, but still observed, in CARKO mice. ACI treatment also increased liver PPIX levels similarly in both genotypes; however, no morphological evidence of porphyrin deposition was found in hepatocytes from either genotype. Treatment with 2500 ppm ACI for 26 weeks after initiation with diethylnitrosamine increased the incidence and multiplicities of altered foci and adenomas in hepatocytes from WT mice; these effects were significantly reduced in CARKO mice. These results indicated that prolonged cytotoxicity in the liver was a key factor for ACI-induced hepatocarcinogenesis, and that CAR played an important role in ACI-induced liver injury and tumor development in mice.

  3. Effect of long-term optional ingestion of canola oil, grape seed oil, corn oil and yogurt butter on serum, muscle and liver cholesterol status in rats.

    PubMed

    Asadi, Farzad; Shahriari, Ali; Chahardah-Cheric, Marjan

    2010-01-01

    The aim of the present study was to determine the effect of long-term optional intake of vegetable oils (canola, grape seed, corn) and yogurt butter on the serum, liver and muscle cholesterol status. Twenty-five male Wistar rats were randomly categorized into five groups (n=5) as follows: control, canola oil, grape seed oil, corn oil and manually prepared yogurt butter. In each group, 24h two bottle choice (oil and water) tests were performed for 10 weeks. Serum cholesterol values showed a trend to decrease in grape seed oil, corn oil and yogurt butter groups compared to the control. Optional intake of yogurt butter made a significant increase in HDL-C values (42.34+/-9.98 mg/dL) yet decrease in LDL-C values (11.68+/-2.06 mg/dL) compared to the corresponding control (19.07+/-3.51; 30.96+/-6.38 mg/dL, respectively). Furthermore, such findings were concomitant with a significant decrease in the liver TC levels (1.75+/-0.31 mg/g liver) and an increase in the muscle TC levels (1.85+/-0.32 mg/g liver) compared to the corresponding control (2.43+/-0.31; 0.94+/-0.14 mg/g liver, respectively). Optional intake of manually prepared yogurt butter has more beneficial effects on serum lipoprotein cholesterol values with some alterations in the liver and muscle cholesterol states than the vegetable oils.

  4. Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element.

    PubMed

    Kiyosue, Arihiro; Nagata, Daisuke; Myojo, Masahiro; Sato, Tomohiko; Takahashi, Masao; Satonaka, Hiroshi; Nagai, Ryozo; Hirata, Yasunobu

    2011-12-01

    Osteopontin (OPN) is known to be one of the cytokines that is involved in the vascular inflammation caused by aldosterone (Aldo). Previous reports have shown that Aldo increases OPN transcripts, and the mechanisms for this remain to be clarified. In this study, we investigated how Aldo increases OPN transcripts in the vascular smooth muscle cells of rats. Aldosterone increased OPN transcripts time-dependently as well as dose-dependently. This increase was diminished by eplerenone, a mineralocorticoid receptor (MR) antagonist. Luciferase promoter assays showed that the OPN promoter deleted to the -1599 site retained the same promoting ability as the full-length OPN promoter when stimulated by 10(-7) M Aldo, but the promoter deleted to the -1300 site lost the promoting ability. A glucocorticoid response element (GRE) is located in that deleted region. Luciferase assays of a mutated promoter without the GRE lost the luciferase upregulation, although mutated promoters with the deletion of other consensus sites maintained the promoter activity. The binding of the Aldo-MR complex to the GRE fragment was confirmed by an electrophoretic-mobility shift assay. This is the first report showing that Aldo regulates the transcriptional levels of OPN and inflammatory responses in the vasculature through a specific GRE site in the OPN promoter region.

  5. Insulin-independent GLUT4 translocation in proliferative vascular smooth muscle cells involves SM22α.

    PubMed

    Zhao, Li-Li; Zhang, Fan; Chen, Peng; Xie, Xiao-Li; Dou, Yong-Qing; Lin, Yan-Ling; Nie, Lei; Lv, Pin; Zhang, Dan-Dan; Li, Xiao-Kun; Miao, Sui-Bing; Yin, Ya-Juan; Dong, Li-Hua; Song, Yu; Shu, Ya-Nan; Han, Mei

    2017-02-01

    The insulin-sensitive glucose transporter 4 (GLUT4) is a predominant facilitative glucose transporter in vascular smooth muscle cells (VSMCs) and is significantly upregulated in rabbit neointima. This study investigated the role of GLUT4 in VSMC proliferation, the cellular mechanism underlying PDGF-BB-stimulated GLUT4 translocation, and effects of SM22α, an actin-binding protein, on this process. Chronic treatment of VSMCs with PDGF-BB significantly elevated GLUT4 expression and glucose uptake. PDGF-BB-induced VSMC proliferation was dependent on GLUT4-mediated glucose uptake. Meanwhile, the response of GLUT4 to insulin decreased in PDGF-BB-stimulated VSMCs. PDGF-BB-induced GLUT4 translocation partially rescued glucose utilization in insulin-resistant cells. Immunofluorescence and western blot analysis revealed that PDGF-BB induced GLUT4 translocation in an actin dynamics-dependent manner. SM22α disruption facilitated GLUT4 translocation and glucose uptake by promoting actin dynamics and cortical actin polymerization. Similar results were observed in VSMCs of SM22α (-/-) mice. The in vivo experiments showed that the glucose level in the neointima induced by ligation was significantly increased in SM22α (-/-) mice, accompanied by increased neointimal thickness, compared with those in wild-type mice. These findings suggest that GLUT4-mediated glucose uptake is involved in VSMC proliferation, and provide a novel link between SM22α and glucose utilization in PDGF-BB-triggered proliferation.

  6. Identification of Annexin A4 as a hepatopancreas factor involved in liver cell survival

    PubMed Central

    Zhang, Danhua; Golubkov, Vladislav S.; Han, Wenlong; Correa, Ricardo G.; Zhou, Ying; Lee, Sunyoung; Strongin, Alex Y.; Dong, P. Duc Si

    2014-01-01

    To gain insight into liver and pancreas development, we investigated the target of 2F11, a monoclonal antibody of unknown antigen, widely used in zebrafish studies for labeling hepatopancreatic ducts. Utilizing mass spectrometry and in vivo assays, we determined the molecular target of 2F11 to be Annexin A4 (Anxa4), a calcium binding protein. We further found that in both zebrafish and mouse endoderm, Anxa4 is broadly expressed in the developing liver and pancreas, and later becomes more restricted to the hepatopancreatic ducts and pancreatic islets, including the insulin producing β-cells. Although Anxa4 is a known target of several monogenic diabetes genes and its elevated expression is associated with chemoresistance in malignancy, its in vivo role is largely unexplored. Knockdown of Anxa4 in zebrafish leads to elevated expression of caspase 8 and Δ113p53, and liver bud specific activation of Caspase 3 and apoptosis. Mosaic knockdown reveal that Anxa4 is required cell-autonomously in the liver bud for cell survival. This finding is further corroborated with mosaic anxa4 knockout studies using the CRISPR/Cas9 system. Collectively, we identify Anxa4 as a new, evolutionarily conserved hepatopancreatic factor that is required in zebrafish for liver progenitor viability, through inhibition of the extrinsic apoptotic pathway. A role for Anxa4 in cell survival may have implications for the mechanism of diabetic β-cell apoptosis and cancer cell chemoresistance. PMID:25176043

  7. Liver irradiation in stage IIIA Hodgkin's disease patients with splenic involvement

    SciTech Connect

    Lee, C.K.; Bloomfield, C.D.; Levitt, S.H.

    1984-04-01

    Curative treatment for Hodgkin's disease for patients who are pathology-staged IIIA, spleen-positive, consisted of total nodal irradiation (TNI) alone at the University of Minnesota Hospitals prior to 1975. This approach has been modified since 1975 to give low-dose irradiation to the liver in addition to TNI because of the high recurrence rate with TNI alone. Recurrence-free survival improved significantly when the liver was irradiated as compared to results with TNI alone (78% vs. 41% at 5 years, p . 0.004). The 5-year, overall survival was not significantly different in the two groups (90% vs. 80% at 5 years, p . 0.373). Various prognostic factors were examined. Patients who received liver treatment had statistically significant improvement in recurrence-free survival as compared to patients who did not receive liver treatment in the following categories: anatomic substage IIIA1, histologic classification of nodular sclerosis, male gender, age less than 40, number of primary sites, and extent of splenic disease. However, these factors failed to show clinical significance as prognostic factors. We conclude that TNI with low-dose liver irradiation should be used as the primary modality of treatment of Hodgkin's disease, pathology-staged IIIA patients. We conclude that chemotherapy should be reserved for recurrences in view of the excellent current results and the lesser risk from treatment, especially the risk of carcinogenesis.

  8. Anatomic localization of motor points for the neuromuscular blockade of hand intrinsic muscles involved in thumb-in-palm.

    PubMed

    Im, Sun; Han, Seung Ho; Choi, Jin Hwan; Lee, Je Hoon; Ko, Young Jin; Lee, Jong In; Kim, Hye Won

    2008-09-01

    To determine the location of the motor points and intramuscular branches for the muscles involved in thumb-in-palm and the abductor pollicis brevis muscle, the latter of which, because of its anatomic proximity, may be inadvertently blocked. Hand intrinsic muscles from 20 fresh cadavers were dissected. The point of nerve entry to the muscle belly and the points where the intramuscular endings were located most proximally and distally were defined in relation to a reference line connecting the hook of hamate and the head of the first metacarpal bone. We were able to define a region, located from 66.08% +/- 8.67% to 70.28% +/- 10.62% of the reference line, with the hook of hamate as starting point, where intramuscular endings for the thumb-in-palm muscles were dense and farther from the intramuscular endings for the abductor pollicis brevis. The region around 40% of the reference line was the point where the intramuscular endings were most dense for the abductor pollicis brevis. The results may provide guidelines that could help in localizing the appropriate points for the neuromuscular blockade of thumb-in-palm muscles and, at the same time, help in minimizing the inadvertent block of the abductor pollicis brevis.

  9. The constitutive active/androstane receptor facilitates unique phenobarbital-induced expression changes of genes involved in key pathways in precancerous liver and liver tumors.

    PubMed

    Phillips, Jennifer M; Burgoon, Lyle D; Goodman, Jay I

    2009-08-01

    Our overall goal is to elucidate progressive changes, in expression and methylation status, of genes which play key roles in phenobarbital (PB)-induced liver tumorigenesis, with an emphasis on their potential to affect signaling through critical pathways involved in the regulation of cell growth and differentiation. PB-elicited unique expression changes of genes, including some of those identified previously as exhibiting regions of altered DNA methylation, were discerned in precancerous liver tissue and/or individual liver tumors from susceptible constitutive active/androstane receptor (CAR) wild-type (WT) compared with resistant CAR knockout (KO) mice. Many of these function in crucial cancer-related processes, for example, angiogenesis, apoptosis, cell cycle, DNA methylation, Hedgehog signaling, invasion/metastasis, Notch signaling, and Wnt signaling. Furthermore, a subset of the uniquely altered genes contained CAR response elements (CAREs). This included Gadd45b, a coactivator of CAR and inhibitor of apoptosis, and two DNA methyltransferases (Dnmt1, Dnmt3a). The presence of CAREs in Dnmts suggests a potential direct link between PB and altered DNA methylation. The current data are juxtaposed with the effects of PB on DNA methylation and gene expression which occurred uniquely in liver tumor-prone B6C3F1 mice, as compared with the resistant C57BL/6, following 2 or 4 weeks of treatment. Collectively, these data reveal a comprehensive view of PB-elicited molecular alterations (i.e., changes in gene expression and DNA methylation) that can facilitate hepatocarcinogenesis. Notably, candidate genes for initial "fingerprints" of early and late stages of PB-induced tumorigenesis are proposed.

  10. The Constitutive Active/Androstane Receptor Facilitates Unique Phenobarbital-Induced Expression Changes of Genes Involved in Key Pathways in Precancerous Liver and Liver Tumors

    PubMed Central

    Phillips, Jennifer M.; Burgoon, Lyle D.; Goodman, Jay I.

    2009-01-01

    Our overall goal is to elucidate progressive changes, in expression and methylation status, of genes which play key roles in phenobarbital (PB)–induced liver tumorigenesis, with an emphasis on their potential to affect signaling through critical pathways involved in the regulation of cell growth and differentiation. PB-elicited unique expression changes of genes, including some of those identified previously as exhibiting regions of altered DNA methylation, were discerned in precancerous liver tissue and/or individual liver tumors from susceptible constitutive active/androstane receptor (CAR) wild-type (WT) compared with resistant CAR knockout (KO) mice. Many of these function in crucial cancer-related processes, for example, angiogenesis, apoptosis, cell cycle, DNA methylation, Hedgehog signaling, invasion/metastasis, Notch signaling, and Wnt signaling. Furthermore, a subset of the uniquely altered genes contained CAR response elements (CAREs). This included Gadd45b, a coactivator of CAR and inhibitor of apoptosis, and two DNA methyltransferases (Dnmt1, Dnmt3a). The presence of CAREs in Dnmts suggests a potential direct link between PB and altered DNA methylation. The current data are juxtaposed with the effects of PB on DNA methylation and gene expression which occurred uniquely in liver tumor-prone B6C3F1 mice, as compared with the resistant C57BL/6, following 2 or 4 weeks of treatment. Collectively, these data reveal a comprehensive view of PB-elicited molecular alterations (i.e., changes in gene expression and DNA methylation) that can facilitate hepatocarcinogenesis. Notably, candidate genes for initial “fingerprints” of early and late stages of PB-induced tumorigenesis are proposed. PMID:19482888

  11. Determination of cytochrome P450 enzymes involved in the metabolism of (-)-terpinen-4-ol by human liver microsomes.

    PubMed

    Miyazawa, M; Haigou, R

    2011-12-01

    The in vitro metabolism of (-)-terpinen-4-ol was examined in human liver microsomes and recombinant enzymes. The biotransformation of (-)-terpinen-4-ol was investigated by gas chromatography-mass spectrometry. (-)-Terpinen-4-ol was found to be oxidized to (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol, major metabolic product by human liver microsomal P450 enzymes. The formation of metabolites of (-)-terpinen-4-ol was determined by relative abundance of mass fragments and retention times on GC. CYP2A6 in human liver microsomes was a major enzyme involved in the oxidation of (-)-terpinen-4-ol by human liver microsomes, based on the following lines of evidence. First, of 11 recombinant human P450 enzymes tested, CYP2A6 had the highest activity for oxidation of (-)-terpinen-4-ol. Second, oxidation of (-)-terpinen-4-ol was inhibited by (+)-menthofuran. Finally, there was a good correlation between CYP2A6 maker activity and (-)-terpinen-4-ol oxidation activities in liver microsomes of 10 human samples. Kinetic analysis showed that the V(max)/K(m) values for (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol catalysed by liver microsomes of human sample HH-18 was 2.49 μL/min/nmol. Human recombinant CYP2A6 catalysed (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol with V(max) values of 13.9 nmol/min/nmol P450 and apparent K(m) values of 91 μM.

  12. Fluoride-induced oxidative stress is involved in the morphological damage and dysfunction of liver in female mice.

    PubMed

    Zhou, Bian-hua; Zhao, Jing; Liu, Jeffrey; Zhang, Ji-liang; Li, Jian; Wang, Hong-wei

    2015-11-01

    Fluoride (F), one of the most toxic environmental and industrial pollutants, is known to exert hepatotoxicity. The contribution of oxidative stress to the F tolerance of liver remains largely unknown. In this study, the morphological and ultrastructural characteristics of liver were observed using hematoxylin and eosin staining and transmission electron microscopy (TEM), respectively. Oxidative-stress participations was analysed and the mRNA expression levels of catalase (Cat), glutathione peroxidase 1 (GSH-Px1), nitric oxide synthase 2 (NOS2), and superoxide dismutase 1 (SOD1) were investigated by real-time PCR. Changes in liver-function parameters were also detected. Results showed that the reactive content of reactive oxygen species increased significantly, whereas SOD and GSH-Px activities, as well as total anti-oxidising capability (T-AOC), decreased significantly, with increased nitric oxide (NO) and malondialdehyde (MDA) contents in liver and serum after 70days of F treatment. The mRNA expression levels of Cat, GSH-Px1, and SOD were significantly downregulated, whereas NOS2 mRNA expression level was up upregulated, after F treatment for 70days. Light microscopy also revealed that hepatocytes were fused into pieces; cell boundaries were unclear, and nuclei were lightly stained. TEM further showed that hepatocytes were characterised by vague nuclear and mitochondrial membranes, dilated endoplasmic reticulum, and aggravated vacuolar degeneration. Activities of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase, as well as the level of total bilirubin in serum increased. Overall, these results indicated that F interfered with the balance of antioxidase activity and morphological changes in liver, which were involved in mouse liver dysfunction.

  13. Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes.

    PubMed

    Yoshii, K; Kobayashi, K; Tsumuji, M; Tani, M; Shimada, N; Chiba, K

    2000-01-01

    Studies to identify the cytochrome P450 (CYP) isoform(s) involved in chlorpromazine 7-hydroxylation were performed using human liver microsomes and cDNA-expressed human CYPs. The kinetics of chlorpromazine 7-hydroxylation in human liver microsomes showed a simple Michaelis-Menten behavior. The apparent Km and Vmax values were 3.4+/-1.0 microM and 200.5+/-83.7 pmol/min/mg, respectively. The chlorpromazine 7-hydroxylase activity in human liver microsomes showed good correlations with desipramine 2-hydroxylase activity (r = 0.763, p < 0.05), a marker activity for CYP2D6, and phenacetin O-deethylase activity (r = 0.638, p < 0.05), a marker activity for CYP1A2. Quinidine (an inhibitor of CYP2D6) completely inhibited while alpha-naphthoflavone (an inhibitor of CYP1A2) marginally inhibited the chlorpromazine 7-hydroxylase activity in a human liver microsomal sample showing high CYP2D6 activity. On the other hand, alpha-naphthoflavone inhibited the chlorpromazine 7-hydroxylase activity to 55-65% of control in a human liver microsomal sample showing low CYP2D6 activity. Among eleven cDNA-expressed CYPs studied, CYP2D6 and CYP1A2 exhibited significant activity for the chlorpromazine 7-hydroxylation. The Km values for the chlorpromazine 7-hydroxylation of both cDNA-expressed CYP2D6 and CYP1A2 were in agreement with the Km values of human liver microsomes. These results suggest that chlorpromazine 7-hydroxylation is catalyzed mainly by CYP2D6 and partially by CYP1A2.

