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Sample records for muscle brain liver

  1. Developmental changes of protein, RNA, DNA, lipid, and glycogen in the liver, skeletal muscle, and brain of the piglet

    International Nuclear Information System (INIS)

    Hakkarainen, J.

    1975-01-01

    A scheme for the sequential quantitative separation and determination of protein, RNA, DNA, lipid, and glycogen from rat-liver homogenate is modified for application to frozen tissues of the piglet. The biochemical methods, including the biuret method, used in the present investigation are described and thoroughly checked. The effects of freezing and storage on the recovery of major tissue constituents are recorded. The modified scheme is applied to the determination of protein, RNA, DNA, lipid, and glycogen in the liver, skeletal muscle, and brain of the developing piglet. Developmental changes for these major tissue constituents, including the biuret protein, are described with special reference to protein synthesis and physiology of growth at the cellular level from 45 days of foetal age to 35-42 days of postnatal age for liver and skeletal muscle, and from birth to 31-40 days of postnatal age for the cerebrum and cerebellum. The uniformly labelled amino acid, 14 C-L-leucine, is used to study protein synthesis. Developmental patterns of labelling of protein and lipid in the liver, skeletal muscle, cerebrum, and cerebellum of the piglet from birth up to the age of two weeks are described. The results of the methodological, developmental, and experimental studies are thoroughly discussed in the light of the relevant literature and compared with those obtained in developmental and experimental studies on rats and other mammal species. (author)

  2. In vivo field dependence of proton relaxation times in human brain, liver and skeletal muscle: a multicenter study

    DEFF Research Database (Denmark)

    Henriksen, O; de Certaines, J D; Spisni, A

    1993-01-01

    and MRS, the in vivo field dispersion of T1 and T2 has been measured in order to evaluate whether ex vivo data are representative for the in vivo situation. Brain, skeletal muscle, and liver of healthy human volunteers were studied. Fifteen MR units with a field strength ranging from 0.08 T to 1.5 T took......T1 and T2 relaxation times are fundamental parameters for signal contrast behaviour in MRI. A number of ex vivo relaxometry studies have dealt with the magnetic field dispersion of T1. By means of multicenter study within the frame of the COMAC BME Concerted Action on Tissue Characterization by MRI......, whereas no significant variations were seen for T2. Our in vivo data were generally in reasonable agreement with proposed models based on ex vivo measurements....

  3. Determination of prodrug treosulfan and its biologically active monoepoxide in rat plasma, liver, lungs, kidneys, muscle, and brain by HPLC-ESI-MS/MS method.

    Science.gov (United States)

    Romański, Michał; Kasprzyk, Anna; Teżyk, Artur; Widerowska, Agnieszka; Żaba, Czesław; Główka, Franciszek

    2017-06-05

    A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance. In this paper, a selective and rapid HPLC-ESI-MS/MS method was elaborated and validated for the studies of disposition of TREO and S,S-EBDM in rat plasma, liver, lungs, kidneys, muscle, and brain. The two analytes and codeine, internal standard (IS), were isolated from 50μL of plasma and 100μL of supernatants of the tissues homogenates using ultrafiltration Amicon vials. Chromatographic resolution was accomplished on C18 column with isocratic elution. The limits of quantitation of TREO and S,S-EBDM in the studied matrices ranged from 0.11 to 0.93μM. The HPLC-MS/MS method was adequately precise and accurate within and between runs. The IS-normalized matrix effect differed among the tissues and was the most pronounced in a liver homogenate supernatant (approximately 0.55 for TREO and 0.35 for S,S-EBDM). Stability of the analytes in experimental samples was also established. The validated method for the first time enabled determination of TREO and S,S-EBDM in the six life-important tissues in rats following administration of the prodrug. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Liver and muscle protein metabolism in cachexia

    NARCIS (Netherlands)

    Peters, J.A.C.

    2009-01-01

    Up to 50% of cancer patients suffer from progressive weight loss (cachexia). Cachexia is induced by proinflammatory mediators (cytokines), induced by the tumor’s presence. These cytokines induce so-called acute phase protein synthesis by the liver, followed by skeletal muscle protein breakdown.

  5. [Brain oedema and acute liver failure].

    Science.gov (United States)

    Spahr, L

    2003-04-01

    Brain oedema leading to intracranial hypertension occurs in a significant proportion of patients with acute liver failure in whom it is a leading cause of death. Although precise pathogenic mechanisms associated to this severe complication remain incompletely understood, increasing evidence points to gut-derived neurotoxins including ammonia as key mediators in cerebral osmotic and perfusion disturbances. The management of brain oedema and intracranial hypertension requires a multidisciplinar approach in a center where liver transplantation is available, as this option is the only treatment modality that provides improvement in outcome. This article reviews the most common causes of acute liver failure and the standard of supportive care management, and describes future potential therapeutic aspects of brain oedema and intracranial hypertension.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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

  7. Muscle and liver glycogen, protein, and triglyceride in the rat

    DEFF Research Database (Denmark)

    Richter, Erik; Sonne, Bente; Joensen Mikines, Kari

    1984-01-01

    in skeletal muscle was accompanied by increased breakdown of triglyceride and/or protein. Thus, the effect of exhausting swimming and of running on concentrations of glycogen, protein, and triglyceride in skeletal muscle and liver were studied in rats with and without deficiencies of the sympatho......-adrenal system. In control rats, both swimming and running decreased the concentration of glycogen in fast-twitch red and slow-twitch red muscle whereas concentrations of protein and triglyceride did not decrease. In the liver, swimming depleted glycogen stores but protein and triglyceride concentrations did...... not decrease. In exercising rats, muscle glycogen breakdown was impaired by adrenodemedullation and restored by infusion of epinephrine. However, impaired glycogen breakdown during exercise was not accompanied by a significant net breakdown of protein or triglyceride. Surgical sympathectomy of the muscles did...

  8. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard

    2013-01-01

    -specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...... of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including...

  9. Liver, but not muscle, has an entrainable metabolic memory.

    Directory of Open Access Journals (Sweden)

    Sheng-Song Chen

    Full Text Available 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.

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

    Science.gov (United States)

    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%, (Pglycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (PGlycogen synthase activity was 12% higher (Pglycogen branching enzyme activity was 70% lower (Pglycogen breakdown, glycogen phosphorylase, had 62% lower activity (Pglycogen debranching enzyme expression was 50% higher (Pglycogen (Pglycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; Pglycogen but reduced amounts of liver glycogen. PMID:24626262

  11. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

    Directory of Open Access Journals (Sweden)

    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxiatolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  12. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

    Directory of Open Access Journals (Sweden)

    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxia-tolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  13. Brain MRI changes in chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Skehan, S. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Norris, S. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Hegarty, J. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Owens, A. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); MacErlaine, D. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland)

    1997-08-01

    Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs.

  14. Loss of brain function - liver disease

    Science.gov (United States)

    Hepatic coma; Encephalopathy - hepatic; Hepatic encephalopathy; Portasystemic encephalopathy ... 2017:417-421. Nevah MI, Fallon MB. Hepatic encephalopathy, hepatorenal ... of liver disease. In: Feldman M, Friedman LS, Brandt LJ, ...

  15. Brain MRI changes in chronic liver disease

    International Nuclear Information System (INIS)

    Skehan, S.; Norris, S.; Hegarty, J.; Owens, A.; MacErlaine, D.

    1997-01-01

    Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs

  16. Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA

    Science.gov (United States)

    Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

    2015-01-01

    A number of contaminants affect fish health, including mercury and selenium, and the selenium: mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium: mercury molar ratios by tissues. Total mercury averaged 0.32 ± 0.02 ppm wet weight in edible muscle and 0.09 ± 0.01 ppm in brain. Selenium concentration averaged 0.37 ± 0.03 in muscle and 0.36 ± 0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium: mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium: mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. PMID:23202378

  17. Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kato, Ken-Ichiro; Takeshita, Yumie; Misu, Hirofumi; Zen, Yoh; Kaneko, Shuichi; Takamura, Toshinari

    2015-03-01

    To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease. Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method. The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = -0.45, P hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = -0.22, P steatosis and metabolic clearance rate (coefficient = -0.62, P = 0.059). Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.

  18. Skeletal Muscle and Liver Lipidomics and the Regulation of FAT/CD36

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting

    induced obesity in mice, we observed an increased muscle and liver lipid content, analyzed by mass spectrometry, concomitant with decreased glucose tolerance. We observed that treadmill exercise-training in high-fat fed mice resulted in a reduction in the lipid content in the liver, but not in muscle...... that the current worldwide obesity epidemic has resulted in the increased prevalence of “metabolic disease clusters”, including type 2 diabetes, fatty liver disease and dyslipidemia. Excessive plasma lipids can result in the accumulation of lipid metabolites at ectopic sites including skeletal muscle and liver...... during isolated muscle contractions. On the contrary, previous observations suggest that a permanent relocation of FAT/CD36 protein to the sarcolemma induces intracellular lipid accumulation, resulting in insulin resistance. Therefore, FAT/CD36 has been linked to insulin resistance. Whether increased FAT...

  19. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Somik [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yin, Hongshan [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Cardiovascular Medicine, Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei (China); Nam, Deokhwa [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Li, Yong [Department of Pediatric Surgery, Center for Stem Cell Research and Regenerative Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Ma, Ke, E-mail: kma@houstonmethodist.org [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States)

    2015-02-01

    Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1{sup −/−} mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation.

  20. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

    International Nuclear Information System (INIS)

    Chatterjee, Somik; Yin, Hongshan; Nam, Deokhwa; Li, Yong; Ma, Ke

    2015-01-01

    Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1 −/− mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation

  1. A brain-liver circuit regulates glucose homeostasis.

    Science.gov (United States)

    Pocai, Alessandro; Obici, Silvana; Schwartz, Gary J; Rossetti, Luciano

    2005-01-01

    Increased glucose production (GP) is the major determinant of fasting hyperglycemia in diabetes mellitus. Previous studies suggested that lipid metabolism within specific hypothalamic nuclei is a biochemical sensor for nutrient availability that exerts negative feedback on GP. Here we show that central inhibition of fat oxidation leads to selective activation of brainstem neurons within the nucleus of the solitary tract and the dorsal motor nucleus of the vagus and markedly decreases liver gluconeogenesis, expression of gluconeogenic enzymes, and GP. These effects require central activation of ATP-dependent potassium channels (K(ATP)) and descending fibers within the hepatic branch of the vagus nerve. Thus, hypothalamic lipid sensing potently modulates glucose metabolism via neural circuitry that requires the activation of K(ATP) and selective brainstem neurons and intact vagal input to the liver. This crosstalk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to hyperglycemia.

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

    Science.gov (United States)

    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. Copyright © 2016 the American Physiological Society.

  3. Content of copper, zinc, lead, cadmium and mercury in muscle, liver and kidney of Finnish cattle

    Energy Technology Data Exchange (ETDEWEB)

    Stabel-Taucher, R; Nurmi, E; Karppanen, E

    1975-01-01

    A total of 120 normal slaughter cows were analyzed with respect to Cu, Zn, Pb, Cd and Hg in muscle, liver and kidneys. The cows originated from 6 different slaughter-houses throughout the country. Imported cow livers, were also analyzed for comparison with the Finnish material. The Cu content in the Finnish animals turned out to be relatively low. The imported samples had even lower contents. There seemed to be no correlation between the Cu contents in muscle, liver and kidneys. Statistical tests established that the mean Cu content in livers from Oulu was significantly higher than most of the others at the 5% level. The Zn determinations revealed the highest amounts in the muscle. No correlation between the contents in muscle, liver and kidneys was shown. The animals from Seinaejoki had the highest Zn contents, significantly different from most of the others. The imported livers did not differ much from the domestic ones with regards to the Zn content. The same was true for the Pb content. The correlation coefficients of Pb in muscles, liver and kidneys were low. The animals from Kouvola contained the highest amounts of Pb, and the mean Pb content of these animals' kidneys was significantly different from all the others. The Cd content was highest in the animals from Turku. A good correlation was observed between the Cd contents in liver and kidneys. The Cd content of the imported livers was of the same order as that of the Finnish ones. No correlation was found between the Zn, Pb and Cd contents. The amounts of Hg in Finnish cattle were very low, especially so in animals from the North of Finland. The Hg content of the imported samples was of the same order as the figures recorded from the South of Finland. 24 references, 5 tables.

  4. Skeletal Muscle Derived IL-6 in Liver and Adipose Tissue Metabolism

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

    Summary Physical activity can lead to metabolic disease and treatment of several metabolic diseases include exercise training. Skeletal muscle has, due to its central role in glucose and fat metabolism at rest and during exercise been studied in detail with regard to exercise training. The role...... of both liver and adipose tissue regulation in whole body metabolism has come in to focus and it has been shown that both tissues are subject to exercise training-induced adaptations. However, the contribution of endocrine factors to the regulation of exercise training-induced adaptations in liver...... and adipose tissue metabolism is unknown. It has been suggested that myokines, such as IL-6, released from skeletal muscle affects liver and adipose tissue and are involved in the regulation of exercise training adaptations. Thus, the aim of this thesis was to investigate the role of skeletal muscle derived...

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

    Science.gov (United States)

    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.

  6. 1H MR spectroscopy of skeletal muscle, liver and bone marrow

    International Nuclear Information System (INIS)

    Machann, Juergen; Stefan, Norbert; Schick, Fritz

    2008-01-01

    Proton magnetic resonance spectroscopy ( 1 H MRS) offers interesting metabolic information even from organs outside the brain. In the first part, applications in skeletal muscle for determination of intramyocellular lipids (IMCL), which are involved in the pathogenesis of insulin resistance, are described. Peculiarities of spectral pattern are discussed and studies for short-term regulation of IMCL, as dietary intervention, exercise and fasting are presented. The second part deals with quantification of small amounts of lipids in the liver (hepatic lipids, HL), which is also of increasing interest in the field of diabetes research. Recommendations for correct assessment of spectra in this 'moving organ' are given and the importance of HL is described by examples of a cohort at increased risk for type 2 diabetes. Regulation of HL is described on the basis of a few studies. The third part concentrates on spectral characterization of bone marrow. Peripheral bone marrow of adults consists mainly of fat, while central marrow regions in the pelvis, spinal column and breast bone (and the peripheral bone marrow of children as well) contribute to blood formation and show a variable composition of adipocytes (fat cells), interstitial fluid and water containing precursor cells for erythrocytes, leucocytes and thrombocytes. Adapted 1 H spectroscopic techniques allow a semi-quantitative analysis of bone marrow composition

  7. {sup 1}H MR spectroscopy of skeletal muscle, liver and bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Machann, Juergen [Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany)], E-mail: juergen.machann@med.uni-tuebingen.de; Stefan, Norbert [Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls University Tuebingen, 72076 Tuebingen (Germany); Schick, Fritz [Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany)

    2008-08-15

    Proton magnetic resonance spectroscopy ({sup 1}H MRS) offers interesting metabolic information even from organs outside the brain. In the first part, applications in skeletal muscle for determination of intramyocellular lipids (IMCL), which are involved in the pathogenesis of insulin resistance, are described. Peculiarities of spectral pattern are discussed and studies for short-term regulation of IMCL, as dietary intervention, exercise and fasting are presented. The second part deals with quantification of small amounts of lipids in the liver (hepatic lipids, HL), which is also of increasing interest in the field of diabetes research. Recommendations for correct assessment of spectra in this 'moving organ' are given and the importance of HL is described by examples of a cohort at increased risk for type 2 diabetes. Regulation of HL is described on the basis of a few studies. The third part concentrates on spectral characterization of bone marrow. Peripheral bone marrow of adults consists mainly of fat, while central marrow regions in the pelvis, spinal column and breast bone (and the peripheral bone marrow of children as well) contribute to blood formation and show a variable composition of adipocytes (fat cells), interstitial fluid and water containing precursor cells for erythrocytes, leucocytes and thrombocytes. Adapted {sup 1}H spectroscopic techniques allow a semi-quantitative analysis of bone marrow composition.

  8. Contractures and involuntary muscle overactivity in severe brain injury.

    Science.gov (United States)

    Pohl, Marcus; Mehrholz, Jan; Rockstroh, Günter; Rückriem, Stefan; Koch, Rainer

    2007-04-01

    The aim of the present study was to evaluate the association of contractures with an increase or reduction of non-spastic muscle overactivity due to severe cerebral damage. Forty-five patients with tetraparesis after severe cerebral damage were investigated. Three groups were defined based on the presence of spasticity (revealed as resistance to passive stretch (= hypertonia)), and the presence of contracture of the relevant knee joint: Group(s) (17 patients with hypertonia without contracture), Group(s+c) (20 patients with hypertonia and contracture), and Group(c) (eight patients without hypertonia and with contracture). In all groups spontaneous involuntary muscle activity was assessed continuously over a 12-hour period through isometric measurement of knee joint flexion torque. A mathematical algorithm differentiated an hourly muscle activity spectrum (PI(h)). The frequency of peaks (peaks(h)) from the activity spectrum was determined. We revealed that Group(s) had higher PI(h) and more frequent peaks(h) compared with Group(s+c) and Group(c) (p0.05). The presence of contractures was associated with lower involuntary muscle overactivity in terms of lower PI(h) and less frequent peaks(h), indicating that contractures may be associated with reduced non-spastic positive features of the upper motor neurone syndrome in patients with severe brain damage.

  9. Examination of liver and muscle glycogen and blood glucose levels ...

    African Journals Online (AJOL)

    Administrator

    2011-09-05

    Sep 5, 2011 ... changes in fish affect the conversion of liver glycogen into blood ... province, altitude 1248 m and surface area of 86 km2, 20 km in length 4.5 km in width ... alcohol (95% pure) were added, followed by boiling for a further 15 min. ..... water temperature on the blood glucose level of chub (Leuciscus cephalus ...

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

    Science.gov (United States)

    Fedorov, Vadim B; Goropashnaya, Anna V; Tøien, Øivind; 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.

  11. In vivo postprandial lipid partitioning in liver and muscle of diabetic rats is disturbed

    NARCIS (Netherlands)

    Prompers, J.J.; Jonkers, R.A.M.; Loon, van L.J.C.; Nicolay, K.

    2012-01-01

    Objective: To study in vivo lipid partitioning in insulin-resistant liver and muscle of diabetic rats using magnetic resonance spectroscopy (MRS). Methods: Four groups of n=6 male Zucker diabetic fatty rats were used for this study: obese, pre-diabetic fa/fa rats and lean, non-diabetic fa/+

  12. CADMIUM ACCUMULATION IN HORSE MUSCLE, LIVER AND KIDNEY SLAUGHTERED IN BARI

    Directory of Open Access Journals (Sweden)

    P. Pinto

    2013-02-01

    Full Text Available The occurrence of Cadmium was measured in the muscle, liver and kidneys of 220 horses, 120 Polish, 55 Spanish and 45 Italian, subdivided into age-group. The kidneys were found to be the most contaminated and the concentration reveals a situation which should be under investigation.

  13. Muscle and Liver Carbohydrates: Response to Military Task Performance by Women and Men

    Science.gov (United States)

    2000-10-01

    rapidly synthesize glycogen from three-carbon compounds generated by muscle metabolism and taken up by the liver ( gluconeogenesis ). 20 UNPUBLISHED DATA...49008 Glial cell line-derived neturotrophic factor (GDNF) is a recently discovered nerrotrophic factor that afflets peripheral motor neurons . Increased

  14. Brain Aquaporin-4 in Experimental Acute Liver Failure

    Science.gov (United States)

    Rama Rao, Kakulavarapu V.; Jayakumar, Arumugam R.; Tong, Xiaoying; Curtis, Kevin M.; Norenberg, Michael D.

    2016-01-01

    Intracranial hypertension due to brain edema and associated astrocyte swelling is a potentially lethal complication of acute liver failure (ALF). Mechanisms of edema formation are not well understood but elevated levels of blood and brain ammonia and its byproduct glutamine have been implicated in this process. We examined mRNA and protein expression of the water channel protein aquaporin-4 (AQP4) in cerebral cortex in a rat model of ALF induced by the hepatotoxin thioacetamide. Rats with ALF showed increased AQP4 protein in the plasma membrane (PM). Total tissue levels of AQP4 protein and mRNA levels were not altered indicating that increased AQP4 is not transcriptionally mediated but is likely due to a conformational change in the protein, i.e. a more stable anchoring of AQP4 to the PM and/or interference with its degradation. By immunohistochemistry there was an increase in AQP4 immunoreactivity in the PM of perivascular astrocytes in ALF. Rats with ALF showed increased levels of α-syntrophin, a protein involved in the anchoring of AQP4 to perivascular astrocytic end-feet. Increased AQP4 and α-syntrophin levels were inhibited by L-histidine, an inhibitor of glutamine transport into mitochondria, suggesting a role for glutamine in the increase of PM levels of AQP4. These results indicate that increased AQP4 PM levels in perivascular astrocytic end-feet are likely critical to the development of brain edema in ALF. PMID:20720509

  15. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

    DEFF Research Database (Denmark)

    Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E

    2010-01-01

    Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and....../or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally......(6266) (p edema in mice with ALF....

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

    Science.gov (United States)

    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

  17. Insulin resistance in uremia: Insulin receptor kinase activity in liver and muscle from chronic uremic rats

    International Nuclear Information System (INIS)

    Cecchin, F.; Ittoop, O.; Sinha, M.K.; Caro, J.F.

    1988-01-01

    The authors have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. 125 I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the β-subunit and insulin receptor kinase activity using Glu 80 , Tyr 20 as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristics of the receptors, as determined by electrophoretic mobilities of affinity labeled α-subunit and the phosphorylated β-subunit, were normal in uremia. 125 I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus the data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase

  18. Pregnancy-induced insulin resistance in liver and skeletal muscles of the conscious rabbit

    International Nuclear Information System (INIS)

    Hauguel, S.; Gilbert, M.; Girard, J.

    1987-01-01

    Insulin sensitivity of maternal nonuterine tissues (liver and skeletal muscles) has been investigated in the conscious rabbit during late gestation (24 and 30 days). The specific effect of insulin on glucose production and utilization was evaluated with the hyperinsulinemic euglycemic clamp technique using two types of labelled microspheres ( 57 Co and 113 Sn). The net balance of glucose across the hindlimb muscles was studied by means of the Fick principle in basal and insulin stimulated conditions (clamp study). The results show that an insulin-resistant state developed between days 24 and 30 of gestation in the rabbit and involves both glucose producing (liver) and utilizing (muscles) tissues. On day 30 of gestation, muscle glucose uptake was not significantly stimulated at a plasma insulin concentration of 700 μU/ml determined by radioimmunoassay, whereas it was stimulated by 30-40% in nonpregnant and 24 day pregnant rabbits. At similar plasma insulin concentration, endogenous glucose production was suppressed by 85% in both nonpregnant and 24 day pregnant rabbits, whereas it was decreased by only 30% in 30 day pregnant rabbits. The present data suggest that hindlimb muscles of late pregnant rabbits are able to reduce their insulin-induced glucose utilization. This could contribute to meet the glucose requirements of pregnant uterus in late gestation

  19. Lead concentrations in fresh water, muscle, gill and liver of catla catla (hamilton) from keenjhar lake

    International Nuclear Information System (INIS)

    Korai, A.L.; Sahato, G.A.

    2008-01-01

    This study of the abundance and distribution of lead in water and freshwater fish Catla catla (Ham.) from Keenjhar Lake was conducted during January 2003 to December 2005. The lead content was determined in water and in muscle, gill and liver tissue of Catla catla (Ham.) by using a graphite furnace atomic absorption spectrometry. The lead concentrations in water samples were in the range of 0.076 and 0.225 macro g L-1 during the years of 2003, 2004 and 2005. The lead concentrations in the tissues of Catla catla (Ham.) varied, with liver > gill > muscle. The concentrations in muscle, gill and liver were in the range of 0.7-2.39 micro g g/sub -1/, 0.74-2.25 micro g g/sub -1/ and 0.89-2.68 micro g g/sub -1/ (dry weight) during 2003, 2004 and 2005. 9.87 % did not exceed the UK limit of 1.0 micro g g/sub -1/ (1979), 45.67 % were lower than the (USFDA) level of 1.3 micro g g/sub -1/ (USEPA 1997) and remaining 44.46 % were well below than 4.88 micro g g/sub -1/ (USEPA 1990). The levels in the water samples were also below the permissible level of less then 50 micro g L/sub -1/ recommended by (WHO 1984). (author)

  20. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    International Nuclear Information System (INIS)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-01-01

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage

  1. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Richardson, Jason R. [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States); Heck, Diane E. [Environmental Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  2. Methods of measuring metabolism during surgery in humans: focus on the liver-brain relationship.

    Science.gov (United States)

    Battezzati, Alberto; Bertoli, Simona

    2004-09-01

    The purpose of this work is to review recent advances in setting methods and models for measuring metabolism during surgery in humans. Surgery, especially solid organ transplantation, may offer unique experimental models in which it is ethically acceptable to gain information on difficult problems of amino acid and protein metabolism. Two areas are reviewed: the metabolic study of the anhepatic phase during liver transplantation and brain microdialysis during cerebral surgery. The first model offers an innovative approach to understand the relative role of liver and extrahepatic organs in gluconeogenesis, and to evaluate whether other organs can perform functions believed to be exclusively or almost exclusively performed by the liver. The second model offers an insight to intracerebral metabolism that is closely bound to that of the liver. The recent advances in metabolic research during surgery provide knowledge immediately useful for perioperative patient management and for a better control of surgical stress. The studies during the anhepatic phase of liver transplantation have showed that gluconeogenesis and glutamine metabolism are very active processes outside the liver. One of the critical organs for extrahepatic glutamine metabolism is the brain. Microdialysis studies helped to prove that in humans there is an intense trafficking of glutamine, glutamate and alanine among neurons and astrocytes. This delicate network is influenced by systemic amino acid metabolism. The metabolic dialogue between the liver and the brain is beginning to be understood in this light in order to explain the metabolic events of brain damage during liver failure.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Steven D Kunkel

    Full Text Available 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.

  5. Exercise-induced liver chemokine CXCL-1 expression is linked to muscle-derived interleukin-6 expression

    DEFF Research Database (Denmark)

    Pedersen, Line; Pilegaard, Henriette; Hansen, Jakob

    2011-01-01

    interleukin-6 (IL-6) and muscle IL-6 mRNA. In contrast, exercise-induced regulation of liver CXCL-1 mRNA expression was completely blunted in IL-6 knockout mice. Based on these findings, we examined the possible existence of a muscle-to-liver axis by overexpressing IL-6 in muscles. This resulted in increases...... in serum CXCL-1 (5-fold) and liver CXCL-1 mRNA expression (24-fold) compared with control. Because IL-6 expression and release are known to be augmented during exercise in glycogen-depleted animals, CXCL-1 and IL-6 expression were examined after exercise in overnight-fasted mice.We found that fasting...... significantly augmented serum CXCL-1, and CXCL-1 expression in liver and muscle. Taken together, these data indicate that liver is the main source of serum CXCL-1 during exercise in mice, and that the CXCL-1 expression in the liver is regulated by muscle-derived IL-6....

  6. Comparison of plasma, liver, and skeletal muscle carnitine concentrations in cats with idiopathic hepatic lipidosis and in healthy cats.

    Science.gov (United States)

    Jacobs, G; Cornelius, L; Keene, B; Rakich, P; Shug, A

    1990-09-01

    Concentrations of total, free, and esterified carnitine were determined in plasma, liver, and skeletal muscle from cats with idiopathic hepatic lipidosis and compared with values from healthy cats. The mean concentrations of plasma, liver, and skeletal muscle total carnitine; plasma and skeletal muscle free carnitine; and plasma and liver esterified carnitine were greater (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. The mean for the ratio of free/total carnitine in plasma and liver was lower (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. These data suggest that carnitine deficiency does not contribute to the pathogenesis of feline idiopathic hepatic lipidosis.

  7. Quantitative multivoxel H-1 MR spectroscopy of the brain in children with acute liver failure

    NARCIS (Netherlands)

    Sijens, Paul E.; Alkefaji, Heyder; Lunsing, Roelineke J.; van Spronsen, Francjan J.; Meiners, Linda C.; Oudkerk, Matthijs; Verkade, Henkjan J.

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx)

  8. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema...

  9. Muscle fatigue in fibromyalgia is in the brain, not in the muscles

    DEFF Research Database (Denmark)

    Bandak, Elisabeth; Amris, Kirstine; Bliddal, Henning

    2013-01-01

    To investigate relationships between perceived and objectively measured muscle fatigue during exhausting muscle contractions in women with fibromyalgia (FM) compared with healthy controls (HC).......To investigate relationships between perceived and objectively measured muscle fatigue during exhausting muscle contractions in women with fibromyalgia (FM) compared with healthy controls (HC)....

  10. Determination of boron distribution in rat's brain, kidney and liver

    Energy Technology Data Exchange (ETDEWEB)

    Pazirandeh, Ali [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Science and Technology Research Center, AEOI, Tehran (Iran, Islamic Republic of)], E-mail: paziran@khayam.ut.ac.ir; Jameie, Behnam [Neuroscience Lab, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Zargar, Maysam [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2009-07-15

    To determine relative boron distribution in rat's brain, liver and kidney, a mixture of boric acid and borax, was used. After transcardial injection of the solution, the animals were sacrificed and the brain, kidney and liver were removed. The coronal sections of certain areas of the brain were prepared by freezing microtome. The slices were sandwiched within two pieces of CR-39. The samples were bombarded in a thermal neutron field of the TRR pneumatic facility. The alpha tracks are registered on CR-39 after being etched in NaOH. The boron distribution was determined by counting these alpha tracks CR-39 plastics. The distribution showed non-uniformity in brain, liver and kidney.

  11. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    Science.gov (United States)

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  12. Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans

    DEFF Research Database (Denmark)

    Xu, G.; Hansen, J S; Zhao, Jian-xin

    2016-01-01

    BACKGROUND: Plasma acylcarnitine levels are elevated by physiological conditions such as fasting and exercise but also in states of insulin resistance and obesity. AIM: To elucidate the contribution of liver and skeletal muscle to plasma acylcarnitines in the fasting state and during exercise...... in humans. METHODS: In 2 independent studies, young healthy males were fasted overnight and performed an acute bout of exercise to investigate either acylcarnitines in skeletal muscle biopsies and arterial-to-venous plasma differences over the exercising and resting leg (n = 9) or the flux over the hepato......-splanchnic bed (n = 10). RESULTS: In the fasting state, a pronounced release of C2- and C3-carnitines from the hepato-splanchnic bed and an uptake of free carnitine by the legs were detected. Exercise further increased the release of C3-carnitine from the hepato-splanchnic bed and the uptake of free carnitine...

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

    International Nuclear Information System (INIS)

    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- 3 H] and [U- 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

  14. Liver overload in Brazilian triathletes after half-ironman competition is related muscle fatigue.

    Science.gov (United States)

    Bürger-Mendonça, Marcos; Bielavsky, Monica; Barbosa, Fernanda C R

    2008-01-01

    Triathlon competition is dependent on the athletes' ability to perform each discipline at optimal time, without excessive fatigue influencing the next one. Determine the effects of a long distance triathlon on biochemistry parameters related to liver function. Blood samples from six athletes were collected before (T = 0) and immediately after the triathlon competition (T = 1). AST, ALT and alkaline phosphatase (ALP) values were assessed. Significant changes after triathlon competition were found for AST and ALP and no significant changes were found for ALT over time. A series of metabolically alterations, mainly related to energy production and also to muscle and skeletal adaptations occurs during and after strenuous exercise. The altered status of those metabolical changes cannot directly reflect the intensity of any possible muscular or hepatic damage or overload and elevated AST/ALT ratio is better associated to skeletal muscle lesion during competition.

  15. Estimation of selected residual antibiotics in muscle, kidney, liver, and egg of layer chicken

    International Nuclear Information System (INIS)

    Amjad, H.; Iqbal, J.; Naeem, M.

    2006-01-01

    The present studies were conducted for the estimation of quinolone residues in our local poultry products. The poultry products included muscle, kidney, liver and egg (yolk and white). The quinolones included in this study were, oxolonic acid, flumequine, enrofloxacin, and ciprofloxacin. An assessment of the variation of each analyte (quinolones antibiotic residues) in these products was made. A comparison was made among the analyte (quinolones) concentrations in different tissues/organs and their internationally permissible safer maximum residue limits (MRLS'). Infra Red spectra were used to detect the presence and identification of different quinolones. HPLC with ODS Column and U.V. detector was used for the quantification. (author)

  16. Muscle metabolism and whole blood amino acid profile in patients with liver disease.

    Science.gov (United States)

    Dam, Gitte; Sørensen, Michael; Buhl, Mads; Sandahl, Thomas D; Møller, Niels; Ott, Peter; Vilstrup, Hendrik

    2015-01-01

    Branched-chain amino acids (BCAA) are used in liver cirrhosis to promote protein synthesis, support ammonia detoxification, and treat hepatic encephalopathy. Cirrhosis leads to subnormal BCAA plasma concentrations and studies indicate that levels are decreased due to their role in muscle ammonia removal. Muscle contribution has not been fully elucidated. We studied muscle amino acid metabolism in six healthy subjects, 13 cirrhosis patients and six patients with an episode of alcoholic hepatitis. Subjects had catheters inserted into the femoral artery and vein to obtain arterial (A) and venous (V) concentrations of amino acids (μmol/L blood). BCAA concentrations were lower in patients with cirrhosis compared to healthy subjects (p BCAA uptake was variable and on average higher in patients with alcoholic hepatitis and patients with stable cirrhosis compared to healthy subjects (mean A-V difference 0.5 and 32 vs. - 12 μmol/L blood) (p = 0.22). The release of aromatic amino acids (AAA) was comparable in the three groups (P > 0.30). The BCAA/AAA (Fischer's ratio) was lower in patients with cirrhosis and patients with alcoholic hepatitis compared to healthy subjects (mean 1.65, 1.17 and 2.73, both p BCAA and higher AAA blood concentrations compared to healthy subjects. The trend towards an increased muscle uptake of BCAA may have contributed but this was not significant.

  17. Inhibition of the thioredoxin system in the brain and liver of zebra-seabreams exposed to waterborne methylmercury

    International Nuclear Information System (INIS)

    Branco, Vasco; Canario, Joao; Holmgren, Arne; Carvalho, Cristina

    2011-01-01

    Mercury compounds were recently found to interact in vitro with the thioredoxin system, inhibiting both Thioredoxin (Trx) and Thioredoxin reductase (TrxR). In order to evaluate if Trx and TrxR are affected in vivo by methylmercury (MeHg), we exposed juvenile zebra-seabreams to different concentrations of this toxicant in water for 28 days followed by a 14-day depuration period. Methylmercury accumulated to a larger extent in the kidney and liver of fishes, but decreased significantly during the depuration. During the exposure, MeHg percentage in the liver reached levels above 90% of total mercury (HgT) decreasing to 60% of HgT by the end of the depuration period. In the kidney, MeHg accounted for 50-70% of HgT. In the brain and muscle, mercury accumulated throughout the exposure with all mercury being MeHg. The total mercury kept increasing in these organs during the depuration period. However, in the brain, this increase in HgT was accompanied by a decrease in the MeHg percentage (∼ 10%). In the liver, both Trx and TrxR activities were significantly reduced (TrxR - 40%; Trx - 70%) by the end of the exposure, but recovered to control levels (100%) during the depuration. In the brain, both enzymes where inhibited during the depuration period (TrxR - 75%; Trx - 70%) when some production of inorganic mercury was detected. Activity of glutathione reductase showed increased levels when TrxR activity was low, suggesting complementarity between both systems. These results indicate that in vivo the thioredoxin system is a toxicological target for MeHg with TrxR being particularly affected.

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

    Science.gov (United States)

    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.

  19. Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles.

    Science.gov (United States)

    Nesteruk, Monika; Hennig, Ewa E; Mikula, Michal; Karczmarski, Jakub; Dzwonek, Artur; Goryca, Krzysztof; Rubel, Tymon; Paziewska, Agnieszka; Woszczynski, Marek; Ledwon, Joanna; Dabrowska, Michalina; Dadlez, Michal; Ostrowski, Jerzy

    2014-03-01

    Although mitochondrial dysfunction is implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are not well established. We performed mitochondrial quantitative proteomic and whole transcriptome analysis followed by functional annotations within liver and skeletal muscles, using fasted and non-fasted 16- and 48-week-old high-fat diet (HFD)-fed and normal diet-fed (control group) wild-type C56BL/6J mice, and hyperphagic ob/ob and db/db obese mice. Our study identified 1,675 and 704 mitochondria-associated proteins with at least two peptides in liver and muscle, respectively. Of these, 221 liver and 44 muscle proteins were differentially expressed (adjusted p values ≤ 0.05) between control and all obese mice, while overnight fasting altered expression of 107 liver and 35 muscle proteins. In the liver, we distinguished a network of 27 proteins exhibiting opposite direction of expression changes in HFD-fed and hyperphagic mice when compared to control. The network centered on cytochromes P450 3a11 (Cyp3a11) and 4a14 (Cyp4a14), and fructose-bisphosphate aldolase B (Aldob) proteins which bridged proteins cluster involved in Metabolism of xenobiotics with proteins engaged in Fatty acid metabolism and PPAR signaling pathways. Functional annotations revealed that most of the hepatic molecular alterations, which characterized both obesity and fasting, related to different aspects of energy metabolism (such as Fatty acid metabolism, Peroxisome, and PPAR signaling); however, only a limited number of functional annotations could be selected from skeletal muscle data sets. Thus, our comprehensive molecular overview revealed that both obesity and fasting states induce more pronounced mitochondrial proteome changes in the liver than in the muscles.

  20. Brain and muscle oxygenation monitoring using near-infrared spectroscopy (NIRS) during all-night sleep

    Science.gov (United States)

    Zhang, Zhongxing; Khatami, Ramin

    2013-03-01

    The hemodynamic changes during natural human sleep are still not well understood. NIRS is ideally suited for monitoring the hemodynamic changes during sleep due to the properties of local measurement, totally safe application and good tolerance to motion. Several studies have been conducted using NIRS in both normal subjects and patients with various sleep disorders during sleep to characterize the hemodynamic changing patterns during different sleep stages and during different symptoms such as obstructive apneas. Here we assessed brain and muscle oxygenation changes in 7 healthy adults during all-night sleep with combined polysomnography measurement to test the notion if hemodynamic changes in sleep are indeed brain specific. We found that muscle and brain showed similar hemodynamic changes during sleep initiation. A decrease in HbO2 and tissue oxygenation index (TOI) while an increase in HHb was observed immediately after sleep onset, and an opposite trend was found after transition with progression to deeper slow-wave sleep (SWS) stage. Spontaneous low frequency oscillations (LFO) and very low frequency oscillations (VLFO) were smaller (Levene's test, psleep (LS) and rapid-eye-movement (REM) sleep in both brain and muscle. Spectral analysis of the NIRS signals measured from brain and muscle also showed reductions in VLFO and LFO powers during SWS with respect to LS and REM sleep. These results indicate a systemic attenuation rather than local cerebral reduction of spontaneous hemodynamic activity in SWS. A systemic physiological mechanism may exist to regulate the hemodynamic changes in brain and muscle during sleep.

  1. Multidisciplinary care of obese children and adolescents for one year reduces ectopic fat content in liver and skeletal muscle

    DEFF Research Database (Denmark)

    Fonvig, Cilius Esmann; Chabanova, Elizaveta; Ohrt, Johanne Dam

    2015-01-01

    .49-3.85) and the median age was 14 years (10-17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence...... of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage. CONCLUSIONS: A 1-year multidisciplinary intervention program in the setting...

  2. Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

    Directory of Open Access Journals (Sweden)

    Haider Raza

    2015-02-01

    Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

  3. Analysis of the apoptosis of brain and liver cells induced by ionizing radiation

    International Nuclear Information System (INIS)

    Konoplya, E.F.; Litvinchuk, A.V.; Zajtseva, O.A.; Stashkevich, D.G.

    2010-01-01

    The PCR-analysis of the expression of two oncogenes (bax/bcl-2) in the liver and brain tissues of the animals after being exposed to gamma-rays at doses of 1,0 and 4,0 Gy at remote terms after the action of (30, 60, 90 days) was made. The proofs of start-up of the genetic program of apoptosis of brain and liver cells were obtained. This can be a reason for functional dysfunction of a particular organ and the whole organism. (authors)

  4. Quantitative multivoxel {sup 1}H MR spectroscopy of the brain in children with acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs [University Medical Center Groningen and University of Groningen, Department of Radiology, Beatrix Children' s Hospital, Groningen (Netherlands); Lunsing, Roelineke J. [University Medical Center Groningen and University of Groningen, Department of Child Neurology, Beatrix Children' s Hospital, Groningen (Netherlands); Spronsen, Francjan J. van; Verkade, Henkjan J. [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Beatrix Children' s Hospital, Groningen (Netherlands)

    2008-11-15

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, {gamma}-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  5. Quantitative multivoxel 1H MR spectroscopy of the brain in children with acute liver failure

    International Nuclear Information System (INIS)

    Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs; Lunsing, Roelineke J.; Spronsen, Francjan J. van; Verkade, Henkjan J.