  14. Proinflammatory Liver and Antiinflammatory Intestinal Mediators Involved in Portal Hypertensive Rats

    PubMed Central

    Aller, Maria Angeles; Vara, Elena; Garcia, Cruz; Palma, Maria Dolores; Arias, Jorge L.; Nava, Maria Paz; Arias, Jaime

    2005-01-01

    Proinflammatory (TNF-α, IL-1β, and NO) and antiinflammatory (IL-10, CO) levels were assayed in serum, liver, and small bowel in order to verify a hypothetic inflammatory etiopathogeny of portal hypertension that could be the cause of its evolutive heterogeneity. Male Wistar rats were divided into one control group (n = 11) and one group with a triple stenosing ligation of the portal vein (n = 23) after 28 days of evolution. In one subgroup of portal hypertensive rats, portal pressure, collateral venous circulation, mesenteric vasculopathy, and liver and spleen weights were determined. In the remaining rats with portal hypertension TNF-α, IL-1β, and IL-10 were quantified in liver and ileum by enzyme-linked immunosorbent assay. NO synthase activity was studied in liver and ileum. CO and NO were measured in portal and systemic blood by spectrophotometry and Griess reaction, respectively. Portal hypertensive rats with mayor spleen weight show hepatomegaly and mayor development of collateral circulation. Ileum release of IL-10 (0.30 ± 0.12 versus 0.14 ± 0.02 pmol/mg protein; P < .01) is associated with a liver production of both proinflammatory mediators (TNF-α: 2 ± 0.21 versus 1.32 ± 0.60 pmol/mg protein; P < .05, IL-1β: 19.17 ± 2.87 versus 5.96 ± 1.84 pmol/mg protein; P = .005, and NO: 132.10 ± 34.72 versus 61.05 ± 8.30 nmol/mL; P = .005) and an antiinflammatory mediator (CO: 6.49 ± 2.99 versus 3.03 ± 1.59 pmol/mL; P = .005). In short-term prehepatic portal hypertension a gut-liver inflammatory loop, which could be fundamental in the regulation both of the portal pressure and of its complications, could be proposed. PMID:16030393

  15. Reactive oxygen species and calcium signals in skeletal muscle: A crosstalk involved in both normal signaling and disease.

    PubMed

    Espinosa, Alejandra; Henríquez-Olguín, Carlos; Jaimovich, Enrique

    2016-09-01

    Reactive Oxygen Species (ROS) have been profusely studied as agents of potential damage to living cells and they have been related to a number of pathological processes. Increasing evidence points to a more positive role of ROS in cell signaling and the detailed mechanism that regulates the precise amount of ROS needed for cell functioning without the deleterious effects of excess ROS still needs to be resolved in detail. In skeletal muscle the main source of ROS during normal functioning appears to be NADPH oxidase 2 (NOX2), which is activated by electrical stimuli (or exercise) through a cascade of events that include ATP release through pannexin1 channels. NOX2 is a protein complex that assembles in the T-tubule membrane before activation and ROS production by NOX2 appears to be important for muscle adaptation through gene expression and mitochondrial biogenesis as well as for improving glucose transport after insulin action. Excess ROS production (or diminished antioxidant defenses) plays a role in a number of pathological processes in skeletal muscle. Together with increased reactive nitrogen species, an increase in ROS appears to have a deleterious role in a model of Duchenne muscular dystrophy as well as muscle wasting in other diseases such as aging sarcopenia and cancer cachexia. In addition, ROS is involved in obesity and muscle insulin resistance, both of which are causally related to type 2 diabetes. A detailed description of the fine-tuning of ROS (including all sources of ROS) in skeletal muscle in health and disease will significantly contribute to our knowledge of both muscle adaptation and muscle related pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Differences of glycolysis in skeletal muscle and lactate metabolism in liver between plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae).

    PubMed

    Sun, Sheng-Zhen; Wei, Lian; Wei, Deng-Bang; Wang, Duo-Wei; Ma, Ben-Yuan

    2013-06-25

    The plateau pika (Ochotona curzoniae) and plateau zokor (Myospalax baileyi) are specialized native species of the Qinghai-Tibetan plateau. The goal of this study was to examine physiological differences in skeletal muscle glycolysis and hepatic lactate metabolism between these two species. The partial sequence of pyruvate carboxylase (PC) gene was cloned and sequenced. The mRNA expression levels of PC and lactate dehydrogenases (LDH-A, LDH-B) were determined by real-time PCR. The enzymatic activity of PC was measured using malic acid coupling method. The concentration of lactic acid (LD) and the specific activities of LDH in liver and skeletal muscle of two species were measured. The different isoenzymes of LDH were determined by native polyacrylamide gel electrophoresis (PAGE). The results showed that, (1) LDH-B mRNA level in skeletal muscle of plateau zokor was significantly higher than that of plateau pika (P < 0.01), but no differences was found at LDH-A mRNA levels between them (P > 0.05); (2) PC, LDH-A and LDH-B mRNA levels in liver of plateau pika were significantly higher than those of plateau zokor (P < 0.01); (3) The LDH activity and concentration of LD in skeletal muscle and liver, as well as the PC activity in liver of plateau pika were significantly higher than those of plateau zokor (P < 0.01); (4) The isoenzymatic spectrum of lactate dehydrogenase showed that the main LDH isoenzymes were LDH-A4, LDH-A3B and LDH-A2B2 in skeletal muscle of plateau pika, while the main LDH isoenzymes were LDH-AB3 and LDH-B4 in skeletal muscle of plateau zokor; the main isoenzymes were LDH-A3B, LDH-A2B2, LDH-AB3 and LDH-B4 in liver of plateau pika, while LDH-A4 was the only isoenzyme in liver of plateau zokor. These results indicate that the plateau pika gets most of its energy for sprint running through enhancing anaerobic glycolysis, producing more lactate in their skeletal muscle, and converting lactate into glucose and glycogen in the liver by enhancing

  17. The High Level of Aberrant Splicing of ISCU in Slow-Twitch Muscle May Involve the Splicing Factor SRSF3

    PubMed Central

    Österman, Lennart; Lindsten, Hans; Holmberg, Monica

    2016-01-01

    Hereditary myopathy with lactic acidosis (HML) is an autosomal recessive disease caused by an intronic one-base mutation in the iron-sulfur cluster assembly (ISCU) gene, resulting in aberrant splicing. The incorrectly spliced transcripts contain a 100 or 86 bp intron sequence encoding a non-functional ISCU protein, which leads to defects in several Fe-S containing proteins in the respiratory chain and the TCA cycle. The symptoms in HML are restricted to skeletal muscle, and it has been proposed that this effect is due to higher levels of incorrectly spliced ISCU in skeletal muscle compared with other energy-demanding tissues. In this study, we confirm that skeletal muscle contains the highest levels of incorrect ISCU splice variants compared with heart, brain, liver and kidney using a transgenic mouse model expressing human HML mutated ISCU. We also show that incorrect splicing occurs to a significantly higher extent in the slow-twitch soleus muscle compared with the gastrocnemius and quadriceps. The splicing factor serine/arginine-rich splicing factor 3 (SRSF3) was identified as a potential candidate for the slow fiber specific regulation of ISCU splicing since this factor was expressed at higher levels in the soleus compared to the gastrocnemius and quadriceps. We identified an interaction between SRSF3 and the ISCU transcript, and by overexpressing SRSF3 in human myoblasts we observed increased levels of incorrectly spliced ISCU, while knockdown of SRSF3 resulted in decreased levels. We therefore suggest that SRSF3 may participate in the regulation of the incorrect splicing of mutant ISCU and may, at least partially, explain the muscle-specific symptoms of HML. PMID:27783661

  18. Muscle and Liver Carbohydrates: Response to Military Task Performance by Women and Men

    DTIC Science & Technology

    2001-10-01

    the muscles of the lower leg, while the male population acclimatized to the exercise protocol and relied less on the hamstrings . 3) Over the course of...61: 165-172, 1986. JAP-00394-2002 17 10. Doyle, J.A., W.M. Sherman, and R.L. Strauss. Effects of eccentric and concentric exercise on muscle glycogen...data analysis and found that, unlike men, women work their lower legs harder during the latter stages of exercise than during the first hour. We have

  19. Enhancement of hypoxic liver damage by ethanol. Involvement of xanthine oxidase and the role of glycolysis.

    PubMed

    Younes, M; Strubelt, O

    1987-09-15

    Using isolated hemoglobin-free perfused rat livers we investigated the hepatotoxic effects of hypoxia, ethanol or the combination of both. Hypoxia only (90 min) led to a weak toxicity as evidenced by the efflux of the enzymes glutamate-pyruvate-transaminase (GPT) and sorbitol dehydrogenase (SDH). This toxic effect was slightly higher in livers treated with ethanol (3 g/l) under normoxic conditions. Ethanol added under hypoxic conditions, however, showed a strong hepatotoxic effect. Under hypoxic conditions, lactate + pyruvate production was increased fivefold over control, indicating that glycolysis was more effectively undergone as main source of energy. Addition of ethanol suppressed this effect, indicating that ethanol inhibited glycolysis. These results indicate that ethanol potentiates hypoxic liver damage by inhibiting the main metabolic pathway yielding ATP under low oxygen tension resulting in a severe energy deficit. Allopurinol (100 mg/l) inhibited the toxic effects seen with ethanol + hypoxia. Also, the inhibitory action of ethanol on glycolysis was antagonized. Our results are consistent with the following model: hypoxia converts NAD-dependent xanthine dehydrogenase (XD) into the oxygen-dependent xanthine oxidase (XO). Due to hypoxia and ethanol, purine metabolites and acetaldehyde accumulate and are metabolized via XO. This process leads to the production of oxygen radicals which most probably mediate both the inhibition of glycolysis and the direct toxic effects towards liver cells.

  20. Tc-99m colloid lung uptake in a rare case of toxoplasmosis with liver involvement

    SciTech Connect

    Garty, I.; Tal, I.; Kaynan, A.

    1984-06-01

    Intensive lung accumulation of colloid (Tc-99m phytate) was demonstrated in a child suffering from acquired toxoplasmosis with a rare manifestation of severe liver damage. The possible mechanism and clinical importance of colloid lung concentration in this case is briefly discussed, including a review of the literature on this subject.

  1. Involvement of cyclooxygenase-2 in the potentiation of allyl alcohol-induced liver injury by bacterial lipopolysaccharide.

    PubMed

    Ganey, P E; Barton, Y W; Kinser, S; Sneed, R A; Barton, C C; Roth, R A

    2001-07-15

    Bacterial endotoxin (lipopolysaccharide; LPS) augments the hepatotoxicity of a number of xenobiotics including allyl alcohol. The mechanism for this effect is known to involve the inflammatory response elicited by LPS. Upregulation of cyclooxygenase-2 (COX-2) and production of eicosanoids are important aspects of inflammation, therefore studies were undertaken to investigate the role of COX-2 in LPS-induced enhancement of liver injury from allyl alcohol. Rats were pretreated (iv) with a noninjurious dose of LPS or sterile saline vehicle and 2 h later were treated (ip) with a noninjurious dose of allyl alcohol or saline vehicle. COX-2 mRNA was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and liver injury was assessed from activities in serum of alanine and aspartate aminotransferases (ALT and AST, respectively) and from histology. Liver injury was observed only in rats cotreated with LPS and allyl alcohol. Serum ALT activity was increased by 4 h after administration of LPS and continued to increase through 8 h. COX-2 mRNA was detectable at low levels in livers from rats receiving only the vehicles at any time up to 8 h. Expression of COX-2 mRNA was increased by 30 min after administration of LPS and remained elevated through 6 h. Allyl alcohol treatment alone caused an increase in COX-2 mRNA at 4 h (2 h after allyl alcohol) that lasted less than 2 h. In livers from rats cotreated with LPS and allyl alcohol, levels of COX-2 mRNA were greater than levels seen with either LPS or allyl alcohol alone. The increased expression of COX-2 mRNA was accompanied by an increase in the concentration of prostaglandin (PG) D(2) in plasma. Plasma PGD(2) concentration was increased to a greater extent in rats treated with LPS plus allyl alcohol compared to allyl alcohol or LPS alone. Pretreatment with the COX-2 selective inhibitor, NS-398, abolished the increase in plasma PGD(2) and reduced the increase in ALT and AST activities observed in

  2. Identification of master genes involved in liver key functions through transcriptomics and epigenomics of methyl donor deficiency in rat: relevance to nonalcoholic liver disease.

    PubMed

    Chen, Gaili; Broséus, Julien; Hergalant, Sébastien; Donnart, Audrey; Chevalier, Catherine; Bolaños-Jiménez, Francisco; Guéant, Jean-Louis; Houlgatte, Rémi

    2015-02-01

    Our study aims to investigate molecular events associated to methyl donor deficiency (MDD) by analyzing the transcriptome and the methylome of MDD rats in liver. Twenty-one-day-old rats born to mothers fed either with a standard diet or a MDD diet during gestation and lactation were compared. From a total of 44 000 probes for 26 456 genes, we found two gene clusters in MDD rats whose expression levels had significant differences compared with controls: 3269 overexpressed (p < 0.0009) and 2841 underexpressed (p < 0.0004) genes. Modifications of DNA methylation were found in the promoter regions of 1032 genes out of 14 981 genes. Ontological analyses revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, ER stress, and mitochondrial function. Putative master genes exhibiting changes in both gene expression and DNA methylation are limited to 266 genes and are mainly involved in the renin-angiotensin system (n = 3), mitochondrion metabolism (n = 18), and phospholipid homeostasis (n = 3). Most of these master genes participate in nonalcoholic fatty liver disease. The adverse effects of MDD on the metabolic process indicate the beneficial impact of folate and vitamin B12, especially during the perinatal period. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation

    PubMed Central

    Bohne, Felix; Martínez-Llordella, Marc; Lozano, Juan-José; Miquel, Rosa; Benítez, Carlos; Londoño, María-Carlota; Manzia, Tommaso-María; Angelico, Roberta; Swinkels, Dorine W.; Tjalsma, Harold; López, Marta; Abraldes, Juan G.; Bonaccorsi-Riani, Eliano; Jaeckel, Elmar; Taubert, Richard; Pirenne, Jacques; Rimola, Antoni; Tisone, Giuseppe; Sánchez-Fueyo, Alberto

    2011-01-01

    Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying the allograft. This can cause severe side effects and increased recipient morbidity and mortality. Complete cessation of immunosuppressive drugs has been successfully accomplished in selected transplant recipients, providing proof of principle that operational allograft tolerance is attainable in clinical transplantation. The intra-graft molecular pathways associated with successful drug withdrawal, however, are not well defined. In this study, we analyzed sequential blood and liver tissue samples collected from liver transplant recipients enrolled in a prospective multicenter immunosuppressive drug withdrawal clinical trial. Before initiation of drug withdrawal, operationally tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis. Furthermore, as compared with non-tolerant recipients, operationally tolerant patients exhibited higher serum levels of hepcidin and ferritin and increased hepatocyte iron deposition. Finally, liver tissue gene expression measurements accurately predicted the outcome of immunosuppressive withdrawal in an independent set of patients. These results point to a critical role for iron metabolism in the regulation of intra-graft alloimmune responses in humans and provide a set of biomarkers to conduct drug-weaning trials in liver transplantation. PMID:22156196

  4. [Myositis ossificans of the pterygoid and temporal muscles with metachronous contralateral involvement].

    PubMed

    Salgarelli, A; Magnato, R; Carminati, R; Barbaglio, A; Nocini, P F

    1997-05-01

    After reviewing the literature, the authors report a case of myositis ossificans of the right pterygoid and temporalis muscles in a patient undergoing surgery to remove the left medial pterygoid muscle owing to the same pathology. The metachronous localisation in contralateral masticatory muscles compared to the primary site leads the authors to emphasize the post-traumatic and iatrogenic etiology of this rare pathology. In the light of their experience, they underline the importance of a precise diagnosis and surgical exeresis, followed by cautious rehabilitation with the least trauma, if necessary backed by appropriate medical treatment.

  5. Enforced expression of protein kinase C in skeletal muscle causes physical inactivity, fatty liver and insulin resistance in the brain.

    PubMed

    Hennige, Anita M; Heni, Martin; Machann, Jürgen; Staiger, Harald; Sartorius, Tina; Hoene, Miriam; Lehmann, Rainer; Weigert, Cora; Peter, Andreas; Bornemann, Antje; Kroeber, Stefan; Pujol, Anna; Franckhauser, Sylvie; Bosch, Fatima; Schick, Fritz; Lammers, Reiner; Häring, Hans-Ulrich

    2010-04-01

    Among the multitude of dysregulated signalling mechanisms that comprise insulin resistance in divergent organs, the primary events in the development of type 2 diabetes are not well established. As protein kinase C (PKC) activation is consistently present in skeletal muscle of obese and insulin resistant subjects, we generated a transgenic mouse model that overexpresses constitutively active PKC-beta(2) in skeletal muscle to test whether activation of PKC is sufficient to cause an aversive whole-body phenotype. Upon this genetic modification, increased serine phosphorylation in Irs1 was observed and followed by impaired (3)H-deoxy-glucose uptake and muscle glycogen content, and transgenic mice exhibited insulin and glucose intolerance as they age. Muscle histochemistry revealed an increase in lipid deposition (intramyocellular lipids), and transgenic mice displayed impaired expression of transcriptional regulators of genes involved in fatty acid oxidation (peroxisome proliferator-activated receptor-gamma, PGC-1beta, acyl-CoA oxidase) and lipolysis (hormone-sensitive lipase). In this regard, muscle of transgenic mice exhibited a reduced capacity to oxidize palmitate and contained less mitochondria as determined by citrate synthase activity. Moreover, the phenotype included a profound decrease in the daily running distance, intra-abdominal and hepatic fat accumulation and impaired insulin action in the brain. Together, our data suggest that activation of a classical PKC in skeletal muscle as present in the pre-diabetic state is sufficient to cause disturbances in whole-body glucose and lipid metabolism followed by profound alterations in oxidative capacity, ectopic fat deposition and physical activity.

  6. Enforced expression of protein kinase C in skeletal muscle causes physical inactivity, fatty liver and insulin resistance in the brain

    PubMed Central

    Hennige, Anita M; Heni, Martin; Machann, Jürgen; Staiger, Harald; Sartorius, Tina; Hoene, Miriam; Lehmann, Rainer; Weigert, Cora; Peter, Andreas; Bornemann, Antje; Kroeber, Stefan; Pujol, Anna; Franckhauser, Sylvie; Bosch, Fatima; Schick, Fritz; Lammers, Reiner; Häring, Hans-Ulrich

    2010-01-01

    Abstract Among the multitude of dysregulated signalling mechanisms that comprise insulin resistance in divergent organs, the primary events in the development of type 2 diabetes are not well established. As protein kinase C (PKC) activation is consistently present in skeletal muscle of obese and insulin resistant subjects, we generated a transgenic mouse model that overexpresses constitutively active PKC-β2 in skeletal muscle to test whether activation of PKC is sufficient to cause an aversive whole-body phenotype. Upon this genetic modification, increased serine phosphorylation in Irs1 was observed and followed by impaired 3H-deoxy-glucose uptake and muscle glycogen content, and transgenic mice exhibited insulin and glucose intolerance as they age. Muscle histochemistry revealed an increase in lipid deposition (intramyocellular lipids), and transgenic mice displayed impaired expression of transcriptional regulators of genes involved in fatty acid oxidation (peroxisome proliferator-activated receptor-γ, PGC-1β, acyl-CoA oxidase) and lipolysis (hormone-sensitive lipase). In this regard, muscle of transgenic mice exhibited a reduced capacity to oxidize palmitate and contained less mitochondria as determined by citrate synthase activity. Moreover, the phenotype included a profound decrease in the daily running distance, intra-abdominal and hepatic fat accumulation and impaired insulin action in the brain. Together, our data suggest that activation of a classical PKC in skeletal muscle as present in the pre-diabetic state is sufficient to cause disturbances in whole-body glucose and lipid metabolism followed by profound alterations in oxidative capacity, ectopic fat deposition and physical activity. PMID:20569275

  7. Determinants of muscle metaboreflex and involvement of baroreflex in boys and young men.

    PubMed

    Dipla, Konstantina; Papadopoulos, Stavros; Zafeiridis, Andreas; Kyparos, Antonios; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2013-04-01

    This study aimed to assess the arterial pressure (AP) determinants during the muscle metaboreflex in boys and men and to investigate the contribution of baroreflex and sympathovagal function to the metaboreflex-induced responses. Fourteen pre-adolescent boys and 13 men performed a protocol involving: baseline, isometric handgrip exercise, circulatory occlusion, and recovery. The same protocol was repeated without occlusion. During baseline, boys had lower beat-to-beat AP, higher heart rate (HR), and lower low/high frequency HR variability. During exercise, a parasympathetic withdrawal was evident in both groups. In adults, HR was the key contributor to the pressure response, with no changes in stroke volume, whereas in boys, the lower HR increase was counterbalanced by an increase in stroke volume, resulting in similar relative increases in AP in both groups. In recovery, boys exhibited a faster rate of HR-decay, rapid vagal reactivation, and greater decrease in TPR than men. An overshoot in baroreceptor sensitivity was observed in men. The isolated metaboreflex resulted in a similar AP elevation in both age groups (by ~15 mmHg), and attenuated spontaneous baroreceptor sensitivity. However, during the metaboreflex, pre-adolescent males exhibited a lower increase in peripheral resistance and a greater bradycardic response than adults, and a fast restoration of vagal activity to non-occlusion levels. During metaboreflex, boys were capable of eliciting a pressure response similar to the one elicited by men; however, the interplay of the mechanisms underlying the rise in AP differed between the two groups with the vagal contribution being greater in the younger participants.