    2008-01-01

    Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase). (orig.)

  6. Multidisciplinary care of obese children and adolescents for one year reduces ectopic fat content in liver and skeletal muscle.

    Science.gov (United States)

    Fonvig, Cilius Esmann; Chabanova, Elizaveta; Ohrt, Johanne Dam; Nielsen, Louise Aas; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

    2015-12-30

    Ectopic fat deposition in liver and skeletal muscle tissue is related to cardiovascular disease risk and is a common metabolic complication in obese children. We evaluated the hypotheses of ectopic fat in these organs could be diminished following 1 year of multidisciplinary care specialized in childhood obesity, and whether this reduction would associate with changes in other markers of metabolic function. This observational longitudinal study evaluated 40 overweight children and adolescents enrolled in a multidisciplinary treatment protocol at the Children's Obesity Clinic, Holbæk, Denmark. The participants were assessed by anthropometry, fasting blood samples (HbA1c, glucose, insulin, lipids, and biochemical variables of liver function), and liver and muscle fat content assessed by magnetic resonance spectroscopy at enrollment and following an average of 12.2 months of care. Univariate linear regression models adjusted for age, sex, treatment duration, baseline degree of obesity, and pubertal developmental stage were used for investigating possible associations. The standard deviation score (SDS) of baseline median body mass index (BMI) was 2.80 (range: 1.49-3.85) and the median age was 14 years (10-17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage. A 1-year multidisciplinary intervention program in the setting of a childhood obesity outpatient clinic confers a biologically important reduction in liver and muscle fat; metabolic improvements that are independent of the magnitude of concurrent weight loss

  7. Antioxidant Role of Pomegranates on Liver and Brain Tissues of Rats Exposed to an Organophosphorus Insecticide

    International Nuclear Information System (INIS)

    Abd Elmonem, H.A.

    2014-01-01

    Toxicities of organophosphorus insecticides cause oxidative damage on many organs such as the liver and brain due to generation of reactive oxygen species. Pomegranate is among the richest fruit in poly - phenols. The aim of this study was to compare between the antioxidant strength of pomegranate juice (PJ) and pomegranate molasses (PM) and their effects on alanine transferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and total protein (TP) in liver and levels of malondialdehyde (MAD), reduced glutathione (GSH) and nitric oxide (NO) in rat liver and brain tissues exposed to 1/10 LD 50 diazinon (DI). Six groups each of 6 male albino rats were used comprising control, DI, PJ, PM, PJ + DI and PM + DI for 15 days. The activities of ALT, AST, and TP concentration in liver have been increased due to treatment of rats with DI. These increases restored to normalcy when rats were supplemented with PJ or PM with DI. The results demonstrate that treatment with DI induced significant increase in MDA and NO concentrations and significant decrease in GSH levels of liver and brain tissues. The administration of PJ or PM along with DI significant decrease in MDA and NO levels and significant increase in GSH level compared to DI-group. The present study suggest that PJ or PM has a potential protective effect as it can elevate antioxidant defense system, lessens induced oxidative dam - ages and protect the brain and liver tissue against DI-induced toxicity. In addition, comaring PJ with PM it was noticed that PJ had higher antioxidant activity as evidenced by increased GSH content and decreased NO level in the liver by greater extend than PM.

  8. Concurrent low brain and high liver uptake on FDG PET are associated with cardiovascular risk factors

    International Nuclear Information System (INIS)

    Nam, Hyun Yeol; Jun, Sung Min; Pak, Kyoung June; Kim, In Joo

    2017-01-01

    Concurrent low brain and high liver uptake are sometimes observed on fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We investigated the potential clinical significance of this uptake pattern related to metabolic syndrome (MS). We retrospectively reviewed data from 264 consecutive males who had undergone general health check-ups, including FDG PET/CT scans. After an overnight fast, the men had their peripheral blood drawn and the levels of various laboratory parameters measured; an FDG PET/CT scan was performed on the same day. We measured the maximum standardized uptake values of the brain and liver from regions of interest manually placed over the frontal cortex at the level of the centrum semiovale and the right lobe of the liver parenchyma, respectively. Fasting blood glucose (FBG; odds ratio [OR] = 1.063, p < 0.001) and glycated hemoglobin (HbA1c; OR = 3.634, p = 0.010) were the strongest predictive factors for low brain FDG uptake, whereas waist circumference (OR = 1.200, p < 0.001) and γ-glutamyl transpeptidase (OR = 1.012, p = 0.001) were the strongest predictive factors for high liver uptake. Eleven subjects (4.2%) showed concurrent low brain and high liver FDG uptake, and all but one of these subjects (90.9%) had MS. Systolic blood pressure, waist circumference, FBG, triglyceride, alanine aminotransferase, insulin resistance (measured by homeostasis model assessment), insulin, HbA1c, and body mass index were higher in subjects with this FDG uptake pattern than in those without (all, p < 0.001). Concurrent low brain and high liver FDG uptake were closely associated with MS. Moreover, subjects with this pattern had higher values for various cardiovascular risk factors than did those without

  9. Concurrent low brain and high liver uptake on FDG PET are associated with cardiovascular risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Hyun Yeol [Dept. of Nuclear Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon (Korea, Republic of); Jun, Sung Min [Dept. of Nuclear Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan (Korea, Republic of); Pak, Kyoung June; Kim, In Joo [Dept. of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of)

    2017-04-15

    Concurrent low brain and high liver uptake are sometimes observed on fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We investigated the potential clinical significance of this uptake pattern related to metabolic syndrome (MS). We retrospectively reviewed data from 264 consecutive males who had undergone general health check-ups, including FDG PET/CT scans. After an overnight fast, the men had their peripheral blood drawn and the levels of various laboratory parameters measured; an FDG PET/CT scan was performed on the same day. We measured the maximum standardized uptake values of the brain and liver from regions of interest manually placed over the frontal cortex at the level of the centrum semiovale and the right lobe of the liver parenchyma, respectively. Fasting blood glucose (FBG; odds ratio [OR] = 1.063, p < 0.001) and glycated hemoglobin (HbA1c; OR = 3.634, p = 0.010) were the strongest predictive factors for low brain FDG uptake, whereas waist circumference (OR = 1.200, p < 0.001) and γ-glutamyl transpeptidase (OR = 1.012, p = 0.001) were the strongest predictive factors for high liver uptake. Eleven subjects (4.2%) showed concurrent low brain and high liver FDG uptake, and all but one of these subjects (90.9%) had MS. Systolic blood pressure, waist circumference, FBG, triglyceride, alanine aminotransferase, insulin resistance (measured by homeostasis model assessment), insulin, HbA1c, and body mass index were higher in subjects with this FDG uptake pattern than in those without (all, p < 0.001). Concurrent low brain and high liver FDG uptake were closely associated with MS. Moreover, subjects with this pattern had higher values for various cardiovascular risk factors than did those without.

  10. Muscle atrophy as pre-sarcopenia in Japanese patients with chronic liver disease: computed tomography is useful for evaluation

    OpenAIRE

    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

    2015-01-01

    Background/Aim 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. Methods We enrolled 988 CLD (736 with na?ve hepatocellular carcinoma) and 372 normal control subjects (NCs). The psoas muscle area index [PI, psoas muscle area at the mid-L3 level in CT (cm2)/...

  11. Muscles, exercise and obesity

    DEFF Research Database (Denmark)

    Pedersen, Bente K; Febbraio, Mark A

    2012-01-01

    During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines....... The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within...... the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal...

  12. Multidimensional control using a mobile-phone based brain-muscle-computer interface.

    Science.gov (United States)

    Vernon, Scott; Joshi, Sanjay S

    2011-01-01

    Many well-known brain-computer interfaces measure signals at the brain, and then rely on the brain's ability to learn via operant conditioning in order to control objects in the environment. In our lab, we have been developing brain-muscle-computer interfaces, which measure signals at a single muscle and then rely on the brain's ability to learn neuromuscular skills via operant conditioning. Here, we report a new mobile-phone based brain-muscle-computer interface prototype for severely paralyzed persons, based on previous results from our group showing that humans may actively create specified power levels in two separate frequency bands of a single sEMG signal. Electromyographic activity on the surface of a single face muscle (Auricularis superior) is recorded with a standard electrode. This analog electrical signal is imported into an Android-based mobile phone. User-modulated power in two separate frequency band serves as two separate and simultaneous control channels for machine control. After signal processing, the Android phone sends commands to external devices via Bluetooth. Users are trained to use the device via biofeedback, with simple cursor-to-target activities on the phone screen.

  13. Studies on estradiol-2/4-hydroxylase activity in rat brain and liver

    International Nuclear Information System (INIS)

    Theron, C.N.

    1985-03-01

    A sensitive and specific radio-enzymatic assay was used to study estradiol-2/4-hydroxylase activity in rat liver microsomes and in microsomes obtained from 6 discrete brain areas of the rat. Kinetic parameters were determined for these enzyme activities. The effects of different P-450 inhibitors on estradiol-2/4-hydroxylase activity in brain and liver microsomes were also studied. In both organs these enzyme activities were found to be located mainly in the microsomal fraction and were inhibited by the 3 P-450 inhibitors tested. The hepatic estradiol-2/4-hydroxylase activity in adult male rats was significantly higher than that of females, but the enzyme activity in the brain did not exhibit a similar sex difference. Furthermore, estradiol-2/4-hydroxylase activity in rat liver was strongly induced by phenobarbitone treatment, but not in the brain. The phenobarbitone-induced activity in male and female rats exhibited significant kinetic differences. In female rats sexual maturation was associated with significant changes in the apparent Km of estradiol-2/4-hydroxylases in the liver and hypothalamus. Evidence was found that the in vitro estradiol-2/4-hydroxylase activity in rat brain and liver is due to more than one form of microsomal P-450. Kinetic studies showed important differences between the estradiol-2/4-hydroxylase activities in the hippocampus and hypothalamus. Significant differences in estradiol-2/4-hydroxylase activities were observed in the 6 brain areas studied, with the hippocampus showing the highest, and the hypothalamus the lowest activity at all developmental stages in both male and female rats

  14. [Study on corresponding areas the liver and lung channels in brain with fMRI].

    Science.gov (United States)

    Xu, Fang-Ming; Xie, Peng; Lü, Fa-Jin; Mou, Jun; Li, Yong-Mei; Zhao, Jian-Nong; Chen, Wei-Juan; Gong, Qi-Yong; Zhao, Li-Bo; Liu, Qing-Jun; Shen, Lin; Zhai, Hong; Yang, De-Yu

    2007-10-01

    To explore distribution of the Liver and Lung Channels in the brain so as to provide imaging basis for construction of channel theory in the brain. Sixty healthy student volunteers were randomly divided into a Liver Channel group (I) and a Lung Channel group (II), and the each group was further divided into five subgroups with 6 volunteers in each subgroup, based on five-shu-point principles which, were Dadun (LR 1, I 1), Xingjian (LR 2, I 2), Taichong (LR 3, I 3), Zhongfeng (LR 4, I 4), Ququan (LR 8, I 5), Shaoshang (LU 11, II 1), Yuji (LU 10, II 2), Taiyuan (LU 9, II 3), Jingqu (LU 8, II 4), and Chize (LU 5, II 5), respectively. In order to observe the brain activating patterns during acupuncture at the different acupoints, functional magnetic resonance imaging (fMRI) technique was adopted. All image data were then analyzed with SPM 2 software. The statistical parameter gram was composed of the pixel P areas, and the commonly activated area of five-shu-point of each channel was considered as the brain distribution of the Liver and Lung Channels. The common areas activated by the five-shu-points of the Liver Channel were homolateral Brodmann area (BA) 34, BA 47, red nucleus, contralateral BA 19, BA 30, BA 39, the superior parietal lobule, cerebellum decline, and bilateral BA 3 and culmen. The common areas activated by the five-shu-points of the Lung Channels included homolateral BA 2, BA 18, BA 35, and contralateral BA 9 and substania nigra. There are relatively specific corresponding brain areas for the Liver and Lung Channels, indicating that there is possible relatively specific connection between channels and the brain.

  15. Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

    NARCIS (Netherlands)

    Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

    We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos.

  16. Brain and liver fatty acid composition changes upon consumption of Lactobacillus rhamnosus LA68.

    Science.gov (United States)

    Ivanovic, Nevena; Minic, Rajna; Djuricic, Ivana; Dimitrijevic, Ljiljana; Sobajic, Sladjana; Zivkovic, Irena; Djordjevic, Brizita

    2015-02-01

    Recent reports suggest that the metabolic activity of the enteric microbiota may influence the fatty acid composition of the host tissue. There are many studies dealing with the influence of lactobacilli on various pathological conditions, and some of the effects are strain-specific. This study was designed to test the effects of a particular Lactobacillus strain, Lactobacillus rhamnosus LA68 on fatty acid composition of the liver and the brain of C57BL/6 mice in the absence of an underlying pathological condition. Female mice were supplemented with live L. rhamnosus LA68 bacteria for the duration of 1 month. Serum biochemistry was analyzed and liver and brain fatty acid composition was assessed by gas-liquid chromatography. Significant changes in liver and brain fatty acid composition were detected. In the liver tissue we detected an increase in palmitoleic acid (p = 0.038), while in the brain compartment we found an increase in palmitic (p = 0.042), stearic (p = 0.017), arachidonic acid (p = 0.009) and docosahexaenoic acid (p = 0.004) for control versus experimental group. These results show discrete changes caused by LA68 strain consumption. Even short duration of administration of LA68 influences the fatty acid composition of the host which adds to the existing knowledge about Lactobacillus host interaction, and adds to the growing knowledge of metabolic intervention possibilities.

  17. Human brain activity associated with painful mechanical stimulation to muscle and bone

    OpenAIRE

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-01-01

    Purpose The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Methods Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain ac...

  18. Acute effects of organotins on brain, liver and kidney in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, R.S.; Kaur, G.; Srivastava, R.C.; Srivastava, T.N.

    1985-01-01

    Effects of dioctyltin oxide (DOTO) tricyclohexyltin hydroxide (TCHTOH) and tributyltin oxide (TBTO) were examined on some enzymic activities in liver and kidney and biogenic amines level in brain of rats at 24 hours after single subcutaneous administration (25 ..mu..mole/100 g B. Wt.). All the organotin compounds produced a significant increase in the activity of alkaline phosphatase and adenosin triphosphatase and decrease in monoamine oxidase in both liver and kidney. DOTO and TCHTOH were more effective in impairing the activity of succinate dehydrogenase in liver. Concentrations of ..gamma..-aminobutyric acid (GABA) and dopamine were found to be significantly decreased in brain however, acetylcholine concentration remained unaltered. These results suggest that organotin compounds DOTO and TCHTOH are more toxic to rats than TBTO. 30 references, 3 tables.

  19. Determination and depletion of residues of carbadox, tylosin, and virginiamycin in kidney, liver, and muscle of pigs in feeding experiments.

    Science.gov (United States)

    Lauridsen, M G; Lund, C; Jacobsen, M

    1988-01-01

    The results of residue determinations of the growth promotors carbadox, tylosin, and virginiamycin in kidney, liver, and muscle from pigs in feeding experiments are described as well as the analytical methods used. Residues of the carbadox metabolite quinoxaline-2-carboxylic acid were found in liver from pigs fed 20 mg/kg in the diet with a withdrawal time of 30 days. No residues were detected in muscle with zero withdrawal time. The limit of determination was 0.01 mg/kg for both tissues. No residues of virginiamycin and tylosin were found in pigs fed 50 and 40 mg/kg, respectively, in the diet, even with zero withdrawal time. Residues of tylosin of 0.06 mg/kg and below were detected in liver and kidney from pigs fed 200 or 400 mg/kg and slaughtered within 3 h after the last feeding.

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

    Science.gov (United States)

    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 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.

  1. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

    Directory of Open Access Journals (Sweden)

    Halina Baran*

    2016-01-01

    Full Text Available Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3, respiratory control index (RC and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM or succinate (10 mM and in the presence of L-tryptophan metabolites (1 mM or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver

  2. Upper Limb Muscle and Brain Activity in Light Assembly Task on Different Load Levels

    Science.gov (United States)

    Zadry, Hilma Raimona; Dawal, Siti Zawiah Md.; Taha, Zahari

    2010-10-01

    A study was conducted to investigate the effect of load on upper limb muscles and brain activities in light assembly task. The task was conducted at two levels of load (Low and high). Surface electromyography (EMG) was used to measure upper limb muscle activities of twenty subjects. Electroencephalography (EEG) was simultaneously recorded with EMG to record brain activities from Fz, Pz, O1 and O2 channels. The EMG Mean Power Frequency (MPF) of the right brachioradialis and the left upper trapezius activities were higher on the high-load task compared to low-load task. The EMG MPF values also decrease as time increases, that reflects muscle fatigue. Mean power of the EEG alpha bands for the Fz-Pz channels were found to be higher on the high-load task compared to low-load task, while for the O1-O2 channels, they were higher on the low-load task than on the high-load task. These results indicated that the load levels effect the upper limb muscle and brain activities. The high-load task will increase muscle activities on the right brachioradialis and the left upper tapezius muscles, and will increase the awareness and motivation of the subjects. Whilst the low-load task can generate drowsiness earlier. It signified that the longer the time and the more heavy of the task, the subjects will be more fatigue physically and mentally.

  3. 1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents.

    Science.gov (United States)

    Fonvig, Cilius Esmann; Chabanova, Elizaveta; Andersson, Ehm Astrid; Ohrt, Johanne Dam; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

    2015-01-01

    This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children. Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years. In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol. Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.

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

    Science.gov (United States)

    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.

  5. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-β.

    Science.gov (United States)

    Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

    2012-11-14

    Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA.

  6. Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

    Science.gov (United States)

    Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Morsy, Safaa M Youssef; Omara, Enayat A; Sleem, Amany A

    2014-05-01

    Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

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

    Directory of Open Access Journals (Sweden)

    Luis Jesuino de Oliveira Andrade

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

    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

  9. A high-fructose diet induces changes in pp185 phosphorylation in muscle and liver of rats

    Directory of Open Access Journals (Sweden)

    M. Ueno

    2000-12-01

    Full Text Available Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. These early steps in insulin action are essential for the metabolic effects of insulin. Feeding animals a high-fructose diet results in insulin resistance. However, the exact molecular mechanism underlying this effect is unknown. In the present study, we determined the levels and phosphorylation status of the insulin receptor and pp185 (IRS-1/2 in liver and muscle of rats submitted to a high-fructose diet evaluated by immunoblotting with specific antibodies. Feeding fructose (28 days induced a discrete insulin resistance, as demonstrated by the insulin tolerance test. Plasma glucose and serum insulin and cholesterol levels of the two groups of rats, fructose-fed and control, were similar, whereas plasma triacylglycerol concentration was significantly increased in the rats submitted to the fructose diet (P<0.05. There were no changes in insulin receptor concentration in the liver or muscle of either group. However, insulin-stimulated receptor autophosphorylation was reduced to 72 ± 4% (P<0.05 in the liver of high-fructose rats. The IRS-1 protein levels were similar in both liver and muscle of the two groups of rats. In contrast, there was a significant decrease in insulin-induced pp185 (IRS-1/2 phosphorylation, to 83 ± 5% (P<0.05 in liver and to 77 ± 4% (P<0.05 in muscle of the high-fructose rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance induced by high-fructose feeding.

  10. Magnesium enhances exercise performance via increasing glucose availability in the blood, muscle, and brain during exercise.

    Directory of Open Access Journals (Sweden)

    Hsuan-Ying Chen

    Full Text Available Glucose mobilization and utilization in the periphery and central nervous system are important during exercise and are responsible for exercise efficacy. Magnesium (Mg is involved in energy production and plays a role in exercise performance. This study aimed to explore the effects of Mg on the dynamic changes in glucose and lactate levels in the muscle, blood and brain of exercising rats using a combination of auto-blood sampling and microdialysis. Sprague-Dawley rats were pretreated with saline or magnesium sulfate (MgSO4, 90 mg/kg, i.p. 30 min before treadmill exercise (20 m/min for 60 min. Our results indicated that the muscle, blood, and brain glucose levels immediately increased during exercise, and then gradually decreased to near basal levels in the recovery periods of both groups. These glucose levels were significantly enhanced to approximately two-fold (P<0.05 in the Mg group. Lactate levels in the muscle, blood, and brain rapidly and significantly increased in both groups during exercise, and brain lactate levels in the Mg group further elevated (P<0.05 than those in the control group during exercise. Lactate levels significantly decreased after exercise in both groups. In conclusion, Mg enhanced glucose availability in the peripheral and central systems, and increased lactate clearance in the muscle during exercise.

  11. Gene co-expression networks in liver and muscle transcriptome reveal sex-specific gene expression in lambs fed with a mix of essential oils

    DEFF Research Database (Denmark)

    Sabino, Marcella; Carmelo, Victor Adriano Okstoft; Mazzoni, Gianluca

    2018-01-01

    the potential of RNA-Sequencing data in order to evaluate the effect of an EO supplementary diet on gene expression in both lamb liver and muscle. Using a treatment and sex interaction model, 13 and 4 differentially expressed genes were identified in liver and muscle respectively. Sex-specific differentially...... on the expression profile of both liver and muscle tissues. We hypothesize that the presence of EOs could have beneficial effects on wellness of male lamb and further analyses are needed to understand the biological mechanisms behind the different effect of EO metabolites based on sex. Using lamb as a model...

  12. Human brain activity associated with painful mechanical stimulation to muscle and bone.

    Science.gov (United States)

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-08-01

    The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

  13. Muscle-Eye-Brain Disease; a Rare Form of Syndromic Congenital Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Gosal Gurinder S

    2011-03-01

    Full Text Available Congenital muscular dystrophy (CMD is a heterogeneous group of disorders characterized by muscular hypotonia since birth and the histologic features of muscular dystrophy. Syndromic congenital muscular dystrophies are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We present a case of a rare form of syndromic congenital muscular dystrophy in an eight year old girl, born of first- degree consanguinity. She had: global developmental delay; a seizure disorder; hypotonia; progressive muscle contractures including bilateral symmetrical flexion contractures of hips, knees, equinus contracture and thoracolumbar scoliosis; diminished deep tendon reflexes: bilateral premature cataract; pseudophakia; and nystagmus. The patient was also highly myopic. Based on clinical features, muscle biopsy and MRI of the brain, a diagnosis of muscle- eye- brain disease was made. Identification of these patients may help to prevent this crippling disorder in the future siblings of probands by utilizing genetic counselling and mutation analysis.

  14. Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

    International Nuclear Information System (INIS)

    Chen, Qi-Liang; Gong, Yuan; Luo, Zhi; Zheng, Jia-Lang; Zhu, Qing-Ling

    2013-01-01

    Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

  15. Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Gong, Yuan [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Luo, Zhi, E-mail: luozhi99@mail.hzau.edu.cn [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Zheng, Jia-Lang; Zhu, Qing-Ling [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China)

    2013-10-15

    Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

  16. Feeding during the resting phase causes profound changes in physiology and desynchronization between liver and muscle rhythms of rats.

    Science.gov (United States)

    Opperhuizen, Anne-Loes; Wang, Dawei; Foppen, Ewout; Jansen, Remi; Boudzovitch-Surovtseva, Olga; de Vries, Janneke; Fliers, Eric; Kalsbeek, Andries

    2016-11-01

    Shiftworkers run an increased risk of developing metabolic disorders, presumably as a result of disturbed circadian physiology. Eating at a time-of-day that is normally dedicated to resting and fasting, may contribute to this association. The hypothalamus is the key brain area that integrates different inputs, including environmental time information from the central biological clock in the suprachiasmatic nuclei, with peripheral information on energy status to maintain energy homeostasis. The orexin system within the lateral hypothalamus is an important output of the suprachiasmatic nuclei involved in the control of sleep/wake behavior and glucose homeostasis, among other functions. In this study, we tested the hypothesis that feeding during the rest period disturbs the orexin system as a possible underlying contributor to metabolic health problems. Male Wistar rats were exposed to an 8-week protocol in which food was available ad libitum for 24-h, for 12-h during the light phase (i.e., unnatural feeding time) or for 12-h during the dark phase (i.e., restricted feeding, but at the natural time-of-day). Animals forced to eat at an unnatural time, i.e., during the light period, showed no changes in orexin and orexin-receptor gene expression in the hypothalamus, but the rhythmic expression of clock genes in the lateral hypothalamus was absent in these animals. Light fed animals did show adverse changes in whole-body physiology and internal desynchronization of muscle and liver clock and metabolic gene expression. Eating at the 'wrong' time-of-day thus causes internal desynchronization at different levels, which in the long run may disrupt body physiology. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin

    DEFF Research Database (Denmark)

    André, F M; Gehl, J; Sersa, G

    2008-01-01

    Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across the permeab......Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across...... the permeabilized membrane. To investigate this further, combinations of permeabilizing short high-voltage pulses (HV; hundreds of V/cm) and mainly electrophoretic long low-voltage pulses (LV; tens of V/cm) were investigated in muscle, liver, tumor, and skin in rodent models. The following observations were made......, but not to liver; and (4) efficient gene electrotransfer was achieved with HV field strengths below the detectability thresholds for permeabilization; and (5) the lag time interval between the HV and LV pulses decreased sensitivity to the HV pulses, enabling a wider HV amplitude range. In conclusion, HV plus LV...

  18. Metabolic Circuit Involving Free Fatty Acids, microRNA 122, and Triglyceride Synthesis in Liver and Muscle Tissues.

    Science.gov (United States)

    Chai, Chofit; Rivkin, Mila; Berkovits, Liav; Simerzin, Alina; Zorde-Khvalevsky, Elina; Rosenberg, Nofar; Klein, Shiri; Yaish, Dayana; Durst, Ronen; Shpitzen, Shoshana; Udi, Shiran; Tam, Joseph; Heeren, Joerg; Worthmann, Anna; Schramm, Christoph; Kluwe, Johannes; Ravid, Revital; Hornstein, Eran; Giladi, Hilla; Galun, Eithan

    2017-11-01

    Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of Luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines. We measured levels of microRNAs and mRNAs by quantitative real-time PCR analysis of RNA extracted from plasma, liver, muscle, and adipose tissues of C57BL/6 mice given the FFA-inducer CL316243. MIR122 was inhibited using an inhibitor of MIR122. Metabolic profiles of mice were determined using metabolic chambers and by histologic analyses of liver tissues. We performed RNA sequence analyses to identify metabolic pathways involving MIR122. We validated human Agpat1 and Dgat1 mRNAs, involved in triglyceride synthesis, as targets of MIR122. FFAs increased MIR122 expression in livers of mice by activating the retinoic acid-related orphan receptor alpha, and induced secretion of MIR122 from liver to blood. Circulating MIR122 entered muscle and adipose tissues of mice, reducing mRNA levels of genes involved in triglyceride synthesis. Mice injected with an inhibitor of MIR122 and then given CL316243, accumulated triglycerides in liver and muscle tissues, and had reduced rates of β-oxidation. There was a positive correlation between level of FFAs and level of MIR122 in plasma samples from 6 healthy individuals, collected before and during fasting. In biochemical and histologic studies of plasma, liver, muscle, and adipose tissues from mice, we found that FFAs increase hepatic expression and secretion of MIR122, which regulates energy storage vs expenditure in liver and peripheral tissues. Strategies to reduce

  19. Prognostic significance of low skeletal muscle mass compared with protein-energy malnutrition in liver cirrhosis.

    Science.gov (United States)

    Nishikawa, Hiroki; Enomoto, Hirayuki; Ishii, Akio; Iwata, Yoshinori; Miyamoto, Yuho; Ishii, Noriko; Yuri, Yukihisa; Takata, Ryo; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Yoh, Kazunori; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Iijima, Hiroko; Nishiguchi, Shuhei

    2017-09-01

    To investigate the impact of low skeletal muscle mass (LSMM) on survival as compared with protein-energy malnutrition (PEM) in patients with liver cirrhosis (LC). A total of 206 individuals with LC were analyzed. We retrospectively examined the impact of LSMM, as defined by psoas muscle mass at the third lumber on computed tomography, on survival as compared with PEM. In terms of comparison of the effects of LSMM and PEM on survival, we used time-dependent receiver operating characteristics (ROC) analysis. Our study cohort included 115 men and 91 women with a median age of 67 years. There were 140 patients with Child-Pugh A, 62 with Child-Pugh B, and 4 with Child-Pugh C. A total of 117 patients (56.8%) had LSMM and 52 patients (25.2%) had PEM. The proportion of PEM in patients with LSMM (31.62%, 37/117) was significantly higher than in patients without LSMM (16.85%, 15/89) (P = 0.0229). In the multivariate analysis for the entire cohort, the presence of hepatocellular carcinoma, lower body mass index, presence of LSMM, lower triglyceride value, poorer renal function, and higher des-γ-carboxy prothrombin value were found to be significant adverse predictors linked to overall survival, while presence of PEM tended to be significant. In the time-dependent ROC analysis, all area under the ROCs for survival in LSMM at each time point were higher than those in PEM except for Child-Pugh B patients. In this comparison of LSMM and PEM on clinical outcomes in LC patients, it was shown that LSMM may have stronger prognostic impact than PEM. © 2016 The Japan Society of Hepatology.

  20. Expression of the Murine Duchenne Muscular Dystrophy Gene in Muscle and Brain

    Science.gov (United States)

    Chamberlain, Jeffrey S.; Pearlman, Joel A.; Muzny, Donna M.; Gibbs, Richard A.; Ranier, Joel E.; Reeves, Alice A.; Caskey, C. Thomas

    1988-03-01

    Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.

  1. Ratio of muscle mass to fat mass assessed by bioelectrical impedance analysis is significantly correlated with liver fat accumulation in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kurinami, Noboru; Sugiyama, Seigo; Morita, Ayami; Yoshida, Akira; Hieshima, Kunio; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouch, Katsunori; Jinnouchi, Tomio; Jinnouchi, Hideaki

    2018-05-01

    Obesity and ectopic fat accumulation are important conditions of type 2 diabetes mellitus (T2DM). Our aim was to determine whether bioelectrical impedance body composition analysis combined with blood test results could estimate liver ectopic fat accumulation in patients with treatment-naïve T2DM. Subjects were 119 untreated T2DM patients. Computed tomography scans were performed to calculate the liver to spleen attenuation ratio (L/S ratio) as a measure of liver fat accumulation, with excess liver fat accumulation defined as an L/S ratio analysis using InBody770. The Nagelkerke R 2 test showed that the muscle mass/fat mass ratio (muscle/fat ratio) was the most suitable variable among anthropometric factors and body component indexes for estimating liver fat accumulation. The muscle/fat ratio was significantly correlated with the L/S ratio (ρ = 0.4386, P analysis showed that the muscle/fat ratio (odds ratio 0.40, 95% confidence interval 0.22-0.73, P ratio 1.06, 95% confidence interval 1.02-1.10, P analysis, the cutoff value of the muscle/fat ratio for excess liver fat accumulation was 2.34. In patients with treatment-naïve T2DM, the muscle/fat ratio and ALT are useful for estimating the presence of excess liver fat accumulation in daily clinical practice. Copyright © 2018. Published by Elsevier B.V.

  2. Muscle and liver glycogen utilization during prolonged lift and carry exercise: male and female responses.

    Science.gov (United States)

    Price, Thomas B; Sanders, Kimberly

    2017-02-01

    This study examined the use of carbohydrates by men and women during lift/carry exercise. Effects of menstrual cycle variation were examined in women. Twenty-five subjects (15 M, 10 F) were studied; age 25 ± 2y M, 26 ± 3y F, weight 85 ± 3 kg* M, 63 ± 3 kg F, and height 181 ± 2 cm* M, 161 ± 2 cm F (* P  Glycogen utilization was tracked with natural abundance C-13 NMR of quadriceps femoris and biceps brachialis muscles, and in the liver at rest and throughout the exercise period. Males completed more of the 180 min protocol than females [166 ± 9 min M, 112 ± 16 min* F (L), 88 ± 16 min** F (F) (* P  = 0.0036, ** P  glycogen depletion was similar between sexes and within females in L/F phases [4.7 ± 0.8 mmol/L-h M, 4.5 ± 2.4 mmol/L-h F (L), 10.3 ± 3.5 mmol/L-h F (F)]. Biceps glycogen depletion was greater in females [2.7 ± 0.9 mmol/L-h M, 10.3 ± 1.3 mmol/L-h* F (L), 16.8 ± 4.8 mmol/L-h** F (F) (* P  = 0.0004, ** P  = 0.0122)]. Resting glycogen levels were higher in females during the follicular phase ( P  = 0.0077). Liver glycogen depletion increased during exercise, but was not significant. We conclude that with non-normalized lift/carry exercise: (1) Based on their smaller size, women are less capable of completing and work their upper body harder than men. (2) Women and men work their lower body at similar levels. (3) Women store more quadriceps carbohydrate during the follicular phase. (4) The liver is not significantly challenged by this protocol. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  3. Impact of dietary fatty acids on muscle composition, liver lipids, milt composition and sperm performance in European eel

    DEFF Research Database (Denmark)

    Butts, Ian; Baeza, R.; Støttrup, Josianne

    2015-01-01

    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...... 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...

  4. Brain MRI findings in acute hepatic encephalopathy in liver transplant recipients.

    Science.gov (United States)

    Guo, Ruo-Mi; Li, Qing-Ling; Zhong, Li-Ru; Guo, Yu; Jiao, Ju; Chen, Shao-Qiong; Wang, Jin; Zhang, Yong

    2018-06-01

    Acute hepatic encephalopathy has significant morbidity and mortality in liver transplant recipients unless it is promptly treated. We evaluated the brain magnetic resonance (MR) imaging findings associated with acute hepatic encephalopathy in transplant recipients. We retrospectively reviewed the clinical and imaging data and outcomes of twenty-five liver transplant patients (16 male; mean age, 49.3 years) with clinically diagnosed acute hepatic encephalopathy and forty liver transplant patients (20 males; mean age, 45.5 years) without neurological symptoms suggestive of hepatic encephalopathy at our institution. Bilateral symmetric hyperintensities of the insular cortex and cingulate gyrus were observed in twenty-one patients (84.00%), bilateral symmetric extensive increased cortical signal intensity (involving two or more regions) was observed in 72.00% of the patients, leptomeningeal enhancement in 73.68%, and visualization of prominent venules in 52.00%. The most common symptom at diagnosis was rigidity (n = 14), and the plasma ammonia levels ranged from 68.63 to 192.16 μmol/L. After active treatment, 17 patients gradually recovered, four patients suffered from mild or moderate neurologic deficits, and four patients with widespread brain edema died. The specific brain MR imaging features were bilateral symmetric increased cortical signal intensity, especially in the insular cortex and cingulate gyrus, leptomeningeal enhancement, visualization of the prominent venules, and widespread brain edema. These features may indicate poor prognosis and should alert radiologists to the possibility of acute hepatic encephalopathy in liver transplant recipients and encourage clinicians to prepare appropriate treatment in advance.

  5. Impaired brain glymphatic flow in a rodent model of chronic liver disease and minimal hepatic encephalopathy

    OpenAIRE

    Lythgoe, Mark; Hosford, Patrick; Arias, Natalia; Gallego-Duran, Rocio; Hadjihambi, Anna; Jalan, Rajiv; Gourine, Alexander; Habtesion, Abeba; Davies, Nathan; Harrison, Ian

    2017-01-01

    Neuronal function is exquisitely sensitive to alterations in extracellular environment. In patients with hepatic encephalopathy (HE), accumulation of metabolic waste products and noxious substances in the interstitial fluid of the brain may contribute to neuronal dysfunction and cognitive impairment. In a rat model of chronic liver disease, we used an emerging dynamic contrast-enhanced MRI technique to assess the efficacy of the glymphatic system, which facilitates clearance of solutes from t...

  6. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism.

    Science.gov (United States)

    Li, Shuang; Wang, S U; Guo, Zhi-Gang; Huang, Ning; Zhao, Fan-Rong; Zhu, Mo-Li; Ma, Li-Juan; Liang, Jin-Ying; Zhang, Yu-Lin; Huang, Zhong-Lin; Wan, Guang-Rui

    2015-11-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism.

  7. 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).

    Science.gov (United States)

    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.

  8. Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity.

    Science.gov (United States)

    Sartorius, Tina; Peter, Andreas; Schulz, Nadja; Drescher, Andrea; Bergheim, Ina; Machann, Jürgen; Schick, Fritz; Siegel-Axel, Dorothea; Schürmann, Annette; Weigert, Cora; Häring, Hans-Ulrich; Hennige, Anita M

    2014-01-01

    Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. Cinnamon components (eugenol, cinnamaldehyde) were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis.

  9. CONCENTRATION OF ARSENIC IN THE MUSCLE, LIVER AND KIDNEY OF CONSUMED CALVES IN THE WEST OF SYRIA

    Directory of Open Access Journals (Sweden)

    Ghiyath Soliman

    2016-11-01

    Full Text Available This study was conducted on 240 samples, 80 muscle, 80 kidney and 80 liver samples, which were collected from 80 calves’ carcasses (between 1-3 years old from Western Syria (Latakia, Tartus, Jableh and Safita. Samples were analyzed for the arsenic contamination using Atomic Absorption Spectrometry (AAS. The results showed that concentrations of arsenic in the kidney, liver and muscle of the calves in Latakia region were 0.7175, 0.602 and 0.4715 mg/kg, respectively. In Jableh region they were 0.43, 0.3425 and 0.2665 mg/kg, respectively, in Tartus region 0.5035, 0.4545 and 0.2918 mg/kg, respectively, and in Safita region 0.3615, 0.342 and 0.2168 mg/kg, respectively. Results also revealed that the highest arsenic concentration was detected in the kidney followed by liver and muscle, and was higher in the samples from Latakia and Tartus regions compared to the samples from Jableh and Safita regions.

  10. The Potential Liver, Brain, and Embryo Toxicity of Titanium Dioxide Nanoparticles on Mice

    Science.gov (United States)

    Jia, Xiaochuan; Wang, Shuo; Zhou, Lei; Sun, Li

    2017-08-01

    Nanoscale titanium dioxide (nano-TiO2) has been widely used in industry and medicine. However, the safety of nano-TiO2 exposure remains unclear. In this study, we evaluated the liver, brain, and embryo toxicity and the underlying mechanism of nano-TiO2 using mice models. The results showed that titanium was distributed to and accumulated in the heart, brain, spleen, lung, and kidney of mice after intraperitoneal (i.p.) nano-TiO2 exposure, in a dose-dependent manner. The organ/body weight ratios of the heart, spleen, and kidney were significantly increased, and those of the brain and lung were decreased. High doses of nano-TiO2 significantly damaged the functions of liver and kidney and glucose and lipid metabolism, as showed in the blood biochemistry tests. Nano-TiO2 caused damages in mitochondria and apoptosis of hepatocytes, generation of reactive oxygen species, and expression disorders of protective genes in the liver of mice. We found ruptured and cracked nerve cells and inflammatory cell infiltration in the brain. We also found that the activities of constitutive nitric oxide synthases (cNOS), inducible NOS (iNOS), and acetylcholinesterase, and the levels of nitrous oxide and glutamic acid were changed in the brain after nano-TiO2 exposure. Ex vivo mouse embryo models exhibited developmental and genetic toxicity after high doses of nano-TiO2. The size of nano-TiO2 particles may affect toxicity, larger particles producing higher toxicity. In summary, nano-TiO2 exhibited toxicity in multiple organs in mice after exposure through i.p. injection and gavage. Our study may provide data for the assessment of the risk of nano-TiO2 exposure on human health.

  11. Uptake of [3H]colchicine into brain and liver of mouse, rat, and chick

    International Nuclear Information System (INIS)

    Bennett, E.L.; Alberti, M.H.; Flood, J.F.

    1981-01-01

    The uptake of [ring A-4- 3 H] colchicine and [ring C-methoxy- 3 H]colchicine has been compared in mice from 1 to 24 hr after administration. Less radioactivity was found in brain after administration of ring-labeled colchicine than after administration of the methoxy-labeled colchicine. Three hr after administration of ring-labeled colchicine, 5% of the label was in liver and about 0.01% of the label was present in brain. Forty percent of the brain radioactivity was bound to tubulin as determined by vinblastine precipitation. After 3 hr, an average of 8% of the radioactivity from methoxy-labeled colchicine was found in the liver and 0.16% in brain. However, less than 5% of the activity in brain was precipitated by vinblastine, and the colchicine equivalent was comparable to that found after administration of the ring-labeled colchicine. The amount of colchicine entering mouse brain after subcutaneous injection is comparable to the minimum behaviorally effective dose when administered to the caudate. The metabolism of [ring C-methoxy- 3 H] and [ring A- 3 H]colchicine was also studied in rats. The general pattern was similar to mice; less radioactivity was found in brain after administration of the ring-labeled alkaloid than after administration of methoxy-labeled colchicine. Again, 40-50% of ring-labeled colchicine was precipitated by vinblastine. A much smaller percentage of the methoxy-labeled drug was precipitated by vinblastine than of the ring A-labeled colchicine. These experiments, together with behavioral experiments, support the hypotheses that structural alterations in synapses by recently synthesized proteins which are transported down the axons and dendrites may be an essential process for long-term memory formation

  12. UPTAKE OF [3H]-COLCHICINE INTO BRAIN AND LIVER OF MOUSE, RAT, AND CHICK

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Edward L.; Alberti, Marie Hebert; Flood, James F.