  8. Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement

    PubMed Central

    Alrashdan, Yazan A.; Alkhouri, Hatem; Chen, Emily; Lalor, Daniel J.; Poniris, Maree; Henness, Sheridan; Brightling, Christopher E.; Burgess, Janette K.; Armour, Carol L.; Ammit, Alaina J.

    2012-01-01

    CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma. PMID:22387292

  9. Vascular smooth muscle cell differentiation to an osteogenic phenotype involves matrix metalloproteinase-2 modulation by homocysteine.

    PubMed

    Liu, Tingjiao; Lin, Jinghan; Ju, Ting; Chu, Lei; Zhang, Liming

    2015-08-01

    Arterial calcification is common in vascular diseases and involves conversion of vascular smooth muscle cells (VSMCs) to an osteoblast phenotype. Clinical studies suggest that the development of atherosclerosis can be promoted by homocysteine (HCY), but the mechanisms remain unclear. Here, we determined whether increases in HCY levels lead to an increase in VSMC calcification and differentiation, and examined the role of an extracellular matrix remodeler, matrix metalloproteinase-2 (MMP-2). Rat VSMCs were exposed to calcification medium in the absence or presence of HCY (10, 100 or 200 μmol/L) or an MMP-2 inhibitor (10(-6) or 10(-5) mol/L). MTT assays were performed to determine the cytotoxicity of the MMP-2 inhibitor in calcification medium containing 200 μmol/L HCY. Calcification was assessed by measurements of calcium deposition and alkaline phosphatase (ALP) activity as well as von Kossa staining. Expression of osteocalcin, bone morphogenetic protein (BMP)-2, and osteopontin, and MMP-2 was determined by immunoblotting. Calcification medium induced osteogenic differentiation of VSMCs. HCY promoted calcification, increased osteocalcin and BMP-2 expression, and decreased expression of osteopontin. MMP-2 expression was increased by HCY in a dose-dependent manner in VSMCs exposed to both control and calcification medium. The MMP-2 inhibitor decreased the calcium content and ALP activity, and attenuated the osteoblastic phenotype of VSMCs. Vascular calcification and osteogenic differentiation of VSMCs were positively regulated by HCY through increased/restored MMP-2 expression, increased expression of calcification proteins, and decreased anti-calcification protein levels. In summary, MMP-2 inhibition may be a protective strategy against VSMC calcification.

  10. Involvement of catecholaminergic neurons in motor innervation of striated muscle in the mouse esophagus.

    PubMed

    van der Keylen, Piet; Garreis, Fabian; Steigleder, Ruth; Sommer, Daniel; Neuhuber, Winfried L; Wörl, Jürgen

    2016-05-01

    Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may

  11. MRI displays involvement of the temporalis muscle and the deep temporal artery in patients with giant cell arteritis.

    PubMed

    Veldhoen, Simon; Klink, Thorsten; Geiger, Julia; Vaith, Peter; Glaser, Cornelia; Ness, Thomas; Duwendag, Dirk; Both, Marcus; Bley, Thorsten A

    2014-11-01

    To assess deep temporal artery and temporalis muscle involvement in patients with giant cell arteritis (GCA). Ninety-nine patients who received magnetic resonance imaging (MRI) and superficial temporal artery biopsy (TAB) were included in this study. Patients with positive TAB (n = 61) were defined as GCA patients, those with negative TAB (n = 38) as the GCA-negative reference group. Contrast-enhanced T1w-images were acquired utilizing 1.5 T and 3 T MRI. Two radiologists assessed the images. Mural contrast-hyperenhancement and wall thickening of the deep temporal artery and hyperenhancement of the muscle were defined as inflammation. MRI results were correlated with jaw claudication in 70 patients. The two observers found temporalis muscle involvement in 19.7 % (n = 12) and 21.3 % (n = 13) of GCA patients. It occurred bilaterally in 100 %. Specificities were 92/97 % and sensitivities were 20/21 %. Deep temporal artery involvement was found in 34.4 % (n = 21) and 49.2 % (n = 30) and occurred bilaterally in 80/90.5 %. Specificities were 84/95 % and sensitivities were 34/49 %. Both structures were affected simultaneously in 18/21.3 %. Jaw claudication correlated moderately with inflammation of the temporalis muscle (r = 0.31; p < 0.05) and the deep temporal artery (r = 0.38; p = 0.01). MRI visualizes changes in the temporalis muscle and the deep temporal artery in GCA. Moderate correlation of clinical symptoms with MRI results was observed. • Approximately 20 % of GCA patients presented with temporalis muscle inflammation. • A total of 34-49 % of GCA patients presented with vasculitis of the deep temporal artery. • In approximately 20 % of GCA patients, both structures were simultaneously involved. • Involvement of both structures correlated moderately with presence of jaw claudication. • MRI is a suitable tool for the assessment of vasculitis and muscle inflammation.

  12. Moderate nutrient restriction influences transcript abundance of genes impacting production efficiencies of beef cattle in fetal liver, muscle, and cerebrum by d 50 of gestation

    USDA-ARS?s Scientific Manuscript database

    We hypothesized that a moderate maternal nutrient restriction during the first 50 d of gestation in beef heifers would affect transcript abundance of genes impacting production efficiency phenotypes in fetal liver, muscle, and cerebrum. Fourteen Angus-cross heifers were estrus synchronized and assig...

  13. Age dependent accumulation patterns of advanced glycation end product receptor (RAGE) ligands and binding intensities between RAGE and its ligands differ in the liver, kidney, and skeletal muscle.

    PubMed

    Son, Myeongjoo; Chung, Wook-Jin; Oh, Seyeon; Ahn, Hyosang; Choi, Chang Hu; Hong, Suntaek; Park, Kook Yang; Son, Kuk Hui; Byun, Kyunghee

    2017-01-01

    Much evidence indicates receptor for advanced glycation end products (RAGE) related inflammation play essential roles during aging. However, the majority of studies have focused on advanced glycation end products (AGEs) and not on other RAGE ligands. In the present study, the authors evaluated whether the accumulation of RAGE ligands and binding intensities between RAGE and its ligands differ in kidney, liver, and skeletal muscle during aging. In C57BL/6 N mice aged 12 weeks, 12 months, and 22 months, ligands accumulation, binding intensities between RAGE and its ligands, activated macrophage infiltration, M1/M2 macrophage expression, glyoxalase-1expression, and signal pathways related to inflammation were evaluated. The RAGE ligands age-associated accumulation patterns were found to be organ dependent. Binding intensities between RAGE and its ligands in kidney and liver increased with age, but those in skeletal muscle were unchanged. Infiltration of activated macrophages in kidney and liver increased with age, but infiltration in the skeletal muscle was unchanged. M1 expression increased and M2 and glyoxalase-1 expression decreased with age in kidney and liver, but their expressions in skeletal muscle were not changed. These findings indicate patterns of RAGE ligands accumulation, RAGE/ligands binding intensities, or inflammation markers changes during aging are organs dependent.

  14. Mercury and selenium concentrations in skeletal muscle, liver, and regions of the heart and kidney in bearded seals from Alaska, USA.

    PubMed

    Correa, Lucero; Castellini, J Margaret; Quakenbush, Lori T; O'Hara, Todd M

    2015-10-01

    Mean concentrations of total mercury ([THg]) and selenium ([TSe]) (mass and molar-based) were determined for 5 regions of the heart and 2 regions of the kidney of bearded seals (Erignathus barbatus) harvested in Alaska, USA, in 2010 and 2011. Mean [THg] and [TSe] of bearded seal liver and skeletal muscle tissues were used for intertissular comparison. The Se:Hg molar ratios were used to investigate elemental associations and potential antioxidant protection against Hg toxicosis. Age was an important factor in [THg] and Se:Hg molar ratios in heart and kidney. Small but statistically significant differences in mean [THg] occurred among some of the 5 heart regions (p < 0.05). Mean [THg] was highest in liver, 3.057 µg/g, and lowest in heart left ventricle, 0.017 µg/g. Mean [THg] ranked: liver > kidney cortex > kidney medulla > skeletal muscle > heart left ventricle (p < 0.001). Mean [TSe] was highest in liver, 3.848 µg/g, and lowest in heart left ventricle, 0.632 µg/g. Mean [TSe] ranked: liver > kidney cortex > kidney medulla > skeletal muscle > heart left ventricle (p < 0.001). The Se:Hg molar ratios were significantly greater than 1.0 in all tissues (p < 0.001) and represented baselines for normal [TSe] under relatively low [THg]. Mean Se:Hg molar ratios ranked: heart left ventricle > kidney medulla > kidney cortex (p < 0.001).

  15. Muscle and Liver Carbohydrates: Response to Military Task Performance by Women and Men

    DTIC Science & Technology

    2000-10-01

    effect of three different nutritional supplements upon muscle glycogen recovery. Since altering our protocol, we have made significant progress in...consecutive days of exercise) of the project (Hypothesis IV). D. Initiating an appropriate exercise protocol to study the effects of nutritional supplementation... nutritional supplementation following severe glycogen depleting exercise. 9) Initiate this final portion of the project and obtain data from a significant

  16. Impact of dietary fatty acids on muscle composition, liver lipids, milt composition and sperm performance in European eel.

    PubMed

    Butts, Ian Anthony Ernest; Baeza, Rosa; Støttrup, Josianne Gatt; Krüger-Johnsen, Maria; Jacobsen, Charlotte; Pérez, Luz; Asturiano, Juan F; Tomkiewicz, Jonna

    2015-05-01

    In order for European eel aquaculture to be sustainable, the life cycle should be completed in captivity. Development of broodstock diets may improve the species' reproductive success in captivity, through the production of high-quality gametes. Here, our aim was to evaluate the influence of dietary regime on muscle composition, and liver lipids prior to induced maturation, and the resulting sperm composition and performance. To accomplish this fish were reared on three "enhanced" diets and one commercial diet, each with different levels of fatty acids, arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Neutral lipids from the muscle and liver incorporated the majority of the fatty acid profile, while phospholipids incorporated only certain fatty acids. Diet had an effect on the majority of sperm fatty acids, on the total volume of extractable milt, and on the percentage of motile sperm. Here, our results suggest that the total volume of extractable milt is a DHA-dependent process, as we found the diets with the highest DHA levels induced the most milt while the diet with the lowest DHA level induced the least amount of milt. The diet with the highest level of ARA induced medium milt volumes but had the highest sperm motility. EPA also seems important for sperm quality parameters since diets with higher EPA percentages had a higher volume of milt and higher sperm motility. In conclusion, dietary fatty acids had an influence on fatty acids in the tissues of male eel and this impacted sperm performance. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    SciTech Connect

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  18. Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophy.

    PubMed

    Lamon, Séverine; Wallace, Marita A; Léger, Bertrand; Russell, Aaron P

    2009-04-15

    Skeletal muscle atrophy is a severe consequence of ageing, neurological disorders and chronic disease. Identifying the intracellular signalling pathways controlling changes in skeletal muscle size and function is vital for the future development of potential therapeutic interventions. Striated activator of Rho signalling (STARS), an actin-binding protein, has been implicated in rodent cardiac hypertrophy; however its role in human skeletal muscle has not been determined. This study aimed to establish if STARS, as well as its downstream signalling targets, RhoA, myocardin-related transcription factors A and B (MRTF-A/B) and serum response factor (SRF), were increased and decreased respectively, in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. The mRNA levels of the SRF target genes involved in muscle structure, function and growth, such as alpha-actin, myosin heavy chain IIa (MHCIIa) and insulin-like growth factor-1 (IGF-1), were also measured. Following resistance training, STARS, MRTF-A, MRTF-B, SRF, alpha-actin, MHCIIa and IGF-1 mRNA, as well as RhoA and nuclear SRF protein levels were all significantly increased by between 1.25- and 3.6-fold. Following the de-training period all measured targets, except for RhoA, which remained elevated, returned to base-line. Our results show that the STARS signalling pathway is responsive to changes in skeletal muscle loading and appears to play a role in both human skeletal muscle hypertrophy and atrophy.

  19. Echinococcosis involving the liver, retrovesical and seminal vesicle presented with syncope.

    PubMed

    Ozer, Tulay; Gundogdu, Sadi; Ozer, Yetkin; Mahmutyazicioglu, Kamran; Savranlar, Ahmet; Ozdemir, Huseyin

    2004-10-01

    Hydatid disease of the urogenital system, especially of the retroperitoneum and seminal vesicles, is a very rare condition. We report a case of hydatid disease located in the liver, retrovesical region and seminal vesicle that was diagnosed incidentally while investigating the etiology of syncope. Transabdominal and transrectal ultrasonography revealed hypoecoic multicystic masses which had thin septations and walls in the liver, retrovesical region and seminal vesicle. Abdominal computed tomography examination showed multicystic low attenuation masses in the same region. Pelvic magnetic resonance image findings revealed multiple cystic masses in the retrovesical region and the right seminal vesicle. In conclusion, the diagnosis of hydatid disease should be kept in mind with patients who have cystic lesions in seminal vesicle and retrovesical region.

  20. Heat stroke and multi-organ failure with liver involvement in an asylum-seeking refugee.

    PubMed

    Deutsch, Melanie; Koskinas, John; Emmanuel, Theodoros; Kountouras, Dimitris; Hadziyannis, Stephanos

    2006-10-01

    Heat stroke is the result of exposure to high environmental temperature and strenuous exercise representing a medical emergency characterized by an elevated core body temperature and central nervous system disorders. Slightly elevated liver enzymes, lacking clinical significance, seem to be frequent in heat stroke, whereas severe, clinically relevant, hepatocellular injury has been observed in only a minority of cases. In the present report we describe the case of an otherwise healthy young asylum-seeking refugee from East Timor, who developed severe heat stroke during his transportation to Greece in a closed container on a ship under unusually high temperatures. He was admitted to the hospital with severe multi-organ failure. After a short period of initial improvement, he developed severe hepatocellular injury and hepatic encephalopathy. Other causes of liver damage were excluded. The patient completely recovered.

  1. Effect of dietary nonstructural carbohydrate content on activation of 5'-adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and digital laminae of lean and obese ponies.

    PubMed

    Burns, T A; Watts, M R; Weber, P S; McCutcheon, L J; Geor, R J; Belknap, J K

    2014-01-01

    In EMS-associated laminitis, laminar failure may occur in response to energy failure related to insulin resistance (IR) or to the effect of hyperinsulinemia on laminar tissue. 5'-Adenosine-monophosphate-activated protein kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR. To characterize tissue AMPK regulation in ponies subjected to a dietary carbohydrate (CHO) challenge. Twenty-two mixed-breed ponies. Immunohistochemistry and immunoblotting for total AMPK and phospho(P)-AMPK and RT-qPCR for AMPK-responsive genes were performed on laminar, liver, and skeletal muscle samples collected after a 7-day feeding protocol in which ponies stratified on body condition score (BCS; obese or lean) were fed either a low-CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or a high-CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean). 5'-Adenosine-monophosphate-activated protein kinase was immunolocalized to laminar keratinocytes, dermal constituents, and hepatocytes. A high-CHO diet resulted in significantly decreased laminar [P-AMPK] in lean ponies (P = .03), but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean, P = .84; obese, P = .13) [P-AMPK]. An inverse correlation existed between [blood glucose] and laminar [P-AMPK] in obese ponies on a high-CHO diet. Laminar tissue exhibited a normal response to a high-CHO diet (decreased [P-AMPK]), whereas this response was not observed in liver and skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese (skeletal muscle, P = .43; liver, P = .13) ponies. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  2. Involvement of CYP2D6 in oxidative metabolism of cinnarizine and flunarizine in human liver microsomes.

    PubMed

    Narimatsu, S; Kariya, S; Isozaki, S; Ohmori, S; Kitada, M; Hosokawa, S; Masubuchi, Y; Suzuki, T

    1993-06-30

    Oxidative metabolism of cinnarizine (CZ) and its fluorine derivative flunarizine (FZ), both of which are selective calcium entry blockers, was examined in human liver microsomes. The ring-hydroxylations and the N-desalkylations constituted primary metabolic pathways in microsomal metabolism of CZ and FZ. Among these pathways, the ring-hydroxylase (p-hydroxylation) activities at the cinnamyl moiety of both drugs were highly correlated with debrisoquine 4-hydroxylase activity and CYP2D6 content. Quinidine, a selective inhibitor of CYP2D6, suppressed the ring-hydroxylase activities of CZ and FZ. These results suggest that CYP2D6 is involved in the ring-hydroxylation of the cinnamyl moiety of both CZ and FZ in human liver microsomes.

  3. Endocytic collagen degradation: a novel mechanism involved in protection against liver fibrosis.

    PubMed

    Madsen, Daniel H; Jürgensen, Henrik J; Ingvarsen, Signe; Melander, Maria C; Vainer, Ben; Egerod, Kristoffer L; Hald, Andreas; Rønø, Birgitte; Madsen, Charlotte A; Bugge, Thomas H; Engelholm, Lars H; Behrendt, Niels

    2012-05-01

    Fibrosis of the liver and its end-stage, cirrhosis, represent major health problems worldwide. In these fibrotic conditions, activated fibroblasts and hepatic stellate cells display a net deposition of collagen. This collagen deposition is a major factor leading to liver dysfunction, thus making it crucially important to understand both the collagen synthesis and turnover mechanisms in this condition. Here we show that the endocytic collagen receptor, uPARAP/Endo180, is a major determinant in governing the balance between collagen deposition and degradation. Cirrhotic human livers displayed a marked up-regulation of uPARAP/Endo180 in activated fibroblasts and hepatic stellate cells located close to the collagen deposits. In a hepatic stellate cell line, uPARAP/Endo180 was shown to be active in, and required for, the uptake and intracellular degradation of collagen. To evaluate the functional importance of this collagen receptor in vivo, liver fibrosis was induced in uPARAP/Endo180-deficient mice and littermate wild-type mice by chronic CCl(4) administration. A strong up-regulation of uPARAP/Endo180 was observed in wild-type mice, and a quantitative comparison of collagen deposits in the two groups of mice clearly revealed a fibrosis protective role of uPARAP/Endo180. This effect appeared to directly reflect the activity of the collagen receptor, since no compensatory events were noted when comparing the mRNA expression profiles of the two groups of mice in an array system focused on matrix-degrading components. This function of uPARAP/Endo180 defines a novel role of intracellular collagen turnover in fibrosis protection.

  4. Muscle-specific deletion of signal transducer and activator of transcription 5 augments lipid accumulation in skeletal muscle and liver of mice in response to high-fat diet.

    PubMed

    Baik, Myunggi; Lee, Mi Sun; Kang, Hyeok Joong; Park, Seung Ju; Piao, Min Yu; Nguyen, Trang Hoa; Hennighausen, Lothar

    2017-03-01

    Growth hormone (GH) controls liver metabolism through the transcription factor signal transducer and activator of transcription 5 (STAT5). However, it remains to be fully understood to what extent other GH/STAT5 target tissues contribute to lipid and glucose metabolism. This question was now addressed in muscle-specific STAT5 knockout (STAT5 MKO) mice model. Changes in lipid and glucose metabolism were investigated at physiological and molecular levels in muscle and liver tissues of STAT5 MKO mice under normal diet or high-fat diet (HFD) conditions. STAT5 MKO mice exhibited an increased intramyocellular lipid (IMCL) accumulation in the quadriceps in HFD group. Decreased lipolytic hormone-sensitive lipase transcript levels may contribute to the increased IMCL accumulation in STAT5 MKO mice. STAT5 MKO induced hepatic lipid accumulation without deregulated STAT5 signaling. The upregulation of lipoprotein lipase and Cd36 mRNA levels, an increased trend of very low-density lipoprotein receptor mRNA levels, and elevated circulating concentrations of free fatty acid, triglyceride, and total cholesterol support the increase in hepatic lipid accumulation. STAT5 MKO in conjunction with a HFD deregulated both lipid and glucose metabolism in skeletal muscle, and this deregulation induced hepatic fat accumulation via increased circulating glucose, FFA, and TG concentrations. Our study emphasizes that muscle-specific STAT5 signaling is important for balancing lipid and glucose metabolism in peripheral tissues, including muscle and liver and that the deregulation of local STAT5 signaling augments HFD-induced lipid accumulation in both muscle and liver.

  5. Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists.

    PubMed

    Gonzalez, Javier T; Fuchs, Cas J; Smith, Fiona E; Thelwall, Pete E; Taylor, Roy; Stevenson, Emma J; Trenell, Michael I; Cermak, Naomi M; van Loon, Luc J C

    2015-12-15

    The purpose of this study was to define the effect of glucose ingestion compared with sucrose ingestion on liver and muscle glycogen depletion during prolonged endurance-type exercise. Fourteen cyclists completed two 3-h bouts of cycling at 50% of peak power output while ingesting either glucose or sucrose at a rate of 1.7 g/min (102 g/h). Four cyclists performed an additional third test for reference in which only water was consumed. We employed (13)C magnetic resonance spectroscopy to determine liver and muscle glycogen concentrations before and after exercise. Expired breath was sampled during exercise to estimate whole body substrate use. After glucose and sucrose ingestion, liver glycogen levels did not show a significant decline after exercise (from 325 ± 168 to 345 ± 205 and 321 ± 177 to 348 ± 170 mmol/l, respectively; P > 0.05), with no differences between treatments. Muscle glycogen concentrations declined (from 101 ± 49 to 60 ± 34 and 114 ± 48 to 67 ± 34 mmol/l, respectively; P < 0.05), with no differences between treatments. Whole body carbohydrate utilization was greater with sucrose (2.03 ± 0.43 g/min) vs. glucose (1.66 ± 0.36 g/min; P < 0.05) ingestion. Both liver (from 454 ± 33 to 283 ± 82 mmol/l; P < 0.05) and muscle (from 111 ± 46 to 67 ± 31 mmol/l; P < 0.01) glycogen concentrations declined during exercise when only water was ingested. Both glucose and sucrose ingestion prevent liver glycogen depletion during prolonged endurance-type exercise. Sucrose ingestion does not preserve liver glycogen concentrations more than glucose ingestion. However, sucrose ingestion does increase whole body carbohydrate utilization compared with glucose ingestion. This trial was registered at https://www.clinicaltrials.gov as NCT02110836. Copyright © 2015 the American Physiological Society.

  6. Differences in tissue oxygenation and changes in total hemoglobin signal strength in the brain, liver, and lower-limb muscle during hemodialysis.

    PubMed

    Ookawara, Susumu; Ito, Kiyonori; Ueda, Yuichiro; Miyazawa, Haruhisa; Hayasaka, Hideyuki; Kofuji, Masaya; Uchida, Takayuki; Ishii, Hiroki; Shindo, Mitsutoshi; Kitano, Taisuke; Aomatsu, Akinori; Hirai, Keiji; Kaku, Yoshio; Hoshino, Taro; Tabei, Kaoru; Morishita, Yoshiyuki

    2017-08-07

    Near-infrared spectroscopy has been used to measure regional saturation of oxygen (rSO2) based on the total hemoglobin (t-Hb) signal strength. To date, few studies have investigated the changes of systemic oxygenation and t-Hb signal strength during hemodialysis (HD). This study aimed to (1) monitor rSO2 and t-Hb signal strength in the brain, liver, and lower-limb muscle during HD and (2) clarify the differences in rSO2 and t-Hb signal strength in each compartment. Fifty-three patients receiving 4-h HD were included and divided into three groups according to the compartments in which tissue oxygenation was measured as follows: brain (n = 44), liver (n = 42), and lower-limb muscle (n = 40). The rSO2 and t-Hb signal strength was monitored using an INVOS 5100c (Covidien Japan, Tokyo, Japan). The rSO2 levels were significantly lower in the brain than in the liver from HD initiation to the end (HD initiation: rSO2 in the brain and liver, 46.5 ± 1.3 and 52.4 ± 1.7%, respectively, p = 0.031). Furthermore, compared to the t-Hb signal strength ratio [value at t (min) during HD/initial value before HD] in the brain during HD, there were significant increases in the liver and lower-limb muscle, respectively. In conclusion, deterioration of cerebral oxygenation was remarkable compared to the hepatic oxygenation in HD patients. Our results, which revealed significant differences among the t-Hb signal strength ratios in the brain, liver, and lower-limb muscle during HD, might reflect the non-uniform body-fluid reduction within systemic tissues induced by ultrafiltration.

  7. Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury.

    PubMed

    Dai, Jie; Liu, Mingwei; Ai, Qing; Lin, Ling; Wu, Kunwei; Deng, Xinyu; Jing, Yuping; Jia, Mengying; Wan, Jingyuan; Zhang, Li

    2014-06-05

    Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl₂)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl₂-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl₄-induced elevation of hepatic H₂O₂ levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl₄-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. MRI and clinical studies of facial and bulbar muscle involvement in MuSK antibody-associated myasthenia gravis.

    PubMed

    Farrugia, Maria Elena; Robson, Matthew D; Clover, Linda; Anslow, Phil; Newsom-Davis, John; Kennett, Robin; Hilton-Jones, David; Matthews, Paul M; Vincent, Angela

    2006-06-01

    A proportion of patients with myasthenia gravis (MG) without acetylcholine receptor (AChR) antibodies have antibodies to muscle-specific kinase (MuSK). MG with MuSK antibodies (MuSK-MG) is often associated with persistent bulbar involvement, including marked facial weakness and tongue muscle wasting. The extent of muscle wasting in MuSK-MG, and whether it is also found in the few acetylcholine receptor (AChR-MG) patients who have persistent bulbar involvement, is not clear. We studied 12 MuSK-MG patients and recruited 14 AChR-MG patients matched broadly for age, sex ratio, duration of disease and degree of ocular, bulbar and facial weakness. We used coronal and sagittal T1-weighted (T1W) and T2-weighted (T2W) magnetic resonance imaging (MRI) to assess muscle wasting in facial and tongue muscles. Hyperintense signal on T1W MRI and comparison of axial T1W sequences with cUTE sequences were used to assess fibrous/fatty tissue in the tongue. We compared the results with those of four patients with myotonic dystrophy and 12 healthy individuals. We correlated the changes with clinical and treatment histories, and established a new ocular-bulbar-facial-respiratory (OBFR) score. At the time of study, none of the clinical measures, including the OBFR score, differed between the two MG groups. MRI demonstrated thinning of the buccinator, orbicularis oris (O.oris) and orbicularis oculi (O.oculi) muscles in MuSK-MG patients compared with healthy controls, whereas thinning of these muscles was not significant in AChR-MG. Tongue areas with T1W high signal were increased in MuSK-MG patients and the intensity of the signal on axial T1W sequences was greater in MuSK-MG than in controls. To look for possible correlations between imaging and clinical findings, we pooled results from all MG patients. The duration of treatment with prednisolone at >40 mg on alternate days (AD) correlated positively with the percentage of tongue area with high signal (P = 0.006) and negatively with MRI

  9. Heat-shock responsive genes identified and validated in Atlantic cod (Gadus morhua) liver, head kidney and skeletal muscle using genomic techniques

    PubMed Central

    2010-01-01

    Background Daily and seasonal changes in temperature are challenges that fish within aquaculture settings cannot completely avoid, and are known to elicit complex organismal and cellular stress responses. We conducted a large-scale gene discovery and transcript expression study in order to better understand the genes that are potentially involved in the physiological and cellular aspects of stress caused by heat-shock. We used suppression subtractive hybridization (SSH) cDNA library construction and characterization to identify transcripts that were dysregulated by heat-shock in liver, skeletal muscle and head kidney of Atlantic cod. These tissues were selected due to their roles in metabolic regulation, locomotion and growth, and immune function, respectively. Fish were exposed for 3 hours to an 8°C elevation in temperature, and then allowed to recover for 24 hours at the original temperature (i.e. 10°C). Tissue samples obtained before heat-shock (BHS), at the cessation of heat-shock (CS), and 3, 12, and 24 hours after the cessation of heat-shock (ACS), were used for reciprocal SSH library construction and quantitative reverse transcription - polymerase chain reaction (QPCR) analysis of gene expression using samples from a group that was transferred but not heat-shocked (CT) as controls. Results We sequenced and characterized 4394 ESTs (1524 from liver, 1451 from head kidney and 1419 from skeletal muscle) from three "forward subtracted" libraries (enriched for genes up-regulated by heat-shock) and 1586 from the liver "reverse subtracted" library (enriched for genes down-regulated by heat-shock), for a total of 5980 ESTs. Several cDNAs encoding putative chaperones belonging to the heat-shock protein (HSP) family were found in these libraries, and "protein folding" was among the gene ontology (GO) terms with the highest proportion in the libraries. QPCR analysis of HSP90α and HSP70-1 (synonym: HSPA1A) mRNA expression showed significant up-regulation in all three

  10. Stimulatory Effect of Insulin on Glucose Uptake by Muscle Involves the Central Nervous System in Insulin-Sensitive Mice

    PubMed Central

    Coomans, Claudia P.; Biermasz, Nienke R.; Geerling, Janine J.; Guigas, Bruno; Rensen, Patrick C.N.; Havekes, Louis M.; Romijn, Johannes A.

    2011-01-01

    OBJECTIVE Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin–stimulated tissue-specific glucose uptake. RESEARCH DESIGN AND METHODS Tolbutamide, an inhibitor of ATP-sensitive K+ channels (KATP channels), or vehicle was infused into the lateral ventricle in the basal state and during hyperinsulinemic-euglycemic conditions in postabsorptive, chow-fed C57Bl/6J mice and in postabsorptive C57Bl/6J mice with diet-induced obesity. Whole-body glucose uptake was measured by d-[14C]glucose kinetics and tissue-specific glucose uptake by 2-deoxy-d-[3H]glucose uptake. RESULTS During clamp conditions, intracerebroventricular administration of tolbutamide impaired the ability of insulin to inhibit EGP by ∼20%. In addition, intracerebroventricular tolbutamide diminished insulin-stimulated glucose uptake in muscle (by ∼59%) but not in heart or adipose tissue. In contrast, in insulin-resistant mice with diet-induced obesity, intracerebroventricular tolbutamide did not alter the effects of insulin during clamp conditions on EGP or glucose uptake by muscle. CONCLUSIONS Insulin stimulates glucose uptake in muscle in part through effects via KATP channels in the central nervous system, in analogy with the inhibitory effects of insulin on EGP. High-fat diet–induced obesity abolished the central effects of insulin on liver and muscle. These observations stress the role of central insulin resistance in the pathophysiology of diet-induced insulin resistance. PMID:22028182

  11. T-to-R switch of muscle fructose-1,6-bisphosphatase involves fundamental changes of secondary and quaternary structure.

    PubMed

    Barciszewski, Jakub; Wisniewski, Janusz; Kolodziejczyk, Robert; Jaskolski, Mariusz; Rakus, Dariusz; Dzugaj, Andrzej

    2016-04-01

    Fructose-1,6-bisphosphatase (FBPase) catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and is a key enzyme of gluconeogenesis and glyconeogenesis and, more generally, of the control of energy metabolism and glucose homeostasis. Vertebrates, and notably Homo sapiens, express two FBPase isoforms. The liver isozyme is expressed mainly in gluconeogenic organs, where it functions as a regulator of glucose synthesis. The muscle isoform is expressed in all cells, and recent studies have demonstrated that its role goes far beyond the enzymatic function, as it can interact with various nuclear and mitochondrial proteins. Even in its enzymatic function, the muscle enzyme is different from the liver isoform, as it is 100-fold more susceptible to allosteric inhibition by AMP and this effect can be abrogated by complex formation with aldolase. All FBPases are homotetramers composed of two intimate dimers: the upper dimer and the lower dimer. They oscillate between two conformational states: the inactive T form when in complex with AMP, and the active R form. Parenthetically, it is noted that bacterial FBPases behave somewhat differently, and in the absence of allosteric activators exist in a tetramer-dimer equilibrium even at relatively high concentrations. [Hines et al. (2007), J. Biol. Chem. 282, 11696-11704]. The T-to-R transition is correlated with the conformation of the key loop L2, which in the T form becomes `disengaged' and unable to participate in the catalytic mechanism. The T states of both isoforms are very similar, with a small twist of the upper dimer relative to the lower dimer. It is shown that at variance with the well studied R form of the liver enzyme, which is flat, the R form of the muscle enzyme is diametrically different, with a perpendicular orientation of the upper and lower dimers. The crystal structure of the muscle-isozyme R form shows that in this arrangement of the tetramer completely new protein surfaces are exposed

  12. Muscle atrophy as pre-sarcopenia in Japanese patients with chronic liver disease: computed tomography is useful for evaluation.

    PubMed

    Hiraoka, Atsushi; Aibiki, Toshihiko; Okudaira, Tomonari; Toshimori, Akiko; Kawamura, Tomoe; Nakahara, Hiromasa; Suga, Yoshifumi; Azemoto, Nobuaki; Miyata, Hideki; Miyamoto, Yasunao; Ninomiya, Tomoyuki; Hirooka, Masashi; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi; Michitaka, Kojiro

    2015-12-01

    The definition of muscle atrophy (pre-sarcopenia) and its diagnostic criteria have not been well reported. To elucidate the frequency of pre-sarcopenia in chronic liver disease (CLD), we examined clinical features of Japanese CLD patients using abdominal computed tomography (CT) findings. We enrolled 988 CLD (736 with naïve hepatocellular carcinoma) and 372 normal control subjects (NCs). The psoas muscle area index [PI, psoas muscle area at the mid-L3 level in CT (cm(2))/height (m)(2)] was calculated using personal computer software. The cut-off level for pre-sarcopenia was defined as less than two standard deviations (SDs) below the mean PI value in the NCs under 55 years old [males, 45.6 ± 5.7 years (n = 61), 4.24 cm(2)/m(2); females, 47.0 ± 6.1 years (n = 49), 2.50 cm(2)/m(2)]. Elderly was defined as 65 years or older. Clinical features were retrospectively evaluated. In the CLD group (HCV:HBV:HBV and HCV:alcohol:non-HBV and HCV = 652:88:7:82:159), pre-sarcopenia was observed in 15.3% of patients with chronic hepatitis (CH), 24.4% of those with liver cirrhosis (LC) Child-Pugh A, 37.7% of those with LC Child-Pugh B, and 37.1% of those with LC Child-Pugh C. A comparison between NC and CH by age (<55, 55-64, 65-74, ≥75 years) showed that the frequency of pre-sarcopenia was higher in CH regardless of age (1.8 vs. 3.6%, 3.2 vs. 15.9%, 4.9 vs. 13.4%, 14.3 vs. 20.2%, respectively). PI values showed correlations with BMI (r = 0.361), age (r = -0.167), albumin (r = 0.115), and branched-chain amino acids (r = 0.199) (P < 0.01). Retrospective evaluate for pre-sarcopenia was easy to perform with CT findings. Nutrition and exercise instruction should be considered for early stage and even non-elderly CLD as well as LC.

  13. Quantitative analysis of glutathione and cysteine S-conjugates of microcystin-LR in the liver, kidney and muscle of common carp (Cyprinus carpio) in Lake Taihu.

    PubMed

    Wu, Laiyan; Wang, Songbo; Tao, Min; Xie, Ping; Chen, Jun

    2017-04-01

    Tissue distribution of microcystin (MC)-LR-GSH, MC-LR-Cys and MC-LR of omnivorous fish in Lake Taihu was investigated. MC-LR and MC-LR-Cys were detected in liver, kidney and muscle. The concentration of MC-LR in liver and kidney was 0.052 μg g(-1) DW and 0.067 μg g(-1) DW, respectively. MC-LR-Cys appeared to be an important metabolite with average contents of 1.104 μg g(-1) DW and 0.724 μg g(-1) DW in liver and kidney, and the MC-LR-Cys/MC-LR ratio in liver and kidney reaching as high as 21.4 and 10.8. High MC-LR-Cys/MC-LR ratio and a significant correlation between MC-LR-Cys and MC-LR concentration in liver, suggest that liver is more active in detoxification of MC-LR by formation of MC-LR-Cys for omnivorous fish. Furthermore, there might be a balance between the accumulation and depuration/metabolism of MC-LR-Cys in kidney. The MC-LR-Cys can be formed in kidney directly, or transported from liver or other tissues, while the MC-LR-Cys in kidney might be dissociated to MC-LR or excreted. Although MC-LR and its metabolites were scarcely detected in muscle, it is necessary to investigate the distribution of toxic metabolites in edible muscle.