    1980-07-01

    The uptake of [ring A-4-{sup 3}H] colchicine and [ring C-methoxy-{sup 3}H]colchicine has been compared in mice from 1 to 24 hr after administration. Less radioactivity was found in brain after administration of ring-labeled colchicine than after administration of the methoxy-labeled colchicine. Three hr after administration of ring-labeled colchicine, 5% of the label was in liver and about 0.01% of the label was present in brain. Forty percent of the brain radioactivity was bound to tubulin as determined by vinblastine precipitation. After 3 hr, an average of 8% of the radioactivity from methoxy-labeled colchicine was found in the liver and 0.16% in brain. However, less than 5% of the activity in brain was precipitated by vinblastine, and the colchicine equivalent was comparable to that found after administration of the ring-labeled colchicine. The amount of colchicine entering mouse brain after subcutaneous injection is comparable to the minimum behaviorally effective dose when administered to the caudate. The metabolism of [ring C-methoxy-{sup 3}H] and [ring A-{sup 3}H]colchicine was also studied in rats. the general pattern was similar to mice; less radioactivity was found in brain after administration of the ring-labeled alkoloid than after administration of methoxy-labeled colchicine. Again, 40-50% of ring-labeled colchicine was precipitated by vinblastine. A much smaller percentage of the methoxy-labeled drug was precipitated by vinblastine than of the ring A-labeled colchicine. These experiments, together with behavioral experiments [7], support the hypotheses that structural alteration in synapses by recently synthesized proteins which are transported down the axons and dendrites may be an essential process for long-term memory formation.

  13. The significance of alteration 2-[fluorine-18]fluoro-2-deoxy-(D)-glucose uptake in the liver and skeletal muscles of patients with hyperthyroidism.

    Science.gov (United States)

    Chen, Yen-Kung; Chen, Yen-Ling; Tsui, Chih-Cheng; Wang, Su-Chen; Cheng, Ru-Hwa

    2013-10-01

    Hyperthyroidism leads to an enhanced demand for glucose. The hypothesis of the study is that 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) can demonstrate the alteration of systemic glucose metabolism in hyperthyroidism patients by measuring the FDG standard uptake value (SUV) in liver and skeletal muscle. Forty-eight active hyperthyroidism patients and 30 control participants were recruited for the study. The intensity of FDG uptake in the liver and thigh muscles was graded subjectively, comprising three groups: group I, higher FDG uptake in the liver; group II, equal FDG uptake in the liver and muscles; and group III, higher FDG uptake in the muscles. Ten subjects with FDG PET scans at hyperthyroid and euthyroid status were analyzed. Serum levels of thyroxine (T4) and triiodothyronine (T3) correlated to the SUVs of the liver and muscles. Forty-one patients (41/48, 85.4%) showed symmetrically increased FDG uptake in the muscles (22 in group I, 9 in group II, and 17 in group III). Group I patients were significantly older than group II (P = .02) and group III (P = .001) patients. The correlation coefficient between the serum T3, T4, and SUV levels in the muscles was significant (r = 0.47-0.77, P hyperthyroid and euthyroid states. In the 30 control subjects, there was normal physiological FDG uptake in the liver and muscles. In PET scans showing a pattern of decreased liver and increased skeletal muscle FDG uptake in hyperthyroidism patients, this change of FDG distribution is correspondence to the severity of hyperthyroidism status. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  14. Respiration and substrate transport rates as well as reactive oxygen species production distinguish mitochondria from brain and liver.

    Science.gov (United States)

    Gusdon, Aaron M; Fernandez-Bueno, Gabriel A; Wohlgemuth, Stephanie; Fernandez, Jenelle; Chen, Jing; Mathews, Clayton E

    2015-09-10

    Aberrant mitochondrial function, including excessive reactive oxygen species (ROS) production, has been implicated in the pathogenesis of human diseases. The use of mitochondrial inhibitors to ascertain the sites in the electron transport chain (ETC) resulting in altered ROS production can be an important tool. However, the response of mouse mitochondria to ETC inhibitors has not been thoroughly assessed. Here we set out to characterize the differences in phenotypic response to ETC inhibitors between the more energetically demanding brain mitochondria and less energetically demanding liver mitochondria in commonly utilized C57BL/6J mice. We show that in contrast to brain mitochondria, inhibiting distally within complex I or within complex III does not increase liver mitochondrial ROS production supported by complex I substrates, and liver mitochondrial ROS production supported by complex II substrates occurred primarily independent of membrane potential. Complex I, II, and III enzymatic activities and membrane potential were equivalent between liver and brain and responded to ETC. inhibitors similarly. Brain mitochondria exhibited an approximately two-fold increase in complex I and II supported respiration compared with liver mitochondria while exhibiting similar responses to inhibitors. Elevated NADH transport and heightened complex II-III coupled activity accounted for increased complex I and II supported respiration, respectively in brain mitochondria. We conclude that important mechanistic differences exist between mouse liver and brain mitochondria and that mouse mitochondria exhibit phenotypic differences compared with mitochondria from other species.

  15. Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism

    Science.gov (United States)

    Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Mukai, David; Patterson, Steven E.; Boss, Gerry R.; Tromberg, Bruce J.; Brenner, Matthew

    2012-10-01

    Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

  16. Sex-specific differences in transcriptome profiles of brain and muscle tissue of the tropical gar.

    Science.gov (United States)

    Cribbin, Kayla M; Quackenbush, Corey R; Taylor, Kyle; Arias-Rodriguez, Lenin; Kelley, Joanna L

    2017-04-07

    The tropical gar (Atractosteus tropicus) is the southernmost species of the seven extant species of gar fishes in the world. In Mexico and Central America, the species is an important food source due to its nutritional quality and low price. Despite its regional importance and increasing concerns about overexploitation and habitat degradation, basic genetic information on the tropical gar is lacking. Determining genetic information on the tropical gar is important for the sustainable management of wild populations, implementation of best practices in aquaculture settings, evolutionary studies of ancient lineages, and an understanding of sex-specific gene expression. In this study, the transcriptome of the tropical gar was sequenced and assembled de novo using tissues from three males and three females using Illumina sequencing technology. Sex-specific and highly differentially expressed transcripts in brain and muscle tissues between adult males and females were subsequently identified. The transcriptome was assembled de novo resulting in 80,611 transcripts with a contig N50 of 3,355 base pairs and over 168 kilobases in total length. Male muscle, brain, and gonad as well as female muscle and brain were included in the assembly. The assembled transcriptome was annotated to identify the putative function of expressed transcripts using Trinotate and SwissProt, a database of well-annotated proteins. The brain and muscle datasets were then aligned to the assembled transcriptome to identify transcripts that were differentially expressed between males and females. The contrast between male and female brain identified 109 transcripts from 106 genes that were significantly differentially expressed. In the muscle comparison, 82 transcripts from 80 genes were identified with evidence for significant differential expression. Almost all genes identified as differentially expressed were sex-specific. The differentially expressed transcripts were enriched for genes involved in

  17. Magnetic resonance imaging (MRI) of liver and brain in haematologic-organic patients with fever of unknown origin

    International Nuclear Information System (INIS)

    Heussel, C.P.; Kauczor, H.U.; Poguntke, M.; Schadmand-Fischer, S.; Mildenberger, P.; Thelen, M.; Heussel, G.

    1998-01-01

    To examine the advantage of liver and brain MRI in clinically anomalous haematological patients with fever of unknown origin. Material and Methods: Twenty liver MRI (T 2 -TSE, T 2 -HASTE, T 1 -FLASH±Gd dynamic) and 16 brain MRI (T 2 -TSE, FLAIR, T 1 -TSE±Gd) were performed searching for a focus of fever with a suspected organ system. Comparison with clinical follow-up. Results: suspected organ system. Comparison with clinical follow-up. Results: A focus was detected in 11/20 liver MRI. Candidiasis (n=3), mycobacteriosis (n=2), relapse of haematological disease (n=3), graft versus host disease (n=1), non-clarified (n=2). The remaining 9 cases with normal MRI were not suspicious of infectious hepatic disease during follo-wup. In brain MRI, 3/16 showed a focus (toxoplasmosis, aspergillosis, mastoiditis). Clinical indication for an infectious involvement of the brain was found in 4/16 cases 2--5 months after initially normal brain MRI. No suspicion of an infectious involvement of brain was present in the remaining 9/16 cases. Conclusion: In case of fever of unknown origin and suspicion of liver involvement, MRI of the liver should be performed due to data given in literature and its sensitivity of 100%. Because of the delayed detectability of cerebral manifestations, in cases of persisting suspicion even a previously normal MRI of the brain should be repeated. (orig.) [de

  18. Increased blood-brain transfer in a rabbit model of acute liver failure

    International Nuclear Information System (INIS)

    Horowitz, M.E.; Schafer, D.F.; Molnar, P.; Jones, E.A.; Blasberg, R.G.; Patlak, C.S.; Waggoner, J.; Fenstermacher, J.D.

    1983-01-01

    The blood-to-brain transfer of [ 14 C]alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of [ 14 C]alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of [ 14 C]galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy

  19. Effect of thiamine deficiency, pyrithiamine and oxythiamine on pyruvate metabolism in rat liver and brain in vivo

    International Nuclear Information System (INIS)

    Meghal, S.K.; O'Neal, R.M.; Koeppe, R.E.

    1977-01-01

    Rats were fed either a thiamine-deficient diet or diets containing pyrithiamine or oxythiamine. When symptoms of thiamine deficiency appeared, the animals were injected intraperitoneally with [2- 14 C] pyruvate six to twelve minutes prior to sacrifice. Free glutamic and aspartic acids were isolated from liver and brain and degraded. The results indicate that, in thiamine-deficient or oxythiamine-treated rats, pyruvate metabolism in liver and brain is similar to that in normal animals. In contrast, pyrithinamine drastically decreases the oxidative decarboxylation of pyruvate by rat liver. (auth.)

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

    Science.gov (United States)

    Narsale, Aditi A; Puppa, Melissa J; Hardee, Justin P; VanderVeen, Brandon N; Enos, Reilly T; Murphy, E Angela; Carson, James A

    2016-09-13

    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.

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

    Science.gov (United States)

    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

  2. Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Q. [Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Shandong University, Jinan (China); Wang, L.X. [Department of Pharmacology, School of Medicine, Shandong University, Jinan (China); Zeng, J.P. [Department of Biochemistry, School of Medicine, Shandong University, Jinan (China); Liu, X.J.; Liang, X.M.; Zhou, Y.B. [Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Shandong University, Jinan (China)

    2013-09-06

    Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis.

  3. Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers

    International Nuclear Information System (INIS)

    Wang, Q.; Wang, L.X.; Zeng, J.P.; Liu, X.J.; Liang, X.M.; Zhou, Y.B.

    2013-01-01

    Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis

  4. Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in experimental acute liver failure.

    Science.gov (United States)

    Rama Rao, Kakulavarapu V; Verkman, A S; Curtis, Kevin M; Norenberg, Michael D

    2014-03-01

    Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6% ± 0.3 and 2.3 ± 0.4%, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. Published by Elsevier Inc.

  5. 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.

    Science.gov (United States)

    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.

  6. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

    Science.gov (United States)

    Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

    2011-04-01

    Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  7. Metal levels in blood, muscle and liver of water snakes (Nerodia spp.) from New Jersey, Tennessee and South Carolina

    Energy Technology Data Exchange (ETDEWEB)

    Burger, Joanna [Division of Life Sciences, Nelson Biological Lab., Rutgers Univ., 604 Allison Road, Piscataway, New Jersey (United States)]|[Consortium for Risk Evaluation with Stakeholder Participation and Environmental and Occupational Health Sciences Inst., Piscataway, New Jersey (United States)]. E-mail: burger@biology.rutgers.edu; Campbell, Kym Rouse [Consortium for Risk Evaluation with Stakeholder Participation, and Environmental and Occupational Health Sciences Inst., Piscataway, New Jersey (United States)]|[Biological Research Associates, 3910 U.S. Highway 301 North, Suite 180, Tampa, Florida 33619 (United States); Murray, Stephanie; Jeitner, Christian; Burke, Sean [Div. of Life Sciences, Nelson Biological Lab., Rutgers Univ., 604 Allison Road, Piscataway, New Jersey (United States)]|[Consortium for Risk Evaluation with Stakeholder Participation, and Environmental and Occupational Health Sciences Inst., Piscataway, New Jersey (United States); Campbell, Todd S. [Consortium for Risk Evaluation with Stakeholder Participation, and Environmental and Occupational Health Sciences Inst., Piscataway, New Jersey (United States)]|[Dept. of Biology, Box 3F, Univ. of Tampa, 401 West Kennedy Boulevard, Tampa, Florida 33606-1490 (United States); Gaines, Karen F. [Consortium for Risk Evaluation with Stakeholder Participation, and Environmental and Occupational Health Sciences Inst., Piscataway, New Jersey (United States)]|[Savannah River Ecology Lab., Univ. of Georgia, P.A. Drawer E, Aiken, South Carolina 29802 (United States)]|[Dept. of Biology, Univ. of South Dakota, 414 E. Clark St., Vermillion, South Dakota 57069 (United States); Shukla, Tara; Gochfeld, Michael [Consortium for Risk Evaluation with Stakeholder Participation, and Environmental and Occupational Health Sciences Inst., Piscataway, New Jersey (United States)]|[Environmental and Occupational Medicine, UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey (United States)

    2007-02-15

    Reptiles, particularly snakes, could serve as bioindicators of contamination because some are comparatively long-lived, exhibit different trophic levels, and are at the top of their food chains. We test the null hypothesis that there are no differences in the concentrations of heavy metals in the blood, muscle and liver of water snakes (Nerodia spp.) from rivers in New Jersey, Tennessee and South Carolina. While the former site is in an urban/suburban area, the latter two sites are relatively rural and are located on Department of Energy sites. For the snakes from New Jersey, there were significant differences in metal concentrations among tissues for all metals, the highest levels for arsenic and selenium were in liver and kidney, for cadmium were in the liver, for chromium and lead were in skin, and for mercury and manganese were in the muscle. Body length was not correlated with metal levels, and there were more significant correlations for skin with internal tissues than for blood with other tissues. There were more significant correlations for mercury than for other metals. In comparing metal levels among states, levels were generally higher for snakes collected from South Carolina. These data indicate that, since water snakes accumulate contaminants differentially as a function of location, they can be useful bioindicators of environmental exposure to contaminants. Moreover, because of their wide geographical distribution and use of varying trophic compartments, this genus can be useful for cross-site comparisons.

  8. Virtual determination of liver and muscle glycogen obtained from fed rats and from 24-hour fasted rats

    Directory of Open Access Journals (Sweden)

    V.M.T.T. Trindidade et al

    2014-08-01

    Full Text Available Introduction: Glycogen is the storage polysaccharide of animals, composed by glucoseresidues forming a branched polymer. The liver glycogen metabolism and hepaticgluconeogenesis are important buffer systems of blood glucose in different physiological orpathological situations, such as, during a fast period. Fasting muscle glycogenolysis alsooccurs, however, the release of glucose into the bloodstream is negligible because themuscle doesn’t have the enzyme glucose-6-P phosphatase, which is present in the liver.Objectives: This panel presents a learning object, mediated by computer, which simulatesthe determination of liver and muscle glycogen obtained from fed rats and from 24-hourfasted rats Materials and Methods: At first, cartoons were planned in order to show themethodology procedures and biochemical fundamentals. The most representative imageswere selected, edited, organized in a scene menu and inserted into an animationdeveloped with the aid of the Adobe ® Flash 8 software. The validation of this object wasperformed by the students of Biochemistry I (Pharmacy-UFRGS from the secondsemester of 2009 until the second semester of 2013. Results and Discussion: Theanalysis of students' answers revealed that 83% of them attributed the excellence rate tothe navigation program, to the display format and to the learning help. Conclusion:Therefore, this learning object can be considered an adequate teaching resource as wellas an innovative support in the construction of theoretical and practical knowledge ofBiochemistry. Support: SEAD-UFRGSAvailable at: http://www.ufrgs.br/gcoeb/obtencaodosagemglicogenio/

  9. Effect of Heavy Metals on Liver, Kidney, Gills and Muscles of Cyprinus carpio and Wallago attu inhabited in the Indus

    Directory of Open Access Journals (Sweden)

    Shahid Mahboob

    Full Text Available ABSTRACT: The present study was aimed to evaluate the effect of heavy metals on an important tissue of two fish species Cyprinus carpio and Wallago attu, sampled from the Indus river, Mianwali District, Pakistan. The concentration of selected heavy metals Fe, Cr, Cu, and in gills, muscles, kidney and liver was compared with an International standard of food fish. The overall metal concentrations among different weight categories in C. carpio were in the order of Fe > Cu > Cr >. In W. attu the overall accumulation of these metals were, in order of Fe > Cu > Cr > Pb The order of accumulation of metals in gills and muscle of C. carpio was Fe > Cr > Pb > Cu; kidney and muscles of W. attu was Fe > Cr > Cu > Pb; liver Fe > Cu > Cr > Pb. An increasing trend of concentration of iron, copper, chromium and lead occurred with an increase in weight of C. carpio and W. attu. There was a significant difference in the accumulation of heavy metals in different organs of both species (p<0.01. All studied heavy metals except Cr were within permissible limits described by various international agencies like WHO, FAO and FEPA in edible tissues of C. carpio and W. attu.

  10. Influence of ontogeny and environmental exposure on mercury accumulation in muscle and liver of male Round Stingrays.

    Science.gov (United States)

    Lyons, Kady; Carlisle, Aaron B; Lowe, Christopher G

    2017-09-01

    Mercury tissue distribution and its dynamics are poorly understood in elasmobranchs. Total mercury was measured in liver and muscle of male Round Stingrays (Urobatis halleri) from Seal Beach, California, an anthropogenically impacted site, and from the offshore island of Santa Catalina, a less impacted site. Stable isotope analysis was also performed on the muscle and red blood cells (RBCs) of a subset of rays over a range of age classes to investigate mercury accumulation with respect to trophic ecology. Mercury in both tissues was found to be significantly greater in adults than juveniles in mainland rays; however, liver mercury accumulation drastically increased after maturity and was significantly greater in mainland adult rays than Catalina rays. There were no patterns in δ 15 N or δ 13 C with size in muscle; however, there were indications of seasonal changes in RBC δ 15 N, suggesting short term shifts in diet or behavior is likely linked to reproductive status as is mercury accumulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Thomas Loyau

    Full Text Available 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.

  12. Determination of Florfenicol Residues in the Muscle and Liver of Cultured Rainbow Trout in Iran by ELISA

    Directory of Open Access Journals (Sweden)

    Firooz Fadaeifard

    2015-09-01

    Full Text Available Florfenicol is a broad-spectrum antibiotic, widely used in veterinary medicine. The aim of this study was to determine florfenicol residues in the muscle and liver of cultured rainbow trout in Iran by ELISA. The samples were collected from three areas (Kiar, Ardal, and Koohrang, considered as areas with high production of trout in the western part of Iran. Sampling was completed during the spring and summer of 2011. All of the samples were categorized into three weight groups (below 50g, 50 to150g and over 150g and five individuals were randomly selected from fish belonged to each weigh group, and then collected samples sent for determination of antibiotic residues. The highest and the lowest antibiotic residues were 31.42±53.52 ng g-1 (>150 g fish and 10.35±2.33 ng g-1 (<50 g fish for liver samples and 48.84±50.36 ng g-1 (50-150 g fish and 18.20±15.41 ng g-1 (> 150 g fish for muscle samples, respectively. In different areas, the highest antibiotic levels were found in Koohrang and Ardal with mean of 37.00±63.61 and 15.33±10.45 ng g-1 for liver samples and 40.74±40.80 and 28.24±45.91ng g-1 for muscle samples. The results indicated that florfenicol residues are lower than the maximum permissible level has been announced by the European Union.

  13. Nonparenchymal cells cultivated from explants of fibrotic liver resemble endothelial and smooth muscle cells from blood vessel walls

    International Nuclear Information System (INIS)

    Voss, B.; Rauterberg, J.; Pott, G.; Brehmer, U.; Allam, S.; Lehmann, R.; von Bassewitz, D.B.