  14. Molecular dissection of DNA sequences and factors involved in slow muscle-specific transcription.

    PubMed

    Calvo, S; Vullhorst, D; Venepally, P; Cheng, J; Karavanova, I; Buonanno, A

    2001-12-01

    Transcription is a major regulatory mechanism for the generation of slow- and fast-twitch myofibers. We previously identified an upstream region of the slow TnI gene (slow upstream regulatory element [SURE]) and an intronic region of the fast TnI gene (fast intronic regulatory element [FIRE]) that are sufficient to direct fiber type-specific transcription in transgenic mice. Here we demonstrate that the downstream half of TnI SURE, containing E box, NFAT, MEF-2, and CACC motifs, is sufficient to confer pan-skeletal muscle-specific expression in transgenic mice. However, upstream regions of SURE and FIRE are required for slow and fast fiber type specificity, respectively. By adding back upstream SURE sequences to the pan-muscle-specific enhancer, we delineated a 15-bp region necessary for slow muscle specificity. Using this sequence in a yeast one-hybrid screen, we isolated cDNAs for general transcription factor 3 (GTF3)/muscle TFII-I repeat domain-containing protein 1 (MusTRD1). GTF3 is a multidomain nuclear protein related to initiator element-binding transcription factor TF II-I; the genes for both proteins are deleted in persons with Williams-Beuren syndrome, who often manifest muscle weakness. Gel retardation assays revealed that full-length GTF3, as well as its carboxy-terminal half, specifically bind the bicoid-like motif of SURE (GTTAATCCG). GTF3 expression is neither muscle nor fiber type specific. Its levels are highest during a period of fetal development that coincides with the emergence of specific fiber types and transiently increases in regenerating muscles damaged by bupivacaine. We further show that transcription from TnI SURE is repressed by GTF3 when overexpressed in electroporated adult soleus muscles. These results suggest a role for GTF3 as a regulator of slow TnI expression during early stages of muscle development and suggest how it could contribute to Williams-Beuren syndrome.

  15. Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue.

    PubMed

    Li, Fengna; Li, Yinghui; Duan, Yehui; Hu, Chien-An A; Tang, Yulong; Yin, Yulong

    2017-02-01

    Skeletal muscle and adipose tissue are the two largest organs in the body. Skeletal muscle is an effector organ, and adipose tissue is an organ that stores energy; in addition, they are endocrine organs that secrete cytokines, namely myokines and adipokines, respectively. Myokines consist of myostatin, interleukin (IL)-8, IL-15, irisin, fibroblast growth factor 21, and myonectin; adipokines include leptin, adiponectin, resistin, chemerin, and visfatin. Furthermore, certain cytokines, such as IL-6 and tumor necrosis factor-α, are released by both skeletal muscle and adipose tissue and exhibit a bioactive effect; thus, they are called adipo-myokines. Recently, novel myokines or adipokines were identified through the secretomic technique, which has expanded our knowledge on the previously unknown functions of skeletal muscle and adipose tissue and provide a new avenue of investigation for obesity treatment or animal production. This review focuses on the roles of and crosstalk between myokines and adipokines in skeletal muscle and adipose tissue that modulate the molecular events in the metabolic homeostasis of the whole body.

  16. Muscle synergies involved in shifts of the center of pressure while standing on a narrow support.

    PubMed

    Wang, Yun; Asaka, Tadayoshi

    2008-05-15

    We investigated multi-muscle synergies during preparation to push a load forward and their changes with different support conditions. We hypothesized that the subjects show unchanged mode structure and would be able to form multi-mode COP stabilizing synergies while standing on an unstable board. Eight healthy subjects participated in the study. Standing subjects performed load-pushing tasks under two conditions, "normal support" and "ML narrow support". Electromyographic (EMG) signals of 12 postural muscles were recorded and analyzed. The participants also performed standard tasks associated with releasing a load. These trials were used to identify muscle groupings (M-modes) associated with shifts of the center of pressure (COP) and relations between small changes in the M-modes and COP shifts in different support conditions. The subjects showed unchanged mode structure across different support conditions. The framework of the uncontrolled manifold hypothesis was used to partition the EMG variance across load-pushing trials into two components that kept constant and changed the COP coordinates in the anterior-posterior (AP) direction. This analysis has allowed us associate changes in the contribution of muscles with COP shifts under different support conditions. Different time profiles of the synergies were observed related to the COP shifts across conditions. This outcome supports a view that indices of multi-muscle (multi-M-mode) synergies can show anticipatory changes in preparation for a predictable perturbation.

  17. Involvement of the Interosseous and Lumbrical Muscle-Tendon Units in the Lateral and Spiral Cords in Dupuytren's Disease of the Middle Fingers.

    PubMed

    Thoma, Achilleas; Karpinski, Marta

    2017-07-01

    The nature of intrinsic muscle involvement in Dupuytren's disease of the middle fingers (long and ring) remains poorly characterized. Over the years, the authors have observed that both the spiral and lateral digital cords in the middle fingers receive contribution from intrinsic muscle-tendon units. This report describes the anatomical characteristics and frequency of intrinsic muscle-tendon unit involvement in Dupuytren's disease of the middle fingers. Intrinsic muscle involvement in the middle digits was recorded in the operative reports of patients undergoing Dupuytren's surgery between October of 2013 and February of 2016. The anatomical variations of diseased fascia were delineated and classified. Of the 113 digits with Dupuytren's contracture operated on during this period, 52 involved the middle fingers (12 long and 40 ring fingers). Intrinsic muscles were found to be involved in the contracture of 14 of these digits. Two unique contracture patterns were identified: type I contracture, which involves a lateral digital cord originating from intrinsic muscle-tendon units and contracting only the proximal interphalangeal joint; and type II contracture, which involves a spiral cord receiving contribution from intrinsic muscle-tendon units and contracting both the metacarpophalangeal and proximal interphalangeal joints. The frequency of type I and type II contractures was 6 percent and 12 percent, respectively. Intrinsic hand muscles may contribute to Dupuytren's disease in the middle digits, and the authors suggest resecting cords as close as possible to their musculotendinous origin to improve postoperative outcomes.

  18. An uncoupling protein homologue putatively involved in facultative muscle thermogenesis in birds.

    PubMed Central

    Raimbault, S; Dridi, S; Denjean, F; Lachuer, J; Couplan, E; Bouillaud, F; Bordas, A; Duchamp, C; Taouis, M; Ricquier, D

    2001-01-01

    The cDNA of an uncoupling protein (UCP) homologue was obtained by screening a chicken skeletal-muscle library. The predicted 307-amino-acid sequence of avian UCP (avUCP) is 55, 70, 70 and 46% identical with mammalian UCP1, UCP2 and UCP3 and plant UCP respectively. avUCP mRNA expression is restricted to skeletal muscle and its abundance was increased 1.3-fold in a chicken line showing diet-induced thermogenesis, and 3.6- and 2.6-fold in cold-acclimated and glucagon-treated ducklings developing muscle non-shivering thermogenesis respectively. The present data support the implication of avUCP in avian energy expenditure. PMID:11171038

  19. Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy.

    PubMed

    Castillero, Estibaliz; Akashi, Hirokazu; Wang, Catherine; Najjar, Marc; Ji, Ruiping; Kennel, Peter J; Sweeney, H Lee; Schulze, Paul C; George, Isaac

    2015-01-30

    Myostatin (MSTN), a negative regulator of muscle growth and size, is increased after acute myocardial infarction (AMI) but timing of upregulation after injury is not known. In this study, we investigated the timing of the MSTN/AKT/p38 pathway activation in heart and skeletal muscle after AMI, as well as the potential effect of cardiac injury-related MSTN endocrine signaling on skeletal muscle and other circulating growth factors. Coronary artery ligation was performed in C57BL/6 mice at age 8 weeks to induce AMI. Mice were sacrificed at different time points (10 m, 1 h, 2 h, 6 h, 12 h, 24 h, 1 week, 2 weeks, 1 months and 2 months) after surgery (n=3 per time point, n=18 total). Cardiac and circulating MSTN upregulation occurred as early as 10 min after AMI. Two months after AMI, increased cardiac MSTN/SMAD2,3 and p38 together with decreased IGF-1/AKT signaling suggest an anti-hypertrophic profile. In skeletal muscle, an absence of local MSTN increase was accompanied by increased MSTN-dependent SMAD2,3 signaling, suggestive of paracrine effects due to cardiac-derived MSTN. Protein degradation by the ubiquitin-proteasome system in the skeletal muscle was also evident. Serum from 24h post-MI mice effectively induced a MSTN-dependent increase in atrogin1 and MuRF1. Our study shows that cardiac MTSN activation occurs rapidly after cardiac ischemia and may be involved in peripheral protein degradation in the skeletal muscle by activating atrogin1 and MuRF1. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Involvement of mTOR in Type 2 CRF Receptor Inhibition of Insulin Signaling in Muscle Cells.

    PubMed

    Chao, Hongxia; Li, Haochen; Grande, Rebecca; Lira, Vitor; Yan, Zhen; Harris, Thurl E; Li, Chien

    2015-06-01

    Type 2 corticotropin-releasing factor receptor (CRFR2) is expressed in skeletal muscle and stimulation of the receptor has been shown to inhibit the effect of insulin on glucose uptake in muscle cells. Currently, little is known about the mechanisms underlying this process. In this study, we first showed that both in vivo and in vitro CRFR2 expression in muscle was closely correlated with insulin sensitivity, with elevated receptor levels observed in insulin resistant muscle cells. Stimulation of CRFR2 by urocortin 2 (Ucn 2), a CRFR2-selective ligand, in C2C12 myotubes greatly attenuated insulin-induced glucose uptake. The inhibitory effect of CRFR2 signaling required cAMP production and is involved the mammalian target of rapamycine pathway, as rapamycin reversed the inhibitory effect of CRFR2 stimulation on insulin-induced glucose uptake. Moreover, stimulation of CRFR2 failed to inhibit glucose uptake in muscle cells induced by platelet-derived growth factor, which, similar to insulin, signals through Akt-mediated pathway but is independently of insulin receptor substrate (IRS) proteins to promote glucose uptake. This result argues that CRFR2 signaling modulates insulin's action likely at the levels of IRS. Consistent with this notion, Ucn 2 reduced insulin-induced tyrosine phosphorylation of IRS-1, and treatment with rapamycin reversed the inhibitory effect of Ucn 2 on IRS-1 and Akt phosphorylation. In conclusion, the inhibitory effect of CRFR2 signaling on insulin action is mediated by cAMP in a mammalian target of rapamycine-dependent manner, and IRS-1 is a key nodal point where CRFR2 signaling modulates insulin-stimulated glucose uptake in muscle cells.

  1. Comparison of total lipids and fatty acids from liver, heart and abdominal muscle of scalloped (Sphyrna lewini) and smooth (Sphyrna zygaena) hammerhead sharks.

    PubMed

    Davidson, Bruce Clement; Nel, Wynand; Rais, Afsha; Namdarizandi, Vahid; Vizarra, Scott; Cliff, Geremy

    2014-01-01

    Liver, heart and abdominal muscle samples from scalloped (Sphyrna lewini) and smooth (Sphyrna zygaena) hammerhead sharks were analysed to characterise their lipid and fatty acid profiles. Samples were compared both between and within species, but there were no significant differences in total lipids for either comparison, although much greater total amounts were found in the liver samples. Within the individual fatty acids, the only significant differences were greater amounts of 22:6n-3, total n-3 polyunsaturates and total polyunsaturates in smooth, when compared to scalloped, hammerhead liver. This may reflect the more wide spread distribution of this species into cooler waters. Within both species the liver levels of the same fatty acid fractions decreased from spring to summer, which may correlate with changes in fatty acid profile to adapt to any differences in amount or species of prey consumed, or other considerations, eg. buoyancy, however there was no data to clarify this.

  2. Involvement of oxidative stress in tri-ortho-cresyl phosphate-induced liver injury in male mice.

    PubMed

    Xu, L L; Long, C Y; Wang, J L; Yu, M; Chen, J X

    2016-10-01

    Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners, and flame retardants in industry and reported to have delayed neurotoxicity and reproductive toxicology in animals. However, it remains to be elusive whether TOCP induces liver injury. In this study, male mice were orally administered different concentrations of TOCP (100, 200, or 400 mg/kg/day) for 28 days. Histological examination showed that TOCP led to serious hepatocellular injury. In addition, administration of TOCP induced a marked elevation in the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice. The content of malondialdehyde (MDA) was increased significantly in the liver after the mice were treated with TOCP; while there was a dramatic decrease in the content of glutathione (GSH) and the activities of antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). TOCP inhibited viability of mouse liver cancer Hepa 1-6 cells in a dose-dependent manner. Meanwhile, TOCP significantly increased MDA content and inhibited GSH content and the activities of SOD and GSH-PX in the cells, respectively. Oxidative stress dramatically inhibited viability of Hepa 1-6 cells; while inhibition of oxidative stress by N-acetyl-l-cysteine could rescue the cell viability inhibited by TOCP to a certain extent. In summary, oxidative stress might be involved in TOCP-induced hepatocellular injury in male mice. © The Author(s) 2016.

  3. Regulation of Glycolytic Metabolism by Autophagy in Liver Cancer Involves Selective Autophagic Degradation of HK2 (hexokinase 2).

    PubMed

    Jiao, Lin; Zhang, Hai-Liang; Li, Dan-Dan; Yang, Ke-Li; Tang, Jun; Li, Xuan; Ji, Jiao; Yu, Yan; Wu, Rui-Yan; Ravichandran, Senthilkumar; Liu, Jian-Jun; Feng, Gong-Kan; Chen, Min-Shan; Zeng, Yi-Xin; Deng, Rong; Zhu, Xiao-Feng

    2017-10-05

    Impaired macroautophagy/autophagy and high levels of glycolysis are prevalent in liver cancer. However, it remains unknown whether there is a regulatory relationship between autophagy and glycolytic metabolism. In this study, by utilizing cancer cells with basal or impaired autophagic flux, we demonstrated that glycolytic activity is negatively correlated with autophagy level. The autophagic degradation of HK2 (hexokinase 2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate, was found to be involved in the regulation of glycolysis by autophagy. The Lys63-linked ubiquitination of HK2 catalyzed by the E3 ligase TRAF6 was critical for the subsequent recognition of HK2 by the autophagy receptor protein SQSTM1/p62 for the process of selective autophagic degradation. In a tissue microarray of human liver cancer, the combination of high HK2 expression and high SQSTM1 expression was shown to have biological and prognostic significance. Furthermore, 3-BrPA, a pyruvate analog targeting HK2, significantly decreased the growth of autophagy-impaired tumors in vitro and in vivo (p<0.05). By demonstrating the regulation of glycolysis by autophagy through the TRAF6- and SQSTM1-mediated ubiquitination system, our study may open an avenue for developing a glycolysis-targeting therapeutic intervention for treatment of autophagy-impaired liver cancer.

  4. Recognition of lactoferrin and aminopeptidase M-modified lactoferrin by the liver: involvement of proteoglycans and the remnant receptor.

    PubMed Central

    Ziere, G J; Kruijt, J K; Bijsterbosch, M K; van Berkel, T J

    1996-01-01

    1. Lactoferrin and aminopeptidase M-modified lactoferrin (APM-lactoferrin; which lacks its 14 N-terminal amino acids) inhibit the liver uptake of lipoprotein remnant. In the present study, the role of proteoglycans in the initial interaction of beta-migrating very-low-density lipoprotein (beta-VLDL), native and APM-lactoferrin with isolated rat parenchymal liver cells was investigated. Treatment of the cells with chondroitinase lowered the Kd of lactoferrin binding (from 10 to 2.4 microM), and the number of sites/cell (from 20 x 10(6) to 7 x 10(6)), while heparinase treatment did not affect the binding. The binding characteristics of APM-lactoferrin and beta-VLDL were not altered by treatment of the cells with chondroitinase or heparinase. It is concluded that proteoglycans are not involved in the initial binding of APM-lactoferrin and beta-VLDL to parenchymal cells, while chondroitin sulphate proteoglycans are mainly responsible for the massive, low-affinity binding of native lactoferrin..2. The binding of lactoferrin, APM-lactoferrin and beta-VLDL to parenchymal liver cells was not influenced by the glutathione S-transferase-receptor-associated protein (GST-RAP) (97.2% +/- 4.0%, 95.5 +/- 3.7% and 98.5% of the control binding), while the binding of alpha 2-macroglobulin was fully blocked at 10 micrograms/ml GST-RAP (1.8 +/- 0.5% of the control binding). Since GST-RAP blocks the binding of all the known ligands to the low-density lipoprotein (LDL)-receptor-related protein (LRP), it is concluded that LRP is not the initial primary recognition site for lactoferrin, APM-lactoferrin and beta-VLDL on parenchymal liver cells. 3. We showed earlier that.APM-lactoferrin, as compared with lactoferrin, is a more effective inhibitor of the liver uptake of lipoprotein remnants (49.4 +/- 4.0% versus 80.8 +/- 4.8% of the control at 500 micrograms/ml respectively). We found in the present study that beta-VLDL is able to inhibit the binding of APM-lactoferrin to parenchymal liver

  5. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice

    PubMed Central

    Ferreira, Sandra M.; Vettorazzi, Jean F.; Nardelli, Tarlliza R.; Araujo, Hygor N.; Santos, Gustavo J.; Carneiro, Everardo M.; Boschero, Antonio C.; Rezende, Luiz F.; Costa-Júnior, José M.

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60–70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe. PMID:27467214

  6. Meta-Analysis: Diagnostic Accuracy of Antinuclear Antibodies, Smooth Muscle Antibodies and Antibodies to a Soluble Liver Antigen/Liver Pancreas in Autoimmune Hepatitis

    PubMed Central

    Chen, Juan; Chen, Wei-Xian

    2014-01-01

    Background Antinuclear antibodies (ANA), smooth muscle antibodies (SMA) and antibodies to a soluble liver antigen/liver pancreas (anti-SLA/LP) are useful markers that can help clinicians to diagnose and classify autoimmune hepatitis (AIH). Objectives To determine whether ANA, SMA and anti-SLA/LP help to accurately diagnose patients with AIH. Search strategy The PubMed, CNKI, WANFANG, and SinoMed databases were accessed to retrieve studies published in English and Chinese. Studies published up to October 2013 were reviewed. Selection criteria Studies on the diagnostic value of ANA, SMA or anti-SLA/LP in the diagnosis of known or suspected AIH were included. Data collection and analysis Two authors evaluated studies independently and rated their methodological quality using quality assessment of diagnostic accuracy studies (QUADAS) tools; relevant data were abstracted. The random-effects method was used to summarize sensitivities, specificities, positive and negative likelihood ratios, and diagnostic odds ratios (DORs) from all 29 studies. Results The pooled sensitivity, specificity, positive and negative likelihood ratios, and DOR for ANA were 0.650 (95% confidence interval [CI], 0.619 to 0.680), 0.751 (95%CI, 0.737 to 0.764), 3.030 (95%CI, 2.349 to 3.910), 0.464 (95%CI, 0.356 to 0.604), and 7.380 (95%CI, 4.344 to 12.539), respectively. For SMA, the values were 0.593 (95%CI, 0.564 to 0.621), 0.926 (95%CI, 0.917 to 0.934), 11.740 (95%CI, 7.379 to 18.678), 0.449 (95%CI, 0.367 to 0.549), and 31.553 (95%CI, 17.147 to 58.060), respectively. Finally, for anti-SLA/LP, the values were 0.194 (95%CI, 0.168 to 0.222), 0.989 (95%CI, 0.985 to 0.993), 11.089 (95%CI, 7.601 to 16.177), 0.839 (95%CI, 0.777 to 0.905), and 16.867 (95%CI, 10.956 to 25.967), respectively. Authors’ conclusions ANA provided moderate sensitivity and specificity, while SMA gave moderate sensitivity and high specificity, and anti-SLA/LP exhibited low sensitivity and high specificity. All three antibodies

  7. The Role of Muscle Insulin Resistance in the Pathogenesis of Atherogenic Dyslipidemia and Nonalcoholic Fatty Liver Disease Associated with the Metabolic Syndrome

    PubMed Central

    Jornayvaz, François R.; Samuel, Varman T.; Shulman, Gerald I.

    2013-01-01

    The metabolic syndrome is a clustering of cardiovascular risk factors, including insulin resistance, abdominal obesity, dyslipidemia, and hypertension, and is associated with other comorbidities such as a proinflammatory state and nonalcoholic fatty liver disease (NAFLD). Its prevalence is high, especially among developed countries, and mainly reflects overnutrition and sedentary lifestyle. Moreover, the developing countries are not spared, as obesity and its related problems such as the metabolic syndrome are increasing quickly. We review the potential primary role of skeletal muscle insulin resistance in the pathophysiology of the metabolic syndrome, showing that in lean, young, insulin-resistant individuals, impaired muscle glucose transport and glycogen synthesis redirect energy derived from carbohydrate into hepatic de novo lipogenesis, promoting the development of atherogenic dyslipidemia and NAFLD. The demonstration of a link between skeletal muscle insulin resistance and the metabolic syndrome offers opportunities in targeting early defects in muscle insulin action in order to counteract the development of the disease and its related complications. PMID:20645852

  8. Evidence that lysosomes are not involved in the degradation of myofibrillar proteins in rat skeletal muscle.

    PubMed Central

    Lowell, B B; Ruderman, N B; Goodman, M N

    1986-01-01

    To examine the role of lysosomes in the degradation of skeletal-muscle myofibrillar proteins, we measured the release of N tau-methylhistidine from perfused muscle of starved and fed rats in the presence or absence of agents that inhibit lysosomal proteinase activity. After 1 day of starvation, the release of N tau-methylhistidine by perfused muscle of 4-, 8- and 24-week-old rats increased by 322, 159 and 134% respectively. On the other hand, total protein breakdown, assessed by tyrosine release, increased by 62, 20 and 20% respectively. Inhibitors of lysosomal proteinases as well as high concentrations of insulin or amino acids failed to diminish the release of N tau-methylhistidine by perfused muscle of starved and fed rats, despite a 25-35% inhibition of total protein breakdown. The data strongly suggest that the complete breakdown of myofibrillar proteins occurs via a non-lysosomal pathway. They also suggest that total proteolysis, which primarily reflects non-myofibrillar protein breakdown, occurs at least in part within lysosomes. PMID:3707546

  9. TNF-α is involved in activating DNA fragmentation in skeletal muscle

    PubMed Central

    Carbó, N; Busquets, S; van Royen, M; Alvarez, B; López-Soriano, F J; Argilés, J M

    2002-01-01

    Intraperitoneal administration of 100 μg kg−1 (body weight) of tumour necrosis factor-α to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-α-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-α-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-α receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-α partly mediates DNA fragmentation during experimental cancer-associated cachexia. British Journal of Cancer (2002) 86, 1012–1016. DOI: 10.1038/sj/bjc/6600167 www.bjcancer.com © 2002 Cancer Research UK PMID:11953838

  10. Levels of Metals in Kidney, Liver, and Muscle Tissue and their Influence on the Fitness for the Consumption of Wild Boar from Western Slovakia.

    PubMed

    Gašparík, Jozef; Binkowski, Łukasz J; Jahnátek, Andrej; Šmehýl, Peter; Dobiaš, Milan; Lukáč, Norbert; Błaszczyk, Martyna; Semla, Magdalena; Massanyi, Peter

    2017-06-01

    Due to environmental pollution, wild animals are exposed to various pollutants. Some game animals, such as wild boars are used by people for food, but their meat is not evaluated regarding pollution transfer, since they are unavailable on the official market. The aim of this paper is to present the concentrations of chosen metals (Cd, Co, Cu, Hg, Pb, and Zn) in the kidneys, liver, and muscles of wild boars (n = 40) hunted in eastern Slovakia, as derivatives of physiological distribution and anthropogenic pollution. We found that sex was not a statistically significant factor for metal concentrations. Tissue differences were observed for all the metals studied except for Co. Cd, Cu, and Hg showed the highest median concentrations in kidney tissue with the lowest in muscle tissue (2.73, 3.78, and 0.061 μg/g w.w., respectively). The highest Zn median concentration was noted in the liver tissue with the lowest in muscle tissue. Co and Cu concentrations varied according to the age groups. Correlations between metal concentrations in muscle and kidney tissue were not especially strong; such relationships were not found in liver tissue. Among all the potential relationships of the given metal concentrations between tissues, the only significant relationship, albeit weak, was noted for Pb in muscle and liver tissue. The concentrations found seem not to be extremely high, but according to EU maximum permitted residue levels for Cd and Pb concentrations in meat, none of the samples studied was fully fit for human consumption. TWI and risk was also excessive for both metals.

  11. Carcinoid Heart Disease without Liver Involvement Caused by a Primary Ovarian Carcinoid Tumour.

    PubMed

    Agarwal, Chirag; Goel, Sunny; Stern, Eric; Warner, Richard; Castillo, Javier; Croft, Lori; Lavine, Ronald; Zacks, Jerome

    2015-07-01

    Carcinoid heart disease, caused by primary ovarian carcinoid tumour, is a rare form of valvular heart disease. This form of heart disease usually presents with symptoms of right-sided valvular dysfunction, ultimately leading to right-sided heart failure. This entity is unique as it develops in the absence of liver metastasis. We report a case of 75 year-old woman with primary ovarian carcinoid tumour who presented with symptoms of severe right-sided heart failure and successfully underwent pulmonic and tricuspid valve replacement along with a right ventricular (RV) outflow patch enlargement. This patient later underwent uneventful resection of the primary ovarian carcinoid tumour, with complete resolution of her symptoms.

  12. Mechanism Involved in Trichloroethylene-Induced Liver Cancer: Importance to Environmental Cleanup

    SciTech Connect

    Bull, Richard J.; Thrall, Brian D.

    1999-06-01

    The objective of this project is to develop critical data for improving risk-based cleanup standards for trichloroethylene (TCE). Importance to DOE. Cleanup costs for chlorinated solvents found on DOE sites are most frequently driven by TCE because it is the most widespread contaminant and is generally present at the highest concentrations. Data that would permit increases in risk-based standards for TCE would reduce complex wide cleanup costs by hundreds of millions of dollars. Current Regulatory Actions that Research will Impact. EPA is currently reviewing its risk assessment for TCE. Richard J. Bull has worked with EPA on this review by writing the mode of action section of their determination. A presentation by James Cogliano of EPA at the 1999 Annual Society of Toxicology Meeting indicates that they have accepted the concept of nonlinear extrapolation for liver tumor induction by TCE. This project will end in FY 1999 with its major technical and policy objectives satisfied.

  13. Split-hand plus sign in ALS: differential involvement of the flexor pollicis longus and intrinsic hand muscles.

    PubMed

    Menon, Parvathi; Bae, Jong Seok; Mioshi, Eneida; Kiernan, Matthew C; Vucic, Steve

    2013-05-01

    The flexor pollicis longus (FPL), a key muscle involved in fractionated thumb movements, may be relatively spared in amyotrophic lateral sclerosis (ALS) compared to the thenar group of muscles, termed the split-hand plus sign. Consequently, the diagnostic utility of the split-hand plus sign was prospectively assessed in ALS. In total, 103 patients (37 ALS and 66 non-ALS) with neuromuscular symptoms underwent assessment of FPL and APB strength using the Medical Research Council (MRC) score. A median nerve strength index (MSI) was developed to quantify differential involvement by expressing the APB strength score as a fraction of the FPL strength score. The APB muscle strength was significantly reduced compared to FPL strength in ALS patients (p < 0.0001), but was comparable in the non-ALS disorders (p = 0.91). In addition, there was a significant reduction of MSI scores in ALS patients (MSIALS 0.8; MSInon-ALS 1.0, p < 0.01). Analysis of receiver operating characteristic (ROC) curves disclosed that MSI < 0.9 exhibited an area under the curve of 0.86 (p < 0.001) with a sensitivity of 85% and specificity of 86% for limb-onset ALS. In conclusion, split-hand plus sign distinguished ALS from non-ALS neuromuscular disorders, thereby suggesting a diagnostic utility of this novel clinical sign in ALS.

  14. Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women

    PubMed Central

    Kars, Marleen; Yang, Ling; Gregor, Margaret F.; Mohammed, B. Selma; Pietka, Terri A.; Finck, Brian N.; Patterson, Bruce W.; Horton, Jay D.; Mittendorfer, Bettina; Hotamisligil, Gökhan S.; Klein, Samuel

    2010-01-01

    OBJECTIVE Insulin resistance is commonly associated with obesity. Studies conducted in obese mouse models found that endoplasmic reticulum (ER) stress contributes to insulin resistance, and treatment with tauroursodeoxycholic acid (TUDCA), a bile acid derivative that acts as a chemical chaperone to enhance protein folding and ameliorate ER stress, increases insulin sensitivity. The purpose of this study was to determine the effect of TUDCA therapy on multiorgan insulin action and metabolic factors associated with insulin resistance in obese men and women. RESEARCH DESIGN AND METHODS Twenty obese subjects ([means ± SD] aged 48 ± 11 years, BMI 37 ± 4 kg/m2) were randomized to 4 weeks of treatment with TUDCA (1,750 mg/day) or placebo. A two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusions and muscle and adipose tissue biopsies were used to evaluate in vivo insulin sensitivity, cellular factors involved in insulin signaling, and cellular markers of ER stress. RESULTS Hepatic and muscle insulin sensitivity increased by ∼30% (P < 0.05) after treatment with TUDCA but did not change after placebo therapy. In addition, therapy with TUDCA, but not placebo, increased muscle insulin signaling (phosphorylated insulin receptor substrateTyr and AktSer473 levels) (P < 0.05). Markers of ER stress in muscle or adipose tissue did not change after treatment with either TUDCA or placebo. CONCLUSIONS These data demonstrate that TUDCA might be an effective pharmacological approach for treating insulin resistance. Additional studies are needed to evaluate the target cells and mechanisms responsible for this effect. PMID:20522594

  15. Evidence for involvement of multiple forms of cytochrome P-450 in aflatoxin B sup 1 metabolism in human liver

    SciTech Connect

    Forrester, L.M.; Wolf, C.R. ); Neal, G.E.; Judah, D.J. )

    1990-11-01

    Liver cancer is a major cause of premature death in many areas of Africa and Asia and its incidence is strongly correlated with exposure to aflatoxin B{sub 1} (AFB{sub 1}). Because AFB{sub 1} requires metabolic activation to achieve a biological response, there is a need for detailed knowledge of the mechanism of activation to assess individual risk. The authors carried out an extensive study using a total of 19 human liver samples to determine the individual variability in the metabolism of the toxin to mutagenic or detoxification products and to identify the specific cytochrome P-450 forms involved in these processes. Metabolism to the toxic 8,9-epoxide or to products mutagenic in the Ames test was found to exhibit very large individual variation. These data demonstrate that, although P450IIIA probably plays an important role in AFB{sub 1} activation, several other cytochrome P-450 forms have the capacity to activate the toxin. Similar considerations apply to detoxifying metabolism to aflatoxin Q{sub 1} and aflatoxin M{sub 1}. The levels of expression of many of the forms of cytochrome P-450 involved in AFB{sub 1} metabolism are known to be highly sensitive to environmental factors. This indicates that such factors will be an important determinant in individual susceptibility to the tumorigenic action of AFB{sub 1}.

  16. Effects of gestation and transition diets, piglet birth weight, and fasting time on depletion of glycogen pools in liver and 3 muscles of newborn piglets.

    PubMed

    Theil, P K; Cordero, G; Henckel, P; Puggaard, L; Oksbjerg, N; Sørensen, M T

    2011-06-01

    The experiment was conducted to assess the effects of maternal nutrition in late gestation on glycogen pools of newborn piglets of different birth weights and to assess how rapidly the glycogen pools in the liver and 3 muscles are mobilized during fasting. Until d 108 of gestation, 48 sows were fed a gestation standard diet (GSD) with low dietary fiber (DF, 17.1%), or 1 of 3 diets with high DF (32.3 to 40.4%) consisting of pectin residue (GPR), potato pulp (GPP), or sugar-beet pulp (GSP). From d 108 until farrowing, sows were fed 1 of 6 transition diets with low or high dietary fat: one group received a standard diet (TSD; control) containing 3% animal fat, another group received the TSD diet + 2.5 g/d of hydroxy-methyl butyrate as topdressing (THB), and 4 other groups received diets with 8% added fat from coconut oil (TCO), sunflower oil (TSO), fish oil (TFO), or 4% octanoic acid + 4% fish oil (TOA). Two piglets per litter (the second and fifth born) were blood sampled, and 1 was killed immediately after birth, whereas the other, depending on the litter, was killed after 12, 24, or 28.5 to 36 h (mean 32.5 h) of fasting. Samples of liver, LM, M. semimembranousus (SM), and M. diaphragm (DP) were collected and analyzed for glycogen concentration. No dietary effects (P > 0.20) on glycogen concentrations in liver, LM, SM, or DP were observed. The weight of the liver was affected by gestation diet (P < 0.05) and was greater in GSD and GSP piglets (36.7 and 36.3 g) than in GPR piglets (32.6 g), and intermediate (33.6 g) in GPP piglets. Liver weight, estimated muscle mass, and glycogen pools (P < 0.001) were affected by birth weight, whereas glycogen concentrations in liver and LM, SM, and DP muscles were not (P > 0.05). Liver weight; glycogen concentrations in liver, LM, SM, and DP; and glycogen pools in liver and muscles decreased (P < 0.001) with increasing duration of fasting, and at 32.5 h of fasting, glycogen concentration was reduced by 80% in liver, 64% in DP, 46

  17. Effects of adrenal hormones on the expression of adiponectin and adiponectin receptors in adipose tissue, muscle and liver.

    PubMed

    de Oliveira, Cristiane; Iwanaga-Carvalho, Carla; Mota, João F; Oyama, Lila M; Ribeiro, Eliane B; Oller do Nascimento, Cláudia M

    2011-11-01

    Adiponectin, an insulin-sensitive hormone that is primarily synthesized in adipose tissue, exerts its effects by binding to two receptors, adipoR1 and adipoR2. Little is known regarding the effects of glucocorticoids on the expression of adiponectin receptors. Male Wistar rats were bilaterally adrenalectomized and treated with dexamethasone (0.2 mg/100 g) twice daily for 3 days. To analyze the potential effects of glucocorticoids, rats received two daily injections of the glucocorticoid receptor antagonist (RU-486, 5.0 mg) over the course of 3 days. Additionally, 3T3-L1 adipocytes and C2C12 myotubes were treated with dexamethasone, adrenaline or RU-486. The gene expression of adiponectin, adipoR1 and adipoR2 was determined by real-time PCR, and protein secretion was examined by Western blotting using lysates from retroperitoneal, epididymal and subcutaneous adipose tissue depots, liver and muscle. In rats, excess glucocorticoids increased the levels of insulin in serum and decreased serum adiponectin concentrations, whereas adrenalectomy decreased the mRNA expression of adiponectin (3-fold) and adipoR2 (7-fold) in epididymal adipose tissue and increased adipoR2 gene expression in muscle (3-fold) compared to control group sham-operated. Dexamethasone treatment did not reverse the effects of adrenalectomy, and glucocorticoid receptor blockade did not reproduce the effects of adrenalectomy. In 3T3-L1 adipocytes, dexamethasone and adrenaline both increased adipoR2 mRNA levels, but RU-486 reduced adipoR2 gene expression in vitro. Dexamethasone treatment induces a state of insulin resistance but does not affect adiponectin receptor expression in adipose tissue. However, the effects of catecholamines on insulin resistance may be due to their effects on adipoR2. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Effect of Intermittent Hypoxia and Rimonabant on Glucose Metabolism in Rats: Involvement of Expression of GLUT4 in Skeletal Muscle

    PubMed Central

    Wang, Xiaoya; Yu, Qin; Yue, Hongmei; Zeng, Shuang; Cui, Fenfen

    2015-01-01

    Background Obstructive sleep apnea (OSA) and its main feature, chronic intermittent hypoxia (IH) during sleep, is closely associated with insulin resistance (IR) and diabetes. Rimonabant can regulate glucose metabolism and improve IR. The present study aimed to assess the effect of IH and rimonabant on glucose metabolism and insulin sensitivity, and to explore the possible mechanisms. Material/Methods Thirty-two rats were randomly assigned into 4 groups: Control group, subjected to intermittent air only; IH group, subjected to IH only; IH+NS group, subjected to IH and treated with normal saline; and IH+Rim group, subjected to IH and treated with 10 mg/kg/day of rimonabant. All rats were killed after 28 days of exposure. Then, the blood and skeletal muscle were collected. We measured fasting blood glucose levels, fasting blood insulin levels, and the expression of glucose transporter 4 (GLUT4) in both mRNA and protein levels in skeletal muscle. Results IH can slow weight gain, increase serum insulin level, and reduce insulin sensitivity in rats. The expressions of GLUT4 mRNA, total GLUT4, and plasma membrane protein of GLUT4 (PM GLUT4) in skeletal muscle were decreased. Rimonabant treatment was demonstrated to improve weight gain and insulin sensitivity of the rats induced by IH. Rimonabant significantly upregulated the expression of GLUT4 mRNA, PM GLUT4, and total GLUT4 in skeletal muscle. Conclusions The present study demonstrates that IH can cause IR and reduced expression of GLUT4 in both mRNA and protein levels in skeletal muscle of rats. Rimonabant treatment can improve IH – induced IR, and the upregulation of GLUT4 expression may be involved in this process. PMID:26503060

  19. Differences in the expression of genes involved in skeletal muscle proteolysis between broiler and layer chicks during food deprivation.

    PubMed

    Saneyasu, Takaoki; Kimura, Sayaka; Inui, Mariko; Yoshimoto, Yu; Honda, Kazuhisa; Kamisoyama, Hiroshi

    2015-08-01

    Genetic selection results in a higher growth rate and meat yield in broiler chickens than in layer chickens. We herein demonstrated differences in the effects of 24 h of fasting on the expression of genes involved in skeletal muscle proteolysis between broiler and layer chicks. The mRNA levels of proteolysis-related genes were analyzed in the pectoralis major muscle of 14-day-old chicks after 0 or 24 h of fasting. The mRNA levels of ubiquitin ligases such as atrogin-1 and muscle RING finger-1 (MuRF-1) as well as transcription factor forkhead box class O (FOXO) 1 were significantly increased by fasting in broiler and layer chicks, suggesting that the FOXO1-induced ubiquitin-proteasome system, a major proteolytic system in skeletal muscles, was activated by fasting in both chicks. The mRNA levels of atrogin-1 were significantly lower in broiler chicks than in layer chicks after fasting. Furthermore, the mRNA levels of insulin-like growth factor-1 were significantly decreased by fasting in layer chicks, but not in broiler chicks. The mRNA levels of FOXO3 were significantly increased by fasting in layer chicks, but not in broiler chicks. Therefore, the ubiquitin-proteasome system did not appear to have been fully upregulated in broiler chicks. These results suggest that differences in the expression of genes related to the ubiquitin-proteasome system in skeletal muscle proteolysis between broiler and layer chicks during food deprivation are one of the causes of the high growth rate in broiler chickens.