    1982-01-01

    Tissue specimens from human fibrotic liver obtained by needle biopsy were cultured. Two cell types emerged from the tissue explants. From their morphology and biosynthetic products they resembled smooth muscle cells and endothelial cells from blood vessel walls. In the endothelial cells, factor VIII-associated protein was demonstrated by indirect immunofluorescence. Synthesis of collagen types I and III, basement membrane collagen types IV and V, and fibronectin by both cell types was observed by immunofluorescence microscopy. Homogeneous cultures of smooth muscle cells were observed in subcultures. After incubation with [ 14 C]glycine, collagen was isolated and characterized by CM cellulose chromatography, and consisted mainly of types I and III. These data suggest involvement of mesenchymal cells in hepatic fibrosis; they presumably originate from blood vessel or sinusoidal walls

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

    Science.gov (United States)

    Koch, Franziska; Lamp, Ole; 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

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

    Science.gov (United States)

    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

  16. Expression of alcoholism-relevant genes in the liver are differently correlated to different parts of the brain.

    Science.gov (United States)

    Wang, Lishi; Huang, Yue; Jiao, Yan; Chen, Hong; Cao, Yanhong; Bennett, Beth; Wang, Yongjun; Gu, Weikuan

    2013-01-01

    The purpose of this study is to investigate whether expression profiles of alcoholism-relevant genes in different parts of the brain are correlated differently with those in the liver. Four experiments were conducted. First, we used gene expression profiles from five parts of the brain (striatum, prefrontal cortex, nucleus accumbens, hippocampus, and cerebellum) and from liver in a population of recombinant inbred mouse strains to examine the expression association of 10 alcoholism-relevant genes. Second, we conducted the same association analysis between brain structures and the lung. Third, using five randomly selected, nonalcoholism-relevant genes, we conducted the association analysis between brain and liver. Finally, we compared the expression of 10 alcoholism-relevant genes in hippocampus and cerebellum between an alcohol preference strain and a wild-type control. We observed a difference in correlation patterns in expression levels of 10 alcoholism-relevant genes between different parts of the brain with those of liver. We then examined the association of gene expression between alcohol dehydrogenases (Adh1, Adh2, Adh5, and Adh7) and different parts of the brain. The results were similar to those of the 10 genes. Then, we found that the association of those genes between brain structures and lung was different from that of liver. Next, we found that the association patterns of five alcoholism-nonrelevant genes were different from those of 10 alcoholism-relevant genes. Finally, we found that the expression level of 10 alcohol-relevant genes is influenced more in hippocampus than in cerebellum in the alcohol preference strain. Our results show that the expression of alcoholism-relevant genes in liver is differently associated with the expression of genes in different parts of the brain. Because different structural changes in different parts of the brain in alcoholism have been reported, it is important to investigate whether those structural differences in

  17. Insights into Brain Glycogen Metabolism

    Science.gov (United States)

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-01-01

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  18. Quantification of the glycogen cascade system: the ultrasensitive responses of liver glycogen synthase and muscle phosphorylase are due to distinctive regulatory designs

    Directory of Open Access Journals (Sweden)

    Venkatesh KV

    2005-05-01

    Full Text Available Abstract Background Signaling pathways include intricate networks of reversible covalent modification cycles. Such multicyclic enzyme cascades amplify the input stimulus, cause integration of multiple signals and exhibit sensitive output responses. Regulation of glycogen synthase and phosphorylase by reversible covalent modification cycles exemplifies signal transduction by enzyme cascades. Although this system for regulating glycogen synthesis and breakdown appears similar in all tissues, subtle differences have been identified. For example, phosphatase-1, a dephosphorylating enzyme of the system, is regulated quite differently in muscle and liver. Do these small differences in regulatory architecture affect the overall performance of the glycogen cascade in a specific tissue? We address this question by analyzing the regulatory structure of the glycogen cascade system in liver and muscle cells at steady state. Results The glycogen cascade system in liver and muscle cells was analyzed at steady state and the results were compared with literature data. We found that the cascade system exhibits highly sensitive switch-like responses to changes in cyclic AMP concentration and the outputs are surprisingly different in the two tissues. In muscle, glycogen phosphorylase is more sensitive than glycogen synthase to cyclic AMP, while the opposite is observed in liver. Furthermore, when the liver undergoes a transition from starved to fed-state, the futile cycle of simultaneous glycogen synthesis and degradation switches to reciprocal regulation. Under such a transition, different proportions of active glycogen synthase and phosphorylase can coexist due to the varying inhibition of glycogen-synthase phosphatase by active phosphorylase. Conclusion The highly sensitive responses of glycogen synthase in liver and phosphorylase in muscle to primary stimuli can be attributed to distinctive regulatory designs in the glycogen cascade system. The different

  19. Integrated response of antioxidant biomarkers in the liver and white muscle of European hake (Merluccius merluccius L. females from the Adriatic sea with respect to environmental influences

    Directory of Open Access Journals (Sweden)

    Pavlović Slađan Z.

    2018-01-01

    Full Text Available We investigated the integrated response of antioxidant defense enzymes (total superoxide dismutase (TotSOD, manganese-containing superoxide dismutase (MnSOD, copper-zinc-containing superoxide dismutase (CuZnSOD, catalase (CAT, glutathione peroxidase (GSH-Px, glutathione reductase (GR and phase II biotransformation enzyme, glutathione- S-transferase (GST in the liver and white muscle of females of European hake (Merluccius merluccius L. from the Adriatic Sea (Montenegro in winter and spring. The activity of GSH-Px in the liver was significantly increased, while GST activity was decreased in spring compared to the winter. In white muscle, the activities of TotSOD and CuZnSOD were increased, while the activities of MnSOD, CAT, GSH-Px, GR and GST were decreased in spring when compared to the matching values in winter. The activities of TotSOD and CuZnSOD in winter were markedly lower in the muscle than in the liver, while the activity of MnSOD in the muscle was higher when compared to the liver. Principal component analysis (PCA revealed clear separation of the investigated antioxidant biomarkers between tissues and seasons, while the integrated biomarker response (IBR showed that the most intensive antioxidant biomarker response was in the liver in spring. Star plots of IBR showed a dominant contribution of glutathione-dependent biomarkers (GSH-Px, GR and GST and CAT in both tissues and seasons with respect to SOD isoenzymes. All enzyme activities (except MnSOD were greater in the liver in comparison to the white muscle. Our results show that the liver possesses a greater capacity to establish and maintain homeostasis under changing environmental conditions in winter and spring. At the same time, seasonal effects are more pronounced in muscle tissue. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173041

  20. Liver

    International Nuclear Information System (INIS)

    Bernardino, M.E.; Sones, P.J. Jr.; Barton Price, R.; Berkman, W.A.

    1984-01-01

    Evaluation of the liver for focal lesions is extremely important because the liver is one of the most common sites for metastatic disease. Most patients with metastatic deposits to the liver have a survival rate of about 6 months. Thus, metastatic disease to the liver has an extremely grave prognosis. In the past patients with hepatic lesions had no therapeutic recourse. However, with recent aggressive surgical advances (such as partial hepatectomies) and hepatic artery embolization, survival of patients with hepatic metastases has increased. Thus it is important for noninvasive imaging not only to detect lesions early in their course, but also to give their true hepatic involvement and the extent of the neoplastic process elsewhere in the body. Recent advances in imaging have been rapidly changing over the past 5 years. These changes have been more rapid in computed tomography (CT) and ultrasound than in radionuclide imaging. Thus, the question addressed in this chapter is: What is the relationship of hepatic ultrasound to the other current diagnostic modalities in detecting metastatic liver disease and other focal liver lesions? Also, what is its possible future relationship to nuclear magnetic resonance?

  1. Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

    Science.gov (United States)

    Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

    2016-08-01

    This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline.

  2. The state of glutathion system of blood, brain and liver of white rats after chronic gamma-irradiation

    International Nuclear Information System (INIS)

    Petushok, N.Eh.; Lashak, L.K.; Trebukhina, R.V.

    1999-01-01

    The effects of 3-fold gamma-irradiation in total dose 0,75 Gy on the glutathion system in different periods after exposure (1 hour, 1 day, 1 and 4 weeks) in blood, brain and liver of white rats were studied. It was concluded that liver and brain have higher ability to maintain the stability of antioxidant system than blood has. After shot disturbances caused by irradiation in brain and liver the state of glutathion system of detoxication has normalized, while concentration of malonic dialdehyde was raised in all terms. The most pronounced changes of antioxidant system were registered in blood at early terms (1 hour) after irradiation that was manifested in increasing of reduced glutathion content, raising of glutathion reductase and catalase activity. In remote period the activity of this system in blood was exhausted

  3. Insulin signaling in skeletal muscle and liver of neonatal pigs during endotoxemia

    Science.gov (United States)

    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...

  4. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

    Directory of Open Access Journals (Sweden)

    Katarzyna Bozek

    2014-05-01

    Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

  5. Interaction of red pepper (Capsicum annum, Tepin) polyphenols with Fe(II)-induced lipid peroxidation in brain and liver

    Energy Technology Data Exchange (ETDEWEB)

    Oboh, G [Biochemistry Department, Federal University of Technology, Akure, Ondo State (Nigeria); [Departamento de Quimica, Universidade Federal de Santa Maria (UFSM), Campus Universitario - Camobi, Santa Maria RS (Brazil); [Abdus Salam International Centre for Theoretical Physics, Trieste (Italy)]. E-mail: goboh2001@yahoo.com; Rocha, J B.T. [Campus Universitario - Camobi, Santa Maria RS (Brazil)

    2006-03-15

    Polyphenols exhibit a wide range of biological effects because of their antioxidant properties. Several types of polyphenols (phenolic acids, hydrolyzable tannins, and flavonoids) show anticarcinogenic and antimutagenic effects. Comparative studies were carried on the protective ability of free and bound polyphenol extracts of red Capsicum annuum Tepin (CAT) on brain and liver - In vitro. Free polyphenols of red Capsicum annuum Tepin (CAT) were extracted with 80% acetone, while the bound polyphenols were extracted with ethyl acetate from acid and alkaline hydrolysis of the pepper residue from free polyphenols extract. The phenol content, Fe (II) chelating ability, OH radical scavenging ability and protective ability of the extract against Fe (II)-induced lipid peroxidation in brain and liver was subsequently determined. The results of the study revealed that the free polyphenols (218.2mg/100g) content of the pepper were significantly higher than the bound polyphenols (42.5mg/100g). Furthermore, the free polyphenol extract had a significantly higher (<0.05) Fe (II) chelating ability, OH radical scavenging ability than the bound polyphenols. In addition, both extracts significantly inhibited (P<0.05) basal and 25{mu}M Fe (II)- induced lipid peroxidation in Rat's brain and liver in a dose dependent. However, the free polyphenols caused a significantly higher inhibition in the MDA (Malondialdehyde) production in the brain and liver homogenates than the bound phenols. Furthermore, the polyphenols protected the liver more than the brain. In conclusion, free polyphenols from Capsicum annuum protects both the liver and brain from Fe{sup 2+} induced lipid peroxidation, and this is probably due to the higher Fe (II) chelating ability and OH radical scavenging ability of the free polyphenols from the pepper. (author)

  6. Muscle and liver protein synthesis in growing rats fed diets containing raw legumes as the main source of protein

    International Nuclear Information System (INIS)

    Goena, M.; Santidrian, S.; Cuevillas, F.; Larralde, J.

    1986-01-01

    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-/ 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

  7. Influence of the dietary protein deficiency on the activities of ribosomes and polysome patterns in muscle and liver of rats

    International Nuclear Information System (INIS)

    Goto, Akihiko; Kametaka, Masao

    1975-01-01

    A group of rats weighing about 120 g were killed at the beginning of the experiment and after 10 days on the 20% casein diet (C-0 and C-10 groups), and another group of rats were killed after 1,2 and 10 days on the protein-free diet (PF-1, PF-2 and PF-10 groups). From muscle and the liver of each group ribosomes were prepared, and the protein synthesis activity and the polysome patterns were investigated. The activity of polysome fractionated into each size was also measured. Muscle ribosome activity in PF-1, PF-2 and PF-10 groups decreased to about 60%, 40% and 40% of that in C groups, respectively, and this decrease was due to a fall in activity of prolysome itself rather than disaggregation of polysome. Liver ribosome activity in PF-1, PF-2 and PF-10 groups were reduced to about 95%, 90% and 65% of that in C groups, respectively. These alterations in PF-1 and PF-2 groups seemed to be in part related to changes in polysome pattern, whereas ribosome activity in PF-10 group was reduced without changes in polysome pattern. (auth.)

  8. Gestational protein restriction in mice has pronounced effects on gene expression in newborn offspring's liver and skeletal muscle; protective effect of taurine

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Olsen, Hanne Lodberg; Frandsen, Lis

    2010-01-01

    We examined gene expression changes in liver and skeletal muscle of newborn mice subjected to a maternal low protein (LP) or normal protein (NP) diet during pregnancy, with or without taurine supplementation in the drinking water. LP offspring had a 40% lower birthweight than NP offspring, whereas...... it was reduced by only 20% with taurine supplementation. Microarray gene expression analysis revealed significant changes in 2012 genes in liver and 967 genes in skeletal muscle of LP offspring. By unknown mechanisms, taurine partially or fully prevented 30 and 46% of these expression changes, respectively....... Mitochondrial genes, in particular genes associated with oxidative phosphorylation, were more abundantly changed in LP offspring, with primarily up-regulation in liver but down-regulation in skeletal muscle. In both tissues, citrate synthase activity remained unchanged. Taurine preferentially rescued changes...

  9. Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.

    Directory of Open Access Journals (Sweden)

    Wen Miao

    Full Text Available To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1 patients using multimodal MRI imaging.T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls.Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (p<0.001 uncorrected in the left precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus.CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1.

  10. Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.

    Science.gov (United States)

    Miao, Wen; Man, Fengyuan; Wu, Shaoqin; Lv, Bin; Wang, Zhenchang; Xian, Junfang; Sabel, Bernhard A; He, Huiguang; Jiao, Yonghong

    2015-01-01

    To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1) patients using multimodal MRI imaging. T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls. Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (pleft precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus. CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1.

  11. Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study

    Science.gov (United States)

    Wu, Shaoqin; Lv, Bin; Wang, Zhenchang; Xian, Junfang; Sabel, Bernhard A.; He, Huiguang; Jiao, Yonghong

    2015-01-01

    Purpose To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1) patients using multimodal MRI imaging. Methods T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender- matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls. Results Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (pleft precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus. Conclusions CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1. PMID:26186732

  12. Variation in metabolic enzymatic activity in white muscle and liver of blue tilapia, Oreochromis aureus, in response to long-term thermal acclimatization

    Science.gov (United States)

    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.

  13. Differential regulation of PGC-1α expression in rat liver and skeletal muscle in response to voluntary running

    Directory of Open Access Journals (Sweden)

    Azhar Salman

    2010-04-01

    Full Text Available Abstract Background The beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1α. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1α protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid metabolism. Methods Two groups of male Wistar rats (2 Mo of age, 188.82 ± 2.77 g BW were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1α protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations. Results Rats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean ± SE of 4.102 ± 0.747 km/day and consumed significantly more food as compared to sedentary controls (P P P P Conclusion These data suggest that PGC-1α most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity and lowering of circulating FFA levels.

  14. Effects of Lactobacillus feed supplementation on cholesterol, fat content and fatty acid composition of the liver, muscle and carcass of broiler chickens

    OpenAIRE

    Renseigné , Non; Abdullah , Norhani; Jalaludin , Syed; C.V.L. Wong , Michael; Yin Wan Ho ,

    2006-01-01

    International audience; An experiment was conducted to study the effects of feed supplementation with a mixture of Lactobacillus cultures (LC) on cholesterol, fat and fatty acid composition in the liver, muscle and carcass of broiler chickens. One hundred and thirty-six, one-day-old male broiler chicks (Avian-43) were assigned randomly to two dietary treatments: (i) a basal diet (control), and (ii) a basal diet + 0.1% LC. The cholesterol contents of the carcass and liver but not the muscle, w...

  15. The comparison of lipid profiling in mouse brain and liver after starvation and a high-fat diet: A medical systems biology approach

    NARCIS (Netherlands)

    Ginneken, V.J.T. van; Verheij, E.; Hekman, M.; Greef, J. van der; Feskens, E.J.M.; Poelmann, R.E.

    2011-01-01

    We investigated with LC-MS techniques, measuring approximately 109 lipid compounds, in mouse brain and liver tissue after 48 hours of starvation and a High-Fat Diet if brain and liver lipid composition changed. We measured Cholesterolesters (ChE), Lysophosphatidyl-cholines (LPC), Phosphatidylcholine

  16. Gestational age dependent changes of the fetal brain, liver and adipose tissue fatty acid compositions in a population with high fish intakes

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Offringa, Pieter J.; Boersma, E. Rudy; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2012-01-01

    Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes. Subjects and methods: We analyzed the brain (n = 18), liver (n = 14) and adipose tissue (n = 11) FA compositions of 20 stillborn

  17. Zebrafish: a model animal for analyzing the impact of environmental pollutants on muscle and brain mitochondrial bioenergetics.

    Science.gov (United States)

    Bourdineaud, Jean-Paul; Rossignol, R; Brèthes, D

    2013-01-01

    Mercury, anthropogenic release of uranium (U), and nanoparticles constitute hazardous environmental pollutants able to accumulate along the aquatic food chain with severe risk for animal and human health. The impact of such pollutants on living organisms has been up to now approached by classical toxicology in which huge doses of toxic compounds, environmentally irrelevant, are displayed through routes that never occur in the lifespan of organisms (for instance injecting a bolus of mercury to an animal although the main route is through prey and fish eating). We wanted to address the effect of such pollutants on the muscle and brain mitochondrial bioenergetics under realistic conditions, at unprecedented low doses, using an aquatic model animal, the zebrafish Danio rerio. We developed an original method to measure brain mitochondrial respiration: a single brain was put in 1.5 mL conical tube containing a respiratory buffer. Brains were gently homogenized by 13 strokes with a conical plastic pestle, and the homogenates were immediately used for respiration measurements. Skinned muscle fibers were prepared by saponin permeabilization. Zebrafish were contaminated with food containing 13 μg of methylmercury (MeHg)/g, an environmentally relevant dose. In permeabilized muscle fibers, we observed a strong inhibition of both state 3 mitochondrial respiration and cytochrome c oxidase activity after 49 days of MeHg exposure. We measured a dramatic decrease in the rate of ATP release by skinned muscle fibers. Contrarily to muscles, brain mitochondrial respiration was not modified by MeHg exposure although brain accumulated twice as much MeHg than muscles. When zebrafish were exposed to 30 μg/L of waterborne U, the basal mitochondrial respiratory control ratio was decreased in muscles after 28 days of exposure. This was due to an increase of the inner mitochondrial membrane permeability. The impact of a daily ration of food containing gold nanoparticles of two sizes (12 and

  18. Protective Effects of Salubrinal on Liver Injury in Rat Models of Brain Death

    Institute of Scientific and Technical Information of China (English)

    Tao Wang; Shui-Jun Zhang; Sheng-Li Cao; Wen-Zhi Guo; Bing Yan; Hong-Bo Fang

    2015-01-01

    Background:Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats.In this study,we observed the effect ofsalubrinal (Sal,Sigma,USA) on liver cells in BD rats and explored its relevant mechanisms.Methods:Thirty Sprague-Dawley rats were equally randomized into three groups:BD group,Sal group,and DMSO group.The BD models were established by increasing intracranial pressure in a modified,slow,and intermittent way.In the drug groups,Sal was administered l h before the induction of BD.After modeling was completed,the blood and liver samples were harvested.CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction.PKR-like ER kinase (PERK),P-eukaryotic translation initiation factor 2α (eIF2α),eIF2α,CHOP and caspase-12 expression was detected using western blotting (WB).CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC).Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer.Hepatic cell apoptosis was detected using TUNEL.The results were analyzed using Quantity-one v4.62 software (Bio-Rad,USA).Results:CHOP and caspase-12 expression and PERK,eIF2α,and P-eIF2α protein expression showed no significant difference between BD group and DMSO group.Compared with BD group,Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05).However,eIF2α expression showed no significant difference (P > 0.05).After the Sal treatment,CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05).WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment.Sal was associated with improved liver function and decreased hepatic cell apoptosis.Conclusions:Sal can significantly reduce apoptosis in hepatic cells of BD rats

  19. Brain-muscle-computer interface: mobile-phone prototype development and testing.

    Science.gov (United States)

    Vernon, Scott; Joshi, Sanjay S

    2011-07-01

    We report prototype development and testing of a new mobile-phone-based brain-muscle-computer interface for severely paralyzed persons, based on previous results from our group showing that humans may actively create specified power levels in two separate frequency bands of a single surface electromyography (sEMG) signal. EMG activity on the surface of a single face muscle site (auricularis superior) is recorded with a standard electrode. This analog electrical signal is imported into an Android-based mobile phone and digitized via an internal A/D converter. The digital signal is split, and then simultaneously filtered with two band-pass filters to extract total power within two separate frequency bands. The user-modulated power in each frequency band serves as two separate control channels for machine control. After signal processing, the Android phone sends commands to external devices via a Bluetooth interface. Users are trained to use the device via visually based operant conditioning, with simple cursor-to-target activities on the phone screen. The mobile-phone prototype interface is formally evaluated on a single advanced Spinal Muscle Atrophy subject, who has successfully used the interface in his home in evaluation trials and for remote control of a television. Development of this new device will not only guide future interface design for community use, but will also serve as an information technology bridge for in situ data collection to quantify human sEMG manipulation abilities for a relevant population.