  20. Molecular characterization of betaine-homocysteine methyltransferase 1 from the liver, and effects of aestivation on its expressions and homocysteine concentrations in the liver, kidney and muscle, of the African lungfish, Protopterus annectens.

    PubMed

    Ong, Jasmine L Y; Woo, Jia M; Hiong, Kum C; Ching, Biyun; Wong, Wai P; Chew, Shit F; Ip, Yuen K

    2015-05-01

    Homocysteine accumulation has numerous deleterious effects, and betaine-homocysteine S-methyltransferase (BHMT) catalyses the synthesis of methionine from homocysteine and betaine. This study aimed to determine homocysteine concentrations, and mRNA expression levels and protein abundances of bhmt1/Bhmt1 in the liver, kidney and muscle of the African lungfish, Protopterus annectens, during the induction (6 days), maintenance (6 months) or arousal (3 days after arousal) phase of aestivation. The homocysteine concentration decreased significantly in the liver of P. annectens after 6 days or 6 months of aestivation, but it returned to the control level upon arousal. By contrast, homocysteine concentrations in the kidney and muscle remained unchanged during the three phases of aestivation. The complete coding cDNA sequence of bhmt1 from P. annectens consisted of 1236 bp, coding for 412 amino acids. The Bhmt1 from P. annectens had a close phylogenetic relationship with those from tetrapods and Callorhinchus milii. The expression of bhmt1 was detected in multiple organs/tissues of P. annectens, and this is the first report on the expression of bhmt1/Bhmt1 in animal skeletal muscle. The mRNA and protein expression levels of bhmt1/Bhmt1 were up-regulated in the liver of P. annectens during the induction and maintenance phases of aestivation, possibly to regulate the hepatic homocysteine concentration. The significant increase in hepatic Bhmt1 protein abundance during the arousal phase could be a response to increased cellular methylation for the purpose of tissue reconstruction. Unlike the liver, Bhmt1 expression in the kidney and muscle of P. annectens was regulated translationally, and its up-regulation could be crucial to prevent homocysteine accumulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Striated muscle involvement in experimental oral infection by herpes simplex virus type 1.

    PubMed

    Gonzalez, María Inés; Sanjuan, Norberto A

    2013-07-01

    Herpes simplex virus type 1 is one of the most frequent causes of oral infection in humans, especially during early childhood. Several experimental models have been developed to study the pathogenesis of this virus but all of them employed adult animals. In this work, we developed an experimental model that uses mice younger than 4 days old, to more closely resemble human infection. Mice were infected subcutaneously with the prototype strain McIntyre of Herpes simplex-1, and the progression of infection was studied by immunoperoxidase. All animals died within 24-72 h post-infection, while viral antigens were found in the oral epithelium, nerves and brain. The most striking result was the finding of viral antigens in the nucleus and cytoplasm of cells belonging to striated muscles. Organotypic cultures of striated muscles were performed, and viral replication was observed in them by immunocytochemistry, electron microscopy and viral isolation. We conclude that the infection of striated muscles is present from the onset of oral infection and, eventually, could explain some clinical observations in humans.

  2. Mapping and expression analyses during porcine foetal muscle development of 12 genes involved in histone modifications.

    PubMed

    Peng, Y B; Yerle, M; Liu, B

    2009-04-01

    Histone modifications (methylation and demethylation) regulate gene expression and play a role in cell proliferation and differentiation by their actions on chromatin structure. In this context, we studied the temporal expression profiles of genes acting on histone methylation and demethylation during skeletal muscle proliferation and differentiation. Quantitative real-time PCR was used to quantify the mRNA levels of CARM1, JARID1A, JMJD2A, LSD1, PRMT2, PRMT5, SMYD1, SMYD2, SMYD3, SETDB1, Suv39h2 and SUZ12 in foetal skeletal muscle. Our results showed that CARM1, JARID1A, JMJD2A, SMYD1 and SMYD2 were differentially expressed in embryonic muscles of 33 days post-conception (dpc), 65 dpc and 90 dpc. These 12 genes were mapped to porcine chromosomes (SSC) 2q21-24, 5q25, 6q35, 6q12-21, 6p15, 7q21, 3q21-27, 9q26, 10p16, 4q15-16, 10q14-16 and 12p12 respectively. Taking into account the reported QTL mapping results, gene expression analysis and radiation hybrid mapping results, these results suggest that five genes (CARM1, JARID1A, JMJD2A, SMYD1 and SMYD2) could be good candidate genes for growth and backfat thickness traits.

  3. Duration of transport and holding in lairage at constant postprandial delay to slaughter--effects on fatty liver and breast muscle quality in mule ducks.

    PubMed

    Fernandez, X; Bouillier-Oudot, M; Molette, C; Bernadet, M D; Manse, H

    2011-10-01

    The present study was designed to evaluate the effect of preslaughter transport (30 vs. 150 min) and holding of mule ducks in lairage in their transport crates (15 vs. 120 min) on the quality of the meat and fatty liver. A total of 120 birds were allocated in a 2 × 2 factorial design with a constant postprandial delay to slaughter (8 h), to avoid the confounding between the effects of the experimental treatments and those of fasting duration. Under such conditions, extending the transport or holding duration did not induce a loss in preslaughter live weight or liver weight. Similarly, breast muscle glycogen stores were not affected by the treatments, nor was the kinetics of postmortem pH decline affected. The mechanical resistance of raw meat obtained by the compression test significantly increased with holding duration. The gross chemical composition of the livers did not differ significantly among the preslaughter treatments. Residual blood in the liver, as indicated by heme pigment concentration, was enhanced with a longer transport, but this effect was more pronounced after the longest holding duration, as shown by a significant interaction. This, however, did not significantly affect the incidence of appearance defects or the commercial grading of the livers. The percentage of fat loss during the cooking of canned livers was significantly reduced when the transport duration was increased. This effect could not be explained on the basis of the current knowledge for determining the technological quality of fatty liver. The identification of biological markers of liver quality is currently underway in our laboratory. Further investigations studying the differential expression of these biological markers according to preslaughter conditions would provide a better understanding of the effect of transport duration on liver processing yield.

  4. Enzymic determination of branched-chain amino acids and 2-oxoacids in rat tissues. Transfer of 2-oxoacids from skeletal muscle to liver in vivo.

    PubMed Central

    Livesey, G; Lund, P

    1980-01-01

    1. A procedure is described for the purification of leucine dehydrogenase (EC 1.4.1.9) from Bacillus subtilis. 2. The preparation is suitable for the quantitative assay of branched-chain amino acids and their 2-oxoacid analogues. 3. The content of total branched-chain 2-oxoacids in freeze-clamped liver, kidney, heart or mammary gland of fed rats is less than 5 nmol/g fresh wt. Higher amounts are present in skeletal muscle and arterial blood (25 +/- 4 nmol per g fresh wt., and 33 +/- 6 nmol per ml respectively; means +/- S.D. of 3 and 11 animals respectively). The values are not significantly affected by starvation for 24 h. 4. Arteriovenous difference measurements show that considerable amounts of branched-chain 2-oxoacids are released by skeletal muscle into the circulation and similar amounts are removed by the liver (about 1 mmol/24 h in a 400 g rat). PMID:6781474

  5. Characterization of the liver kinase B1-mouse protein-25 -Ste-20-related adaptor protein complex in adult mouse skeletal muscle

    PubMed Central

    Smith, Cody D.; Compton, Richard A.; Bowler, Joshua S.; Kemp, Jonathan T.; Sudweeks, Sterling N.; Thomson, David M.

    2011-01-01

    In liver, the AMP-activated protein kinase kinase (AMPKK) complex was identified as the association of liver kinase B1 (LKB1), mouse protein 25 (MO25α/β), and Ste-20-related adaptor protein (STRADα/β); however, this complex has yet to be characterized in skeletal muscle. We demonstrate the expression of the LKB1-MO25-STRAD complex in skeletal muscle, confirm the absence of mRNA splice variants, and report the relative mRNA expression levels of these proteins in control and muscle-specific LKB1 knockout (LKB1−/−) mouse muscle. LKB1 detection in untreated control and LKB1−/− muscle lysates revealed two protein bands (50 and 60 kDa), although only the heavier band was diminished in LKB1−/− samples [55 ± 2.5 and 13 ± 1.5 arbitrary units (AU) in control and LKB1−/−, respectively, P < 0.01], suggesting that LKB1 is not represented at 50 kDa, as previously cited. The 60-kDa LKB1 band was further confirmed following purification using polyethylene glycol (43 ± 5 and 8.4 ± 4 AU in control and LKB1−/−, respectively, P < 0.01) and ion-exchange fast protein liquid chromatography. Mass spectrometry confirmed LKB1 protein detection in the 60-kDa protein band, while none was detected in the 50-kDa band. Coimmunoprecipitation assays demonstrated LKB1-MO25-STRAD complex formation. Quantitative PCR revealed significantly reduced LKB1, MO25α, and STRADβ mRNA in LKB1−/− muscle. These findings demonstrate that the LKB1-MO25-STRAD complex is the principal AMPKK in skeletal muscle. PMID:21903876

  6. The effect of exercise training and water extract from propolis intake on the antioxidant enzymes activity of skeletal muscle and liver in rat

    PubMed Central

    Kwon, Tae Dong; Lee, Mong Woo; Kim, Ki Hoon

    2014-01-01

    [Purpose] In this study, the authors have intended to investigate the effects that the exercise training and the intake of the water extract from propolis have on the activity of antioxidant enzymes. [Methods] For this purpose, the exercise training (70% VO2max treadmill running exercise for 60min)of 5 times per week for six weeks and the intake (50mg/kg/day) of the water extract from propolis were performed by separating the experimental animals (SD rats, n=32) into CON(n=8) group, CON+Ex(n=8), PA(n=8), and PA+Ex(n=8). [Results] As a result, the following conclusions were obtained: The concentration of the blood glucose and insulin of the CON+Ex group and PA+Ex group which are the exercise parallel group were significantly decreased in comparison with the control group, whereas if comparing the glycogen concentration in skeletal muscle and liver tissue between the exercise parallel group and the CON group, the former showed significantly high value in comparison with the latter (p < .05). In the case of the activity of the antioxidant enzyme in the skeletal muscle and the liver tissue, the activities of SOD, GPX and CAT in the gastrocnemius muscle tissue of the experimental animals showed significantly high value in PA+Ex group in comparison with other experimental groups (p < .05). In addition, the SOD activity in the liver tissue showed that only PA+Ex group was significantly increased, whereas GDX activity showed significantly higher value in CON+Ex group and PA group than CON group (p < .05). However, the activity of CAT in the liver tissue showed that there is no difference between the experimental groups. As a result that measured the concentration of MDA in order to evaluate the damage level of the tissue by oxygen free radicals, the difference between the groups in the liver tissue was not shown, while it was shown that only PA+Ex group in the skeletal muscle tissue was significantly decreased in comparison with other experimental groups (p < .05

  7. Total mercury concentrations in liver and muscle of European whitefish (Coregonus lavaretus (L.)) in a subarctic lake - Assessing the factors driving year-round variation.

    PubMed

    Keva, Ossi; Hayden, Brian; Harrod, Chris; Kahilainen, Kimmo K

    2017-09-16

    Subarctic lakes are characterised by extreme seasonal variation in light and temperature which influences growth, maturation, condition and resource use of fishes. However, our understanding of how seasonal changes affect mercury concentrations of fishes is limited. We conducted a year-round study (3 ice-covered months, 3 open-water months) with open-water inter-annual aspect (3 years: samples from August/September), focusing on total mercury (THg) concentrations and ecological characteristics of a common freshwater fish, European whitefish (Coregonus lavaretus (L.)) from a subarctic lake. We measured THg concentrations from tissues with fast (liver, n = 164) and moderate (muscle, n = 225) turnover rates, providing information on THg dynamics over different temporal scales. In both tissues, lipid-corrected THg concentrations were highest in winter (liver: 1.70 ± 0.88 μg/g, muscle: 0.24 ± 0.05 μg/g) and lowest in summer (liver: 0.87 ± 0.72 μg/g, muscle: 0.19 ± 0.04 μg/g). THg concentrations increased in winter following the summer-autumn dietary shift to pelagic zooplankton and starvation after spawning. Whitefish THg concentrations decreased towards summer, and were associated with consumption of benthic macroinvertebrates and subsequent growth dilution. Mercury bioaccumulated in both tissues with age, both showing the strongest regression slopes in winter and lowest in summer. THg concentrations in liver and muscle tissue were correlated throughout the year, however the correlation was lowest in summer, indicating high metabolism during somatic growing season in summer and growth dilution. Multiple linear regression models explained 50% and 55% of the THg variation in liver and muscle both models dominated by seasonally-variable factors i.e. sexual maturity, δ(13)C, and condition factor. Seasonally varying bioaccumulation slopes and the higher level of intra-annual variation (21%) in whitefish THg concentration in muscle than the inter

  8. Effects of acute exercise on lipid content and dietary lipid uptake in liver and skeletal muscle of lean and diabetic rats.

    PubMed

    Janssens, Sharon; Jonkers, Richard A M; Groen, Albert K; Nicolay, Klaas; van Loon, Luc J C; Prompers, Jeanine J

    2015-11-15

    Insulin resistance is associated with ectopic lipid accumulation. Physical activity improves insulin sensitivity, but the impact of exercise on lipid handling in insulin-resistant tissues remains to be elucidated. The present study characterizes the effects of acute exercise on lipid content and dietary lipid partitioning in liver and skeletal muscle of lean and diabetic rats by use of magnetic resonance spectroscopy (MRS). After baseline measurements, rats were randomized to exercise or no-exercise groups. A subset of animals was subjected to MRS directly after 1 h of treadmill running for measurement of total intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) content (n=7 lean and diabetic rats). The other animals were administered 13C-labeled lipids orally after treadmill visit (with or without exercise) followed by MRS measurements after 4 and 24 h to determine the 13C enrichment of IHCL and IMCL (n=8 per group). Total IHCL and IMCL content were fivefold higher in diabetic vs. lean rats (P<0.001). Exercise did not significantly affect IHCL content but reduced IMCL by 25±7 and 33±4% in lean and diabetic rats (P<0.05), respectively. Uptake of dietary lipids in liver and muscle was 2.3-fold greater in diabetic vs. lean rats (P<0.05). Prior exercise did not significantly modulate dietary lipid uptake into muscle, but in liver of both lean and diabetic rats, lipid uptake was 44% reduced after acute exercise (P<0.05). In conclusion, IMCL but not IHCL represents a viable substrate source during exercise in both lean and diabetic rats, and exercise differentially affects dietary lipid uptake in muscle and liver.

  9. Acute heat stress and dietary methionine effects on IGF-I, GHR, and UCP mRNA expression in liver and muscle of quails.

    PubMed

    Del Vesco, A P; Gasparino, E; Zancanela, V; Grieser, D O; Guimarães, S E F; Nascimento, C S; Voltolini, D M; Constantin, J; Gasparin, F S

    2014-02-13

    This study evaluated the expression of insulin-like growth factor I (IGF-I), growth hormone receptor (GHR), and uncoupling protein (UCP) mRNA in muscle and liver of quails that were in thermal comfort or exposed to heat stress and that were fed diets with or without methionine supplementation. Meat quails were fed a diet that either met the nutritional demands for methionine (MS) or did not meet this demand (methionine-deficient diet, MD). The animals were either kept at a thermal comfort temperature (25°C) or exposed to heat stress (38°C for 24 h starting on the 6th day). RNA was extracted from liver and breast muscle, and cDNA was synthesized and amplified using quantitative reverse transcription-polymerase chain reaction. Animals that were fed the MS diet and remained at the thermal comfort temperature exhibited increased IGF-I mRNA expression in the liver (0.56 AU). The GHR mRNA expression in the liver and muscle was influenced by both the study variables. Animals receiving the MS diet showed higher GHR expression, while increased expression was observed in animals at the thermal comfort temperature. The UCP mRNA expression in the muscle was influenced by both methionine supplementation and heat stress. Higher expression was observed in animals that received the MD diet (2.29 vs 3.77 AU) and in animals kept in thermal comfort. Our results suggest that heat stress negatively affects the expression of growth-related genes and that methionine supplementation is necessary to appropriately maintain the levels of IGF-I, GHR, and UCP transcripts for animal metabolism.

  10. ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGF-Induced Proliferation of Vascular Smooth Muscle Cells

    NASA Astrophysics Data System (ADS)

    Huang, Xu; Xu, Meng-Qi; Zhang, Wei; Ma, Sai; Guo, Weisheng; Wang, Yabin; Zhang, Yan; Gou, Tiantian; Chen, Yundai; Liang, Xing-Jie; Cao, Feng

    2017-05-01

    The proliferation of vascular smooth muscle cells (VSMCs) is one of the key events during the progress of atherosclerosis. The activated liver X receptor (LXR) signalling pathway is demonstrated to inhibit platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation. Notably, following PDGF-BB stimulation, the expression of intercellular adhesion molecule-1 (ICAM-1) by VSMCs increases significantly. In this study, anti-ICAM-1 antibody-conjugated liposomes were fabricated for targeted delivery of a water-insoluble LXR agonist (T0901317) to inhibit VSMC proliferation. The liposomes were prepared by filming-rehydration method with uniform size distribution and considerable drug entrapment efficiency. The targeting effect of the anti-ICAM-T0901317 liposomes was evaluated by confocal laser scanning microscope (CLSM) and flow cytometry. Anti-ICAM-T0901317 liposomes showed significantly higher inhibition effect of VSMC proliferation than free T0901317 by CCk8 proliferation assays and BrdU staining. Western blot assay further confirmed that anti-ICAM-T0901317 liposomes inhibited retinoblastoma (Rb) phosphorylation and MCM6 expression. In conclusion, this study identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression.

  11. Functional Coupling of Human Microphysiology Systems: Intestine, Liver, Kidney Proximal Tubule, Blood-Brain Barrier and Skeletal Muscle

    PubMed Central

    Vernetti, Lawrence; Gough, Albert; Baetz, Nicholas; Blutt, Sarah; Broughman, James R.; Brown, Jacquelyn A.; Foulke-Abel, Jennifer; Hasan, Nesrin; In, Julie; Kelly, Edward; Kovbasnjuk, Olga; Repper, Jonathan; Senutovitch, Nina; Stabb, Janet; Yeung, Catherine; Zachos, Nick C.; Donowitz, Mark; Estes, Mary; Himmelfarb, Jonathan; Truskey, George; Wikswo, John P.; Taylor, D. Lansing

    2017-01-01

    Organ interactions resulting from drug, metabolite or xenobiotic transport between organs are key components of human metabolism that impact therapeutic action and toxic side effects. Preclinical animal testing often fails to predict adverse outcomes arising from sequential, multi-organ metabolism of drugs and xenobiotics. Human microphysiological systems (MPS) can model these interactions and are predicted to dramatically improve the efficiency of the drug development process. In this study, five human MPS models were evaluated for functional coupling, defined as the determination of organ interactions via an in vivo-like sequential, organ-to-organ transfer of media. MPS models representing the major absorption, metabolism and clearance organs (the jejunum, liver and kidney) were evaluated, along with skeletal muscle and neurovascular models. Three compounds were evaluated for organ-specific processing: terfenadine for pharmacokinetics (PK) and toxicity; trimethylamine (TMA) as a potentially toxic microbiome metabolite; and vitamin D3. We show that the organ-specific processing of these compounds was consistent with clinical data, and discovered that trimethylamine-N-oxide (TMAO) crosses the blood-brain barrier. These studies demonstrate the potential of human MPS for multi-organ toxicity and absorption, distribution, metabolism and excretion (ADME), provide guidance for physically coupling MPS, and offer an approach to coupling MPS with distinct media and perfusion requirements. PMID:28176881

  12. Mercury in liver, kidney, feather and muscle of seabirds from major wetlands of the Caspian Sea, Iran.

    PubMed

    Aazami, J; Esmaili-Sari, A; Bahramifar, N; Ghasempouri, M; Savabieasfahani, M

    2011-06-01

    Concentration of mercury in tissues of the great cormorant (n = 18), mallard (n = 18), and coot (n = 15) of the Caspian Sea were determined. Liver mercury in the great cormorant, mallard, and coot were (5.7 ± 0.91; 0.3 ± 0.02; 0.09 ± 0.02). Kidney levels were (3.6 ± 2.24; 0.26 ± 0.03; 0.08 ± 0.02); feather (8.7 ± 0.8; 1.04 ± 0.16; 0.23 ± 0.15) and muscle were (2.26 ± 2.04; 0.11 ± 0.01; 0.03 ± 0.02) respectively. Mercury Tolerable Daily Intake limit is set at 5 μg g(-1). But even at levels that are currently considered "tolerable", mercury poisoning can occur in children and young who consume polluted game meat regularly.

  13. Sulfur mustard causes oxidative stress and depletion of antioxidants in muscles, livers, and kidneys of Wistar rats.

    PubMed

    Pohanka, Miroslav; Stetina, Rudolf; Svobodova, Hana; Ruttkay-Nedecky, Branislav; Jilkova, Martina; Sochor, Jiri; Sobotka, Jakub; Adam, Vojtech; Kizek, Rene

    2013-07-01

    Sulfur mustard (SM) is a chemical warfare agent with cytotoxic effect and a tight link to oxidative stress (OS). Depletion of antioxidants is considered as a cause of detrimental consequence and belongs to the important steps leading to cell death. The oxidative injury appearing after SM exposure is not well understood. Nevertheless, identification of the pathological processes would be a good opportunity to establish an efficient therapy. Here, we focused our effort on an estimation of reactive oxygen species homeostasis and apoptotic processes in Wistar rats exposed to 0-160 mg/kg of SM. We assayed antioxidant activity, thiobarbituric acid reactive substances, reduced glutathione/oxidized glutathione, metallothionein, glutathione reductase, glutathione peroxidase, glutathione S-transferase, caspase 3, and glucose in the livers, kidneys, and muscles of the animals. Significant OS, depletion of low-molecular-mass antioxidants, increase in caspase activity, and some other processes related to SM action were determined. Moreover, we infer a principal role of OS in the tested organs.

  14. Perfluoroalkyl sulfonates and carboxylic acids in liver, muscle and adipose tissues of black-footed albatross (Phoebastria nigripes) from Midway Island, North Pacific Ocean.

    PubMed

    Chu, Shaogang; Wang, Jun; Leong, Gladys; Woodward, Lee Ann; Letcher, Robert J; Li, Qing X

    2015-11-01

    The Great Pacific Garbage Patch (GPGP) is a gyre of marine plastic debris in the North Pacific Ocean, and nearby is Midway Atoll which is a focal point for ecological damage. This study investigated 13 C4-C16 perfluorinated carboxylic acids (PFCAs), four (C4, C6, C8 and C10) perfluorinated sulfonates and perfluoro-4-ethylcyclohexane sulfonate [collectively perfluoroalkyl acids (PFAAs)] in black-footed albatross tissues (collected in 2011) from Midway Atoll. Of the 18 PFCAs and PFSAs monitored, most were detectable in the liver, muscle and adipose tissues. The concentrations of PFCAs and PFSAs were higher than those in most seabirds from the arctic environment, but lower than those in most of fish-eating water birds collected in the U.S. mainland. The concentrations of the PFAAs in the albatross livers were 7-fold higher than those in Laysan albatross liver samples from the same location reported in 1994. The concentration ranges of PFOS were 22.91-70.48, 3.01-6.59 and 0.53-8.35 ng g(-1) wet weight (ww), respectively, in the liver, muscle and adipose. In the liver samples PFOS was dominant, followed by longer chain PFUdA (8.04-18.70 ng g(-1) ww), PFTrDA, and then PFNA, PFDA and PFDoA. Short chain PFBA, PFPeA, PFBS and PFODA were below limit of quantification. C8-C13 PFCAs showed much higher composition compared to those found in other wildlife where PFOS typically predominated. The concentrations of PFUdA in all 8 individual albatross muscle samples were even higher than those of PFOS. This phenomenon may be attributable to GPGP as a pollution source as well as PFAA physicochemical properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Perfluoroalkyl Sulfonates and Carboxylic Acids in Liver, Muscle and Adipose Tissues of Black-Footed Albatross (Phoebastria nigripes) from Midway Island, North Pacific Ocean

    PubMed Central

    Chu, Shaogang; Wang, Jun; Leong, Gladys; Woodward, Lee Ann; Letcher, Robert J.; Li, Qing X.

    2015-01-01

    The Great Pacific Garbage Patch (GPGP) is a gyre of marine plastic debris in the North Pacific Ocean, and nearby is Midway Atoll which is a focal point for ecological damage. This study investigated 13 C4-C16 perfluorinated carboxylic acids (PFCAs), four (C4, C6, C8 and C10) perfluorinated sulfonates and perfluoro-4-ethylcyclohexane sulfonate [collectively perfluoroalkyl acids (PFAAs)] in black-footed albatross tissues (collected in 2011) from Midway Atoll. Of the 18 PFCAs and PFSAs monitored, most were detectable in the liver, muscle and adipose tissues. The concentrations of PFCAs and PFSAs were higher than those in most seabirds from the arctic environment, but lower than those in most of fish-eating water birds collected in the U.S. mainland. The concentrations of the PFAAs in the albatross livers were 7-fold higher than those in Laysan albatross liver samples from the same location reported in 1994. The concentration ranges of PFOS were 22.91-70.48, 3.01-6.59 and 0.53-8.35 ng g-1 wet weight (ww), respectively, in the liver, muscle and adipose. In the liver samples PFOS was dominant, followed by longer chain PFUdA (8.04-18.70 ng g-1 ww), PFTrDA, and then PFNA, PFDA and PFDoA. Short chain PFBA, PFPeA, PFBS and C16 PFODA were below limit of quantification. C8-C13 PFCAs showed much higher composition compared to those found in other wildlife where PFOS typically predominated. The concentrations of PFUdA in all 8 individual albatross muscle samples were even higher than those of PFOS. This phenomenon may be attributable to GPGP as a pollution source as well as PFAA physicochemical properties. PMID:26037817

  16. Long term betaine supplementation regulates genes involved in lipid and cholesterol metabolism of two muscles from an obese pig breed.

    PubMed

    Albuquerque, A; Neves, José A; Redondeiro, M; Laranjo, M; Félix, M R; Freitas, Amadeu; Tirapicos, José L; Martins, José M

    2017-02-01

    This study evaluates the effects of betaine supplementation (1gkg(-1) for 20weeks) on the regulation of genes involved in lipid and cholesterol metabolism of Longissimus lumborum and Biceps femoris from obese Alentejano pigs. Betaine supplementation led to an increase in total cholesterol in both muscles, complementing results previously published indicating a significant increase on the intramuscular lipid content. The expression of twelve genes involved in lipogenesis, lipolysis/FA oxidation, FA transport, and cholesterol metabolism, as well as two transcription factors were also evaluated. Genes related to lipid and cholesterol synthesis plus FA transport were consistently up-regulated in both muscles of betaine fed pigs. On the other hand, genes related to lipolysis/FA oxidation were not affected or down-regulated by betaine supplementation. Our data suggest that the underlying mechanism regulating IMF and cholesterol accumulation in Alentejano pigs supplemented with betaine is associated with the up-regulation of genes involved in lipid synthesis, FA transport, and cholesterol synthesis.

  17. Molecular Basis of Ion Channels and Receptors Involved in Nerve Excitation, Synaptic Transmission and Muscle Contraction

    DTIC Science & Technology

    1993-12-20

    shows the effect of minoxidil sulphate on CFTR Cl currents; similar results were obtained with BRL 38227 and diazoxide. As was observed for the...dependent; halt-maximal inhibition occurred at about 40 l±M minoxidil sulphate, 50 pM BRI. 38227, and 250 p.M diazoxide. This effect was weaker than...their stimulation of K-ATP channels in vascular smooth muscle."’ 280 ANNALS NEW YORK ACADEMY OF SCIENCES +50 mV -90 mV A ~Bi cAMP cAMP + minoxidil

  18. Fatty-acid profiles of white muscle and liver in stream-maturing steelhead trout Oncorhynchus mykiss from early migration to kelt emigration

    USGS Publications Warehouse

    Penney, Zachary L.; Moffitt, Christine M.

    2015-01-01

    The profiles of specific fatty acids (FA) in white muscle and liver of fasting steelhead troutOncorhynchus mykiss were evaluated at three periods during their prespawning migration and at kelt emigration in the Snake–Columbia River of Washington, Oregon and Idaho, to improve the understanding of energy change. Twenty-seven FAs were identified; depletion of 10 of these was positively correlated in liver and white muscle of prespawning O. mykiss. To observe relative changes in FA content more accurately over sampling intervals, the lipid fraction of tissues was used to normalize the quantity of individual FA to an equivalent tissue wet mass. Saturated and monounsaturated FAs were depleted between upstream migration in September and kelt emigration in June, whereas polyunsaturated FAs were more conserved. Liver was depleted of FAs more rapidly than muscle. Three FAs were detected across all sampling intervals: 16:0, 18:1 and 22:6n3, which are probably structurally important to membranes. When structurally important FAs of O. mykiss are depleted to provide energy, physiological performance and survival may be affected.

  19. The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men

    PubMed Central

    Browning, Jeffrey D.; Baxter, Jeannie; Satapati, Santhosh; Burgess, Shawn C.

    2012-01-01

    Fasting promotes triglyceride (TG) accumulation in lean tissues of some animals, but the effect in humans is unknown. Additionally, fasting lipolysis is sexually dimorphic in humans, suggesting that lean tissue TG accumulation and metabolism may differ between women and men. This study investigated lean tissue TG content and metabolism in women and men during extended fasting. Liver and muscle TG content were measured by magnetic resonance spectroscopy during a 48-h fast in healthy men and women. Whole-body and hepatic carbohydrate, lipid, and energy metabolism were also evaluated using biochemical, calorimetric, and stable isotope tracer techniques. As expected, postabsorptive plasma fatty acids (FAs) were higher in women than in men but increased more rapidly in men with the onset of early starvation. Concurrently, sexual dimorphism was apparent in lean tissue TG accumulation during the fast, occurring in livers of men but in muscles of women. Despite differences in lean tissue TG distribution, men and women had identical fasting responses in whole-body and hepatic glucose and oxidative metabolism. In conclusion, TG accumulated in livers of men but in muscles of women during extended fasting. This sexual dimorphism was related to differential fasting plasma FA concentrations but not to whole body or hepatic utilization of this substrate. PMID:22140269

  20. Mineral composition and toxic element levels of muscle, liver and kidney of intensive (Swedish Landrace) and extensive (Mangulica) pigs from Serbia.

    PubMed

    Nikolic, Dragica; Djinovic-Stojanovic, Jasna; Jankovic, Sasa; Stanisic, Nikola; Radovic, Cedomir; Pezo, Lato; Lausevic, Mila

    2017-03-27

    Mineral composition (Fe, Zn, Cu, Mn, Se, Cr, Co, Ni, Na, K, Mg, Ca) and toxic element levels (Cd, Pb, Hg, As) of soil, feed and tissue (muscle, liver and kidney) from intensive (Swedish Landrace, housed indoors, fed a known diet, 4 years) and extensive (Mangulica, free-roaming, non-specified diet, 7-8 months) pigs was determined by inductively coupled plasma mass spectrometry (ICP-MS). Controlled nutrition produced pigs with higher concentrations of most minerals (muscle: Mn, Se, K, Mg; liver: Zn, Cu, Mn, Se, Cr, Ca; kidney: Zn, Cu, Mn, Se, K, Mg), but for Fe, the opposite trend was found. Long-term free-ranging pigs have higher risk of contamination by toxic elements (Cd exceeded the maximum residue level in kidney). Principal Component Analysis and Cluster Analysis were used to assess the effect of different pig breed/lifestyle (pig type) on element composition of muscle, liver and kidney of pigs. Multivariate data analysis showed good discriminating capabilities.

  1. Accumulation of Copper in Gill, Liver, Spleen, Kidney and Muscle Tissues of Clarias gariepinus Exposed to the Metal Singly and in Mixture with Chitosan.

    PubMed

    Tunçsoy, Mustafa; Duran, Servet; Ay, Özcan; Cicik, Bedii; Erdem, Cahit

    2016-10-01

    Accumulation of copper (Cu), applied singly and in mixture with chitosan (CT), in gill, liver, spleen, kidney and muscle tissues of Clarias gariepinus was studied after exposing the fish to no Cu (control), 5 ppm Cu, 5 ppm Cu + 75 ppm CT mixture over 1, 7 and 15 days. Metal levels in tissues were determined using an ICP-AES spectrophotometer. No mortality was observed during the experiments. Highest accumulation of Cu was observed in liver while lowest accumulation was observed in muscle tissue. Exposure to Cu-CT mixture decreased Cu accumulation in liver at all exposure periods and in kidney on the 15th day compared to Cu alone. Exposure to Cu alone and Cu-CT mixture had no effect on Cu accumulation in spleen or muscle tissue. Copper accumulation increased in gill tissue compared to control when exposed to Cu alone at all exposure periods, and exposure to the Cu-CT mixture significantly increased Cu accumulation in this tissue at all exposure periods compared to Cu alone.

  2. The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men.

    PubMed

    Browning, Jeffrey D; Baxter, Jeannie; Satapati, Santhosh; Burgess, Shawn C

    2012-03-01

    Fasting promotes triglyceride (TG) accumulation in lean tissues of some animals, but the effect in humans is unknown. Additionally, fasting lipolysis is sexually dimorphic in humans, suggesting that lean tissue TG accumulation and metabolism may differ between women and men. This study investigated lean tissue TG content and metabolism in women and men during extended fasting. Liver and muscle TG content were measured by magnetic resonance spectroscopy during a 48-h fast in healthy men and women. Whole-body and hepatic carbohydrate, lipid, and energy metabolism were also evaluated using biochemical, calorimetric, and stable isotope tracer techniques. As expected, postabsorptive plasma fatty acids (FAs) were higher in women than in men but increased more rapidly in men with the onset of early starvation. Concurrently, sexual dimorphism was apparent in lean tissue TG accumulation during the fast, occurring in livers of men but in muscles of women. Despite differences in lean tissue TG distribution, men and women had identical fasting responses in whole-body and hepatic glucose and oxidative metabolism. In conclusion, TG accumulated in livers of men but in muscles of women during extended fasting. This sexual dimorphism was related to differential fasting plasma FA concentrations but not to whole body or hepatic utilization of this substrate.

  3. GLUT-4 translocation in skeletal muscle studied with a cell-free assay: involvement of phospholipase D.

    PubMed

    Kristiansen, S; Nielsen, J N; Bourgoin, S; Klip, A; Franco, M; Richter, E A

    2001-09-01

    GLUT-4-containing membranes immunoprecipitated from insulin-stimulated rat skeletal muscle produce the phospholipase D (PLD) product phosphatidic acid. In vitro stimulation of PLD in crude membrane with ammonium sulfate (5 mM) resulted in transfer of GLUT-4 (3.0-fold vs. control) as well as transferrin receptor proteins from large to small membrane structures. The in vitro GLUT-4 transfer could be blocked by neomycin (a PLD inhibitor), and neomycin also reduced insulin-stimulated glucose transport in intact incubated soleus muscles. Furthermore, protein kinase B(beta) (PKB(beta)) was found to associate with the GLUT-4 protein and was transferred to small vesicles in response to ammonium sulfate in vitro. Finally, addition of cytosolic proteins, prepared from basal skeletal muscle, and GTP nucleotides to an enriched GLUT-4 membrane fraction resulted in in vitro transfer of GLUT-4 to small membranes (6.8-fold vs. unstimulated control). The cytosol and nucleotide-induced GLUT-4 transfer could be blocked by neomycin and N-ethylmaleimide. In conclusion, we have developed a cell-free assay that demonstrates in vitro GLUT-4 transfer. This transfer may suggest release of GLUT-4-containing vesicles from donor GLUT-4 membranes involving PLD activity and binding of PKB(beta) to GLUT-4.

  4. Drosophila Importin-α2 Is Involved in Synapse, Axon and Muscle Development

    PubMed Central

    Mosca, Timothy J.; Schwarz, Thomas L.

    2010-01-01

    Nuclear import is required for communication between the cytoplasm and the nucleus and to enact lasting changes in gene transcription following stimuli. Binding to an Importin-α molecule in the cytoplasm is often required to mediate nuclear entry of a signaling protein. As multiple isoforms of Importin-α exist, some may be responsible for the entry of distinct cargoes rather than general nuclear import. Indeed, in neuronal systems, Importin-α isoforms can mediate very specific processes such as axonal tiling and communication of an injury signal. To study nuclear import during development, we examined the expression and function of Importin-α2 in Drosophila melanogaster. We found that Importin-α2 was expressed in the nervous system where it was required for normal active zone density at the NMJ and axonal commissure formation in the central nervous system. Other aspects of synaptic morphology at the NMJ and the localization of other synaptic markers appeared normal in importin-α2 mutants. Importin-α2 also functioned in development of the body wall musculature. Mutants in importin-α2 exhibited errors in muscle patterning and organization that could be alleviated by restoring muscle expression of Importin-α2. Thus, Importin-α2 is needed for some processes in the development of both the nervous system and the larval musculature. PMID:21151903

  5. Embryonic liver fordin is involved in glucose glycolysis of hepatic stellate cell by regulating PI3K/Akt signaling.

    PubMed

    Tu, Wei; Ye, Jin; Wang, Zhi-Jun

    2016-10-14

    To investigate the role of embryonic liver fordin (ELF) in liver fibrosis by regulating hepatic stellate cells (HSCs) glucose glycolysis. The expression of ELF and the glucose glycolysis-related proteins were evaluated in activated HSCs. siRNA was used to silence ELF expression in activated HSCs in vitro and the subsequent changes in PI3K/Akt signaling and glucose glycolysis-related proteins were observed. The expression of ELF increased remarkably in HSCs of the fibrosis mouse model and HSCs that were cultured for 3 wk in vitro. Glucose glycolysis-relat