  20. Brain Functional Connectivity is Different during VoluntaryConcentric and Eccentric Muscle Contraction

    Directory of Open Access Journals (Sweden)

    Wan X Yao

    2016-11-01

    Full Text Available Previous studies report greater activation in the cortical motor network in controlling eccentric contraction (EC than concentric contraction (CC of human skeletal muscles despite lower activation level of the muscle associated with EC. It is unknown, however, whether the strength of functional coupling between the primary motor cortex (M1 and other involved areas in the brain differs as voluntary movements are controlled by a network of regions in the primary, secondary and association cortices. Examining fMRI-based functional connectivity (FC offers an opportunity to measure strength of such coupling. To address the question, we examined functional MRI (fMRI data acquired during EC and CC (20 contractions each with similar movement distance and speed of the right first dorsal interosseous (FDI muscle in 11 young (20-32 years and healthy individuals and estimated FC between the M1 and a number of cortical regions in the motor control network. The major findings from the behavioral and fMRI-based FC analysis were that (1 no significant differences were seen in movement distance, speed and stability between the EC and CC; (2 significantly stronger mean FC was found for CC than EC. Our finding provides novel insights for a better understanding of the control mechanisms underlying voluntary movements produced by EC and CC. The finding is potentially helpful for guiding the development of targeted sport training and/or therapeutic programs for performance enhancement and injury prevention.

  1. A brain-machine-muscle interface for restoring hindlimb locomotion after complete spinal transection in rats.

    Directory of Open Access Journals (Sweden)

    Monzurul Alam

    Full Text Available A brain-machine interface (BMI is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics.

  2. Determination of trace elements in kidneys, livers and brains of rats with sealer implants by ICP-MS

    International Nuclear Information System (INIS)

    Simsek, Neslihan; Akinci, Levent; Alan, Hilal; Gecör, Orhan; Özan, Ülkü

    2017-01-01

    Following root canal treatment, sealers may contact periapical tissue. The purpose of this study was to evaluate the systemic toxic effects of epoxy resin-based sealers (AH Plus and Obtuseal). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure levels of trace elements (beryllium, magnesium, aluminium, calcium, chromium, arsenic and lead) in the brain, kidney and liver of rats. Twenty sterilized polyethylene tubes were then filled with AH Plus and Obtuseal and implanted into the dorsal subcutaneous tissue of 10 rats; three unoperated animals were used as a control group. After 45 days, the rats were sacrificed by cervical dislocation following anaesthesia, and brains, kidneys and livers were removed from all experimental animals. ICP-MS analysis was used to determine levels of trace elements. Data were analysed using Kruskal– Wallis and Connover post hoc tests. No significant differences were found in aluminium and calcium levels, but brains, kidneys and livers showed significantly higher amounts of magnesium and chromium than the corresponding controls. In the kidney and liver samples, arsenic levels were found to be higher than in the control group. Lead was detected at higher levels only in liver samples from the AH Plus group. Beryllium was not detected in any organ. It was concluded that AH Plus and Obtuseal release minimal quantities of trace elements when in contact with subcutaneous tissue, and further studies are needed to understand the systemic effects of these materials

  3. The acute effect of cannabis on plasma, liver and brain ammonia dynamics, a translational study.

    Science.gov (United States)

    Abulseoud, Osama A; Zuccoli, Maria Laura; Zhang, Lifeng; Barnes, Allan; Huestis, Marilyn A; Lin, Da-Ting

    2017-07-01

    Recent reports of ammonia released during cannabis smoking raise concerns about putative neurotoxic effects. Cannabis (54mg) was administered in a double-blind, placebo-controlled design to healthy cannabis users (n=15) either orally, or through smoking (6.9%THC cigarette) or inhalation of vaporized cannabis (Volcano®). Serial assay of plasma ammonia concentrations at 0, 2, 4, 6, 8, 10, 15, 30, and 90min from onset of cannabis administration showed significant time (P=0.016), and treatment (P=0.0004) effects with robust differences between placebo and edible at 30 (P=0.002), and 90min (P=0.007) and between placebo and vaporized (P=0.02) and smoking routes (P=0.01) at 90min. Furthermore, plasma ammonia positively correlated with blood THC concentrations (P=0.03). To test the hypothesis that this delayed increase in plasma ammonia originates from the brain we administered THC (3 and 10mg/kg) to mice and measured plasma, liver, and brain ammonia concentrations at 1, 3, 5 and 30min post-injection. Administration of THC to mice did not cause significant change in plasma ammonia concentrations within the first 5min, but significantly reduced striatal glutamine-synthetase (GS) activity (P=0.046) and increased striatal ammonia concentration (P=0.016). Furthermore, plasma THC correlated positively with striatal ammonia concentration (Pcannabis intake caused time and route-dependent increases in plasma ammonia concentrations in human cannabis users and reduced brain GS activity and increased brain and plasma ammonia concentrations in mice. Published by Elsevier B.V.

  4. In vivo formation of natural HgSe nanoparticles in the liver and brain of pilot whales

    DEFF Research Database (Denmark)

    Gajdosechova, Z.; Lawan, M. M.; Urgast, D. S.

    2016-01-01

    Se) nanoparticles in the liver and brain of long-finned pilot whales are attached to Se-rich structures and possibly act as a nucleation point for the formation of large Se-Hg clusters, which can grow with age to over 5 μm in size. The detoxification mechanism is fully developed from the early age of the animals...

  5. Noninvasive assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity

    Energy Technology Data Exchange (ETDEWEB)

    Klatt, Dieter [Department of Radiology, Charite-Universitaetsmedizin Berlin, Campus Charite Mitte, Chariteplatz 1, 10117 Berlin (Germany); Hamhaber, Uwe [Institute of Medical Informatics, Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin (Germany); Asbach, Patrick [Department of Radiology, Charite-Universitaetsmedizin Berlin, Campus Charite Mitte, Chariteplatz 1, 10117 Berlin (Germany); Braun, Juergen [Institute of Medical Informatics, Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin (Germany); Sack, Ingolf [Department of Radiology, Charite-Universitaetsmedizin Berlin, Campus Charite Mitte, Chariteplatz 1, 10117 Berlin (Germany)

    2007-12-21

    MR elastography (MRE) enables the noninvasive determination of the viscoelastic behavior of human internal organs based on their response to oscillatory shear stress. An experiment was developed that combines multifrequency shear wave actuation with broad-band motion sensitization to extend the dynamic range of a single MRE examination. With this strategy, multiple wave images corresponding to different driving frequencies are simultaneously received and can be analyzed by evaluating the dispersion of the complex modulus over frequency. The technique was applied on the brain and liver of five healthy volunteers. Its repeatability was tested by four follow-up studies in each volunteer. Five standard rheological models (Maxwell, Voigt, Zener, Jeffreys and fractional Zener model) were assessed for their ability to reproduce the observed dispersion curves. The three-parameter Zener model was found to yield the most consistent results with two shear moduli {mu}{sub 1} = 0.84 {+-} 0.22 (1.36 {+-} 0.31) kPa, {mu}{sub 2} = 2.03 {+-} 0.19 (1.86 {+-} 0.34) kPa and one shear viscosity of {eta} = 6.7 {+-} 1.3 (5.5 {+-} 1.6) Pa s (interindividual mean {+-} SD) in brain (liver) experiments. Significant differences between the rheological parameters of brain and liver were found for {mu}{sub 1} and {eta} (P < 0.05), indicating that human brain is softer and possesses a higher viscosity than liver.

  6. Noninvasive assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity

    International Nuclear Information System (INIS)

    Klatt, Dieter; Hamhaber, Uwe; Asbach, Patrick; Braun, Juergen; Sack, Ingolf

    2007-01-01

    MR elastography (MRE) enables the noninvasive determination of the viscoelastic behavior of human internal organs based on their response to oscillatory shear stress. An experiment was developed that combines multifrequency shear wave actuation with broad-band motion sensitization to extend the dynamic range of a single MRE examination. With this strategy, multiple wave images corresponding to different driving frequencies are simultaneously received and can be analyzed by evaluating the dispersion of the complex modulus over frequency. The technique was applied on the brain and liver of five healthy volunteers. Its repeatability was tested by four follow-up studies in each volunteer. Five standard rheological models (Maxwell, Voigt, Zener, Jeffreys and fractional Zener model) were assessed for their ability to reproduce the observed dispersion curves. The three-parameter Zener model was found to yield the most consistent results with two shear moduli μ 1 = 0.84 ± 0.22 (1.36 ± 0.31) kPa, μ 2 = 2.03 ± 0.19 (1.86 ± 0.34) kPa and one shear viscosity of η = 6.7 ± 1.3 (5.5 ± 1.6) Pa s (interindividual mean ± SD) in brain (liver) experiments. Significant differences between the rheological parameters of brain and liver were found for μ 1 and η (P < 0.05), indicating that human brain is softer and possesses a higher viscosity than liver

  7. Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro

    Directory of Open Access Journals (Sweden)

    Noemí de Luna

    2015-05-01

    Full Text Available McArdle disease, also termed ‘glycogen storage disease type V’, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM. It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL and brain (GP-BB isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA, a histone deacetylase inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with McArdle disease.

  8. Contribution of liver and skeletal muscle to alanine and lactate metabolism in humans

    International Nuclear Information System (INIS)

    Consoli, A.; Nurjhan, N.; Reilly, J.J. Jr.; Bier, D.M.; Gerich, J.E.

    1990-01-01

    To quantitate alanine and lactate gluconeogenesis in postabsorptive humans and to test the hypothesis that muscle is the principal source of these precursors, we infused normal volunteers with [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose and calculated alanine and lactate incorporation into plasma glucose corrected for tricarboxylic acid cycle carbon exchange, the systemic appearance of these substrates, and their forearm fractional extraction, uptake, and release. Forearm alanine and lactate fractional extraction averaged 37 +/- 3 and 27 +/- 2%, respectively; muscle alanine release (2.94 +/- 0.27 mumol.kg body wt-1.min-1) accounted for approximately 70% of its systemic appearance (4.18 +/- 0.31 mumol.kg body wt-1.min-1); muscle lactate release (5.51 +/- 0.42 mumol.kg body wt-1.min-1) accounted for approximately 40% of its systemic appearance (12.66 +/- 0.77 mumol.kg body wt-1.min-1); muscle alanine and lactate uptake (1.60 +/- 0.7 and 3.29 +/- 0.36 mumol.kg body wt-1.min-1, respectively) accounted for approximately 30% of their overall disappearance from plasma, whereas alanine and lactate incorporation into plasma glucose (1.83 +/- 0.20 and 4.24 +/- 0.44 mumol.kg body wt-1.min-1, respectively) accounted for approximately 50% of their disappearance from plasma. We therefore conclude that muscle is the major source of plasma alanine and lactate in postabsorptive humans and that factors regulating their release from muscle may thus exert an important influence on hepatic gluconeogenesis

  9. Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine

    DEFF Research Database (Denmark)

    Artmann, Andreas; Petersen, Gitte; Hellgren, Lars

    2008-01-01

    and docosahexaenoylethanolamide) with similar changes in precursor lipids. The AA-diet and FO-diet had no effect on N-acylethanolamines, endocannabinoids or precursor lipids in brain. All N-acylethanolamines activated PPAR-alpha. In conclusion, short-term feeding of diets resembling human diets (Mediterranean diet high...... (AA)) on tissue levels of 2-arachidonoylglycerol, anandamide, oleoylethanolamide, palmitoylethanolamide, stearoylethanolamide, linoleoylethanolamide, eicosapentaenoylethanolamide, docosahexaenoylethanolamide and tissue fatty acid composition. The LA-diet increased linoleoylethanolamide and linoleic...... acid in brain, jejunum and liver. The OA-diet increased brain levels of anandamide and oleoylethanolamide (not 2-arachidonoylglycerol) without changing tissue fatty acid composition. The same diet increased oleoylethanolamide in liver. All five dietary fats decreased oleoylethanolamide in jejunum...

  10. 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

    Science.gov (United States)

    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...

  11. Moderate nutrient restriction influences expression of genes impacting production efficiencies of beef cattle in fetal liver, muscle and cerebrum by day 50 of gestation

    Science.gov (United States)

    We hypothesized that a moderate maternal nutrient restriction during the first 50 days of gestation in beef heifers would affect expression of genes impacting production efficiency phenotypes in the fetal liver, muscle and cerebrum. Fourteen Angus-cross heifers were estrus synchronized and assigned ...

  12. Assessment of the antidiabetic potential of selected medicinal plants using in vitro bioassays of muscle glucose transport and liver glucose production

    DEFF Research Database (Denmark)

    Beidokhti, M N; Sanchez Villavicencio, M L; Eid, H M

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is the most common type of diabetes mellitus. It is caused by decreased insulin sensitivity in target organs like liver, muscle and adipose tissue, and/or a deficiency in insulin secretion. In T2DM, increased hepatic glucose output and decreased glucose uptake by s...

  13. (1)H-MRS measured ectopic fat in liver and muscle is associated with the metabolic syndrome in Danish girls but not in boys with overweight and obesity

    DEFF Research Database (Denmark)

    Nissen, A; Fonvig, Cilius E; Chabanova, E.

    2016-01-01

    BACKGROUND: The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between...

  14. Longitudinal intrinsic brain activity changes in cirrhotic patients before and one month after liver transplantation

    International Nuclear Information System (INIS)

    Cheng, Yue; Huang, Li Xiang; Xie, Shuang

    2017-01-01

    To evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI. Twenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis. In the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05). LT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time

  15. Longitudinal intrinsic brain activity changes in cirrhotic patients before and one month after liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yue; Huang, Li Xiang; Xie, Shuang [Dept. of Radiology, Tianjin First Central Hospital, Tianjin (China); and others

    2017-04-15

    To evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI. Twenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis. In the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05). LT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time.

  16. Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists.

    Science.gov (United States)

    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 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.

  17. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

    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. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    International Nuclear Information System (INIS)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-01-01

    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 [ 3 H]glucose and 2-deoxy[ 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

  19. Heterogeneous binding of sigma radioligands in the rat brain and liver

    International Nuclear Information System (INIS)

    Ross, S.B.

    1991-01-01

    The binding of four sigma receptor ligands, 3 H-(+)-N-allyl-N-normetazocine ( 3 H-(+)-SKF 10,047), 3 H-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ( 3 H-(+)-3-PPP), 3 H-haloperidol and 3 H-N,N'-di(o-totyl)guanidine ( 3 H-DTG), and the cytochrome P450IID6 ligand and dopamine uptake inhibitor 3 H-1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine ( 3 H-GBR 12935) to membranal preparations of rat liver or whole rat brain was examined regarding kinetical properties and inhibition by various compounds with affinity for sigma binding sites or cytochrome P-450. In rat brain the density of binding sites was increased in order (+)-SKF 10,047 3 H-(+)-SKF 10,047 there were quite marked differences between the ligands studied. Multiple binding sites were also indicated by the low Hill coefficients found for most of the compounds studied. It was found that the cytochrome P-450 inhibitor proadifen (SKF 525A), like haloperidol, was a potent inhibitor of the binding of 3 H-(+)-SKF 10,047, 3 H-(+)-3-PPP and 3 H-haloperidol to the liver and brain preparations, less active in inhibiting the binding of 3 H-DTG and least effective on the binding of 3 H-GBR 12935. Another cytochrome P-450 inhibitor, L-lobeline, was particularly potent in inhibiting the binding of 3 H-DTG but was also quite potent inhibitor of the binding of the other sigma ligands. It was less potent in inhibiting the binding of 3 H-GBR 12935. The binding of the latter ligand was potently inhibited by the analogous compound GBR 12909 but of the other compounds examined only L-lobeline, proadifen, haloperidol, DTG and (+)-3-PPP had IC50 values below 10 μM. The possibility that the sigma binding sites are identical with some subforms of cytochrome P-450 is discussed. (author)

  20. Mercury in human brain, blood, muscle and toenails in relation to exposure: an autopsy study

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    Morild Inge

    2007-10-01

    Full Text Available Abstract Background The main forms of mercury (Hg exposure in the general population are methylmercury (MeHg from seafood, inorganic mercury (I-Hg from food, and mercury vapor (Hg0 from dental amalgam restorations. While the distribution of MeHg in the body is described by a one compartment model, the distribution of I-Hg after exposure to elemental mercury is more complex, and there is no biomarker for I-Hg in the brain. The aim of this study was to elucidate the relationships between on the one hand MeHg and I-Hg in human brain and other tissues, including blood, and on the other Hg exposure via dental amalgam in a fish-eating population. In addition, the use of blood and toenails as biological indicator media for inorganic and organic mercury (MeHg in the tissues was evaluated. Methods Samples of blood, brain (occipital lobe cortex, pituitary, thyroid, abdominal muscle and toenails were collected at autopsy of 30 deceased individuals, age from 47 to 91 years of age. Concentrations of total-Hg and I-Hg in blood and brain cortex were determined by cold vapor atomic fluorescence spectrometry and total-Hg in other tissues by sector field inductively coupled plasma-mass spectrometry (ICP-SFMS. Results The median concentrations of MeHg (total-Hg minus I-Hg and I-Hg in blood were 2.2 and 1.0 μg/L, and in occipital lobe cortex 4 and 5 μg/kg, respectively. There was a significant correlation between MeHg in blood and occipital cortex. Also, total-Hg in toenails correlated with MeHg in both blood and occipital lobe. I-Hg in both blood and occipital cortex, as well as total-Hg in pituitary and thyroid were strongly associated with the number of dental amalgam surfaces at the time of death. Conclusion In a fish-eating population, intake of MeHg via the diet has a marked impact on the MeHg concentration in the brain, while exposure to dental amalgam restorations increases the I-Hg concentrations in the brain. Discrimination between mercury species is

  1. Effects of Eleutherococcus senticosus Cortex on Recovery from the Forced Swimming Test and Fatty Acid β-Oxidation in the Liver and Skeletal Muscle of mice.

    Science.gov (United States)

    Sumiyoshi, Maho; Kimura, Yoshiyuki

    2016-03-01

    The root and stem barks of Eleutherococcus senticosus have been used to treat emotional and physical fatigue in China, Russia, Korea, and Japan. The effects of E. senticosus on recovery from physical fatigue and the expenditure of energy currently remain unclear. We herein examined the effects of E. senticosus extract on recovery from physical fatigue after the forced swimming test as well as fatty acid β-oxidation in the liver and skeletal muscle of mice. 1) Physical fatigue; E. senticosus extract (500 and 1000 mg/kg, twice daily) was administered orally to ICR male mice for 7 consecutive days. After swimming had been performed for 15 min, each mouse was placed on the cover of a 100-mm culture plate, and the time for each mouse to move away from the cover was measured. 2) Fatty acid β-oxidation in the liver and skeletal muscle; E. senticosus extract (500 and 1000 mg/kg) was administered orally twice daily to C57BL/6J male mice for 21 consecutive days. The initial and final body and liver weight were measured, and then fatty acid β-oxidation activity in the liver and skeletal muscle was measured by methods using [1- 14 C] palmitic acid. Recovery times after forced swimming were shorter in E. senticosus extract (500 and 1000 mg/kg)-treated mice than in vehicle-treated mice. The body and liver weight had no effect by the oral administration of E. senticosus extract, vitamin mixture and L-carnitine. Fatty acid β-oxidation activity in skeletal muscle was increased by E. senticosus extract (500 and 1000 mg/kg). E. senticosus may enhance recovery from physical fatigue induced by forced swimming by accelerating energy changes through fatty acid β-oxidation in skeletal muscle.

  2. Heavy metal levels in the liver and muscle tissues of the four commercial fishes from Lake Balik, Kızılırmak Delta (Samsun, Turkey

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    Levent Bat

    2015-12-01

    Full Text Available Objective: To determine the levels of some heavy metals in the liver and edible tissues of four fish species [Mugil cephalus L., 1758 (M. cephalus, Cyprinus carpio L., 1758 (C. carpio, Perca fluviatilis L., 1758 (P. fluviatilis and Stizostedion lucioperca L., 1758 (S. lucioperca] collected from Lake Balik, Kizilirmak Delta (Samsun for analysis of Cu, Co, Pb, Zn, Cd, Mn, Ni and Fe. These metals were chosen because at higher concentrations there might be toxic to the fish and by extension humans that depends on such fish as food. Methods: The concentrations of the metals were carried out by the flame atomic absorption spectrophotometer (UNICAM 929. Results: Large differences in heavy metal levels were observed between liver and muscle tissues within each fish. The results showed that the Fe concentrations were the highest and Cd concentrations were the lowest in livers and edible tissues of the four species. The muscles of C. carpio accumulated significant higher levels of Co, Zn and Ni than other species. Cu was higher in the muscles of S. lucioperca than those in other species, while M. cephalus showed more of Mn and Fe levels. The muscles of P. fluviatilis accumulated significant higher levels of Pb and Cd than other species. However, the liver of M. cephalus accumulated significant higher levels of Co, Mn and Fe than other species. The level of Cd was the highest in the liver of P. fluviatilis, while S. lucioperca showed more of Cu and Pb, and the higher levels of Zn and Ni was measured in the liver of C. carpio. Conclusions: The metal levels obtained were compared with the maximum permitted levels in food of the Turkish Food Codex and Commission Regulation (EC. The results of this study showed that estimated daily and weekly intakes of selected metals via consumption of fish were below the permissible tolerable daily intake and provisional tolerable weekly intake values established by Food and Agriculture Organization/World Health

  3. Age-related fat deposition in multifidus muscle could be a marker for nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Kitajima, Yoichiro; Eguchi, Yuichiro; Ishibashi, Eriko

    2010-01-01

    Although nonalcoholic fatty liver disease (NAFLD) is associated with visceral obesity, the relationship between visceral fat accumulation and skeletal muscle steatosis in patients with NAFLD has not been established. We evaluated: the relationship between multifidus muscular tissue steatosis, visceral fat accumulation, and biochemical data in a cross-sectional study, and the influence of weight reduction on multifidus muscular tissue steatosis in a longitudinal study. Three hundred thirty-three NAFLD patients were enrolled. Hepatic steatosis, visceral fat area, and the multifidus muscle/subcutaneous fat attenuation ratio (MM/F ratio) were evaluated by computed tomography. To evaluate how weight reduction produced by diet and exercise affected the MM/F ratio, changes in the MM/F ratio were compared between weight reduction and non-weight reduction groups. There was a gender difference in MM/F ratios. The MM/F ratio was significantly correlated with age (male r=0.613, P<0.01; female r=0.440, P<0.01). The MM/F ratio was positively correlated with visceral fat area (male: r=0.262, P<0.01; female: r=0.214, P<0.01). A decrease in the MM/F ratio, concomitant with reduced visceral fat accumulation, led to alleviation of hepatic steatosis in 20 patients with weight reduction, but not in 22 patients without weight reduction. The MM/F ratio was closely related to aging and visceral fat accumulation. The MM/F ratio was improved by weight reduction, indicating that fat accumulation in the multifidus muscle evaluated by computed tomography might be a therapeutic indicator of NAFLD. (author)

  4. One-year high fat diet affects muscle-but not brain mitochondria

    DEFF Research Database (Denmark)

    Joergensen, Tenna; Grunnet, Niels; Quistorff, Bjørn

    2015-01-01

    It is well known that few weeks of high fat (HF) diet may induce metabolic disturbances and mitochondrial dysfunction in skeletalmuscle. However, little is known about the effects of long-term HF exposure and effects on brain mitochondria are unknown. Wistarrats were fed either chow (13E% fat......) or HF diet (60E% fat) for 1 year. The HF animals developed obesity, dyslipidemia, insulinresistance, and dysfunction of isolated skeletal muscle mitochondria: state 3 and state 4 were 30% to 50% increased (P .... Adding also succinate in state 3 resulted in ahigher substrate control ratio (SCR) with PC, but a lower SCR with pyruvate (P mitochondria from the same animal showed no changes with the substrates relevant...

  5. Muscle and Liver Carbohydrates: Response to Military Task Performance by Women and Men

    Science.gov (United States)

    2001-10-01

    three different occasions with the knee at three different degrees of flexion / extension. Knee orientations were: 1) plantar flexion with the knee fully...extended (1800), 2) plantar flexion with the knee flexed at 900, and 3) plantar flexion with the knee at an intermediate extension (135’). This data...selected so as to avoid vessels, fascia , and MRI artifacts. In order to accumulate a statistically significant number of ROI’s for each muscle in a given

  6. Brain cytoplasmic RNA 1 suppresses smooth muscle differentiation and vascular development in mice.

    Science.gov (United States)

    Wang, Yung-Chun; Chuang, Ya-Hui; Shao, Qiang; Chen, Jian-Fu; Chen, Shi-You

    2018-04-13

    The cardiovascular system develops during the early stages of embryogenesis, and differentiation of smooth muscle cells (SMCs) is essential for that process. SMC differentiation is critically regulated by transforming growth factor (TGF)-β/SMAD family member 3 (SMAD3) signaling, but other regulators may also play a role. For example, long noncoding RNAs (lncRNAs) regulate various cellular activities and events, such as proliferation, differentiation, and apoptosis. However, whether long noncoding RNAs also regulate SMC differentiation remains largely unknown. Here, using the murine cell line C3H10T1/2, we found that brain cytoplasmic RNA 1 (BC1) is an important regulator of SMC differentiation. BC1 overexpression suppressed, whereas BC1 knockdown promoted, TGF-β-induced SMC differentiation, as indicated by altered cell morphology and expression of multiple SMC markers, including smooth muscle α-actin (αSMA), calponin, and smooth muscle 22α (SM22α). BC1 appeared to block SMAD3 activity and inhibit SMC marker gene transcription. Mechanistically, BC1 bound to SMAD3 via RNA SMAD-binding elements (rSBEs) and thus impeded TGF-β-induced SMAD3 translocation to the nucleus. This prevented SMAD3 from binding to SBEs in SMC marker gene promoters, an essential event in SMC marker transcription. In vivo , BC1 overexpression in mouse embryos impaired vascular SMC differentiation, leading to structural defects in the artery wall, such as random breaks in the elastic lamina, abnormal collagen deposition on SM fibers, and disorganized extracellular matrix proteins in the media of the neonatal aorta. Our results suggest that BC1 is a suppressor of SMC differentiation during vascular development. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Successful Treatment of Combined Aspergillus and Cytomegalovirus Abscess in Brain and Lung After Liver Transplant for Toxic Fulminant Hepatitis.

    Science.gov (United States)

    Kim, Tae-Seok; Ahn, Keun Soo; Kim, Yong Hoon; Kim, Hyoung Tae; Jang, Byoung Kuk; Hwang, Jae Seok; Kim, Il-Man; Kang, Yu Na; Kang, Koo Jeong

    2017-02-01

    Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels.

  8. Ames dwarf (Prop1(df)/Prop1(df)) mice display increased sensitivity of the major GH-signaling pathways in liver and skeletal muscle.

    Science.gov (United States)

    Miquet, Johanna G; Muñoz, Marina C; Giani, Jorge F; González, Lorena; Dominici, Fernando P; Bartke, Andrzej; Turyn, Daniel; Sotelo, Ana I

    2010-04-01

    Growth hormone (GH) is an anabolic hormone that regulates growth and metabolism. Ames dwarf mice are natural mutants for Prop1, with impaired development of anterior pituitary and undetectable levels of circulating GH, prolactin and TSH. They constitute an endocrine model of life-long GH-deficiency. The main signaling cascades activated by GH binding to its receptor are the JAK2/STATs, PI-3K/Akt and the MAPK Erk1/2 pathways. We have previously reported that GH-induced STAT5 activation was higher in Ames dwarf mice liver compared to non-dwarf controls. The aim of this study was to evaluate the principal components of the main GH-signaling pathways under GH-deficiency in liver and skeletal muscle, another GH-target tissue. Ames dwarf mice and their non-dwarf siblings were assessed. Animals were injected i.p. with GH or saline 15min before tissue removal. Protein content and phosphorylation of signaling mediators were determined by immunoblotting of tissue solubilizates. GH was able to induce STAT5 and STAT3 tyrosine phosphorylation in both liver and muscle, but the response was higher for Ames dwarf mice than for non-dwarf controls. When Erk1/2 activation was assessed in liver, only dwarf mice showed GH-induced phosphorylation, while in muscle no response to the hormone was found in either genotype. GH-induced Akt phosphorylation at Ser473 in liver was only detected in dwarf mice. In skeletal muscle, both normal and dwarf mice responded to a GH stimulus, although dwarf mice presented higher GH activation levels. The phosphorylation of GSK-3, a substrate of Akt, increased upon hormone stimulation only in dwarf mice in both tissues. In contrast, no differences in the phosphorylation of mTOR, another substrate of Akt, were observed after GH stimulus, either in normal or dwarf mice in liver, while we were unable to determine mTOR in muscle. Protein content of GH-receptor and of the signaling mediators studied did not vary between normal and dwarf animals in the assessed

  9. Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney.

    Science.gov (United States)

    Ebrahimkhani, Mohammad R; Daneshmand, Ali; Mazumder, Aprotim; Allocca, Mariacarmela; Calvo, Jennifer A; Abolhassani, Nona; Jhun, Iny; Muthupalani, Sureshkumar; Ayata, Cenk; Samson, Leona D

    2014-11-11

    Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by the inflammation-associated RONS release that accompanies ischemia reperfusion (I/R). Using mouse I/R models we demonstrate that Aag(-/-) mice are significantly protected against, rather than sensitized to, I/R injury, and that such protection is observed across three different organs. Following I/R in liver, kidney, and brain, Aag(-/-) mice display decreased hepatocyte death, cerebral infarction, and renal injury relative to wild-type. We infer that in wild-type mice, Aag excises damaged DNA bases to generate potentially toxic abasic sites that in turn generate highly toxic DNA strand breaks that trigger poly(ADP-ribose) polymerase (Parp) hyperactivation, cellular bioenergetics failure, and necrosis; indeed, steady-state levels of abasic sites and nuclear PAR polymers were significantly more elevated in wild-type vs. Aag(-/-) liver after I/R. This increase in PAR polymers was accompanied by depletion of intracellular NAD and ATP levels plus the translocation and extracellular release of the high-mobility group box 1 (Hmgb1) nuclear protein, activating the sterile inflammatory response. We thus demonstrate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a novel target for controlling I/R-induced injury.

  10. The total body mass of fatty acid ethyl esters in skeletal muscles following ethanol exposure greatly exceeds that found in the liver and the heart.

    Science.gov (United States)

    Salem, Raneem O; Laposata, Michael; Rajendram, Rajkumar; Cluette-Brown, Joanne E; Preedy, Victor R

    2006-01-01

    Skeletal muscle appears to be susceptible to chronic and acute excess alcohol intake, giving rise to alcoholic myopathy, a common disease among alcoholics. Fatty acid ethyl esters (FAEE), non-oxidative metabolites of ethanol, have been shown to be toxic to cells in vitro and in vivo. We hypothesized that accumulation of FAEE in skeletal muscle could contribute to the development of alcoholic myopathy. Male wistar rats were treated either with 75 mmol ethanol/kg body weight or saline, in the fed state or starved for 1 or 2 days before administration. Rats were thus divided into the following groups: fed-saline (n = 8); fed-ethanol (n = 8); starved 1 day, saline (n = 8); starved 1 day, ethanol (n = 9); starved 2 days, saline (n = 7); and starved 2 days, ethanol (n = 8). At the end of the incubation, skeletal muscles (abdominal and gastrocnemius), liver, and heart were isolated and processed for FAEE isolation and analysis by gas chromatography-mass spectrometry (GC-MS). Total mass of FAEE in the muscles was much greater than that found in the liver and the heart. In general, the animals that were fasted for 1 day and received ethanol had the highest FAEE levels among the three groups of animals. The major ethyl ester species in all cases were ethyl 16:0, ethyl 18:0, ethyl 18:1 n-9, and ethyl 18:2 n-6. Ethyl 20:4 n-6 and ethyl 22:6 n-3 were also present, except in the fasted 1-day group, where ethyl 22:6 disappeared, though it reappeared in the fasted 2-day group. These findings demonstrate that skeletal muscles contain high levels of FAEE that are synthesized in the body after ethanol exposure. The concentration of FAEE in skeletal muscle in this study was very similar to FAEE concentration in the liver. This differs from previous studies suggesting a low concentration of skeletal muscle FAEE with ethanol exposure.

  11. Effect of methyl parathion on the muscle and brain acetylcholinesterase activity of matrinxã (Brycon cephalus

    Directory of Open Access Journals (Sweden)

    Almeida Luciana Cristina de

    2005-01-01

    Full Text Available Farming of the freshwater fish is emerging in Brazil and many species from the wild are promising. The teleost matrinxã (Brycon cephalus holds several characteristics such as fast growth rate, high commercial value and adaptability to artificial raring conditions, which make it a promising species for commerce. The use of pesticides in aquatic environment is frequent in Brazil, and methyl parathion is very common in aquaculture. We have determined the enzymatic activity of acetyl cholinesterase in white muscle and brain of matrinxã exposed to 2ppm of environmental methyl parathion for 24 hours. There was 64% and 69% of acetyl cholinesterase inhibition in muscle and brain respectively. These activities were not recovered after 8 days from exposure to this pesticide. It can be concluded that acetyl cholinesterase from those tissues was inhibited by small amounts of methyl parathion, and the main effect was observed in the brain.

  12. CT and MRI assessment and characterization using segmentation and 3D modeling techniques: applications to muscle, bone and brain

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    Paolo Gargiulo

    2014-03-01

    Full Text Available This paper reviews the novel use of CT and MRI data and image processing tools to segment and reconstruct tissue images in 3D to determine characteristics of muscle, bone and brain.This to study and simulate the structural changes occurring in healthy and pathological conditions as well as in response to clinical treatments. Here we report the application of this methodology to evaluate and quantify: 1. progression of atrophy in human muscle subsequent to permanent lower motor neuron (LMN denervation, 2. muscle recovery as induced by functional electrical stimulation (FES, 3. bone quality in patients undergoing total hip replacement and 4. to model the electrical activity of the brain. Study 1: CT data and segmentation techniques were used to quantify changes in muscle density and composition by associating the Hounsfield unit values of muscle, adipose and fibrous connective tissue with different colors. This method was employed to monitor patients who have permanent muscle LMN denervation in the lower extremities under two different conditions: permanent LMN denervated not electrically stimulated and stimulated. Study 2: CT data and segmentation techniques were employed, however, in this work we assessed bone and muscle conditions in the pre-operative CT scans of patients scheduled to undergo total hip replacement. In this work, the overall anatomical structure, the bone mineral density (BMD and compactness of quadriceps muscles and proximal femoral was computed to provide a more complete view for surgeons when deciding which implant technology to use. Further, a Finite element analysis provided a map of the strains around the proximal femur socket when solicited by typical stresses caused by an implant press fitting. Study 3 describes a method to model the electrical behavior of human brain using segmented MR images. The aim of the work is to use these models to predict the electrical activity of the human brain under normal and pathological

  13. Assessing Brain–Muscle Connectivity in Human Locomotion through Mobile Brain/Body Imaging: Opportunities, Pitfalls, and Future Directions

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    Federico Gennaro

    2018-02-01

    Full Text Available Assessment of the cortical role during bipedalism has been a methodological challenge. While surface electroencephalography (EEG is capable of non-invasively measuring cortical activity during human locomotion, it is associated with movement artifacts obscuring cerebral sources of activity. Recently, statistical methods based on blind source separation revealed potential for resolving this issue, by segregating non-cerebral/artifactual from cerebral sources of activity. This step marked a new opportunity for the investigation of the brains’ role while moving and was tagged mobile brain/body imaging (MoBI. This methodology involves simultaneous mobile recording of brain activity with several other body behavioral variables (e.g., muscle activity and kinematics, through wireless recording wearable devices/sensors. Notably, several MoBI studies using EEG–EMG approaches recently showed that the brain is functionally connected to the muscles and active throughout the whole gait cycle and, thus, rejecting the long-lasting idea of a solely spinal-driven bipedalism. However, MoBI and brain/muscle connectivity assessments during human locomotion are still in their fledgling state of investigation. Mobile brain/body imaging approaches hint toward promising opportunities; however, there are some remaining pitfalls that need to be resolved before considering their routine clinical use. This article discusses several of these pitfalls and proposes research to address them. Examples relate to the validity, reliability, and reproducibility of this method in ecologically valid scenarios and in different populations. Furthermore, whether brain/muscle connectivity within the MoBI framework represents a potential biomarker in neuromuscular syndromes where gait disturbances are evident (e.g., age-related sarcopenia remains to be determined.

  14. Exercise-Induced Changes in Caveolin-1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver

    Directory of Open Access Journals (Sweden)

    Damian Jozef Flis

    2016-01-01

    Full Text Available The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1 plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise.

  15. Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

    Science.gov (United States)

    Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

    2006-01-01

    CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

  16. Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E

    2007-01-01

    Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... incision repair (P = 0.014) were all increased, while protein oxidation decreased (P = 0.003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may...

  17. Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.

    Directory of Open Access Journals (Sweden)

    Elizabeth Osterndorff-Kahanek

    Full Text Available Chronically available alcohol escalates drinking in mice and a single injection of the immune activator lipopolysaccharide can mimic this effect and result in a persistent increase in alcohol consumption. We hypothesized that chronic alcohol drinking and lipopolysaccharide injections will produce some similar molecular changes that play a role in regulation of alcohol intake. We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes among four groups of animals, three consuming alcohol (vs water in different consumption tests and one injected with lipopolysaccharide (vs. vehicle. The three tests of alcohol consumption are the continuous chronic two bottle choice (Chronic, two bottle choice available every other day (Chronic Intermittent and limited access to one bottle of ethanol (Drinking in the Dark. Gene expression changes were more numerous and marked in liver than in prefrontal cortex for the alcohol treatments and similar in the two tissues for lipopolysaccharide. Many of the changes were unique to each treatment, but there was significant overlap in prefrontal cortex for Chronic-Chronic Intermittent and for Chronic Intermittent-lipopolysaccharide and in liver all pairs showed overlap. In silico cell-type analysis indicated that lipopolysaccharide had strongest effects on brain microglia and liver Kupffer cells. Pathway analysis detected a prefrontal cortex-based dopamine-related (PPP1R1B, DRD1, DRD2, FOSB, PDNY network that was highly over-represented in the Chronic Intermittent group, with several genes from the network being also regulated in the Chronic and lipopolysaccharide (but not Drinking in the Dark groups. Liver showed a CYP and GST centered metabolic network shared in part by all four treatments. We demonstrate common consequences of chronic alcohol

  18. Mitochondrial energetic metabolism perturbations in skeletal muscles and brain of zebrafish (Danio rerio) exposed to low concentrations of waterborne uranium

    Energy Technology Data Exchange (ETDEWEB)

    Lerebours, Adelaide; Adam-Guillermin, Christelle [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Bat 186, BP 3, 13115 Saint-Paul-Lez-Durance Cedex (France); Brethes, Daniel [CNRS, UMR 5095, Institut de Biochimie et Genetique Cellulaires, Universite Victor Segalen-Bordeaux 2 (France); Frelon, Sandrine; Floriani, Magali; Camilleri, Virginie; Garnier-Laplace, Jacqueline [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Bat 186, BP 3, 13115 Saint-Paul-Lez-Durance Cedex (France); Bourdineaud, Jean-Paul, E-mail: jp.bourdineaud@epoc.u-bordeaux1.fr [CNRS, UMR 5095, Institut de Biochimie et Genetique Cellulaires, Universite Victor Segalen-Bordeaux 2 (France)

    2010-10-01

    Anthropogenic release of uranium (U), originating from the nuclear fuel cycle or military activities, may considerably increase U concentrations in terrestrial and aquatic ecosystems above the naturally occurring background levels found throughout the environment. With a projected increase in the world-wide use of nuclear power, it is important to improve our understanding of the possible effects of this metal on the aquatic fauna at concentrations commensurate with the provisional drinking water guideline value of the World Health Organization (15 {mu}g U/L). The present study has examined the mitochondrial function in brain and skeletal muscles of the zebrafish, Danio rerio, exposed to 30 and 100 {mu}g/L of waterborne U for 10 and 28 days. At the lower concentration, the basal mitochondrial respiration rate was increased in brain at day 10 and in muscles at day 28. This is due to an increase of the inner mitochondrial membrane permeability, resulting in a decrease of the respiratory control ratio. In addition, levels of cytochrome c oxidase subunit IV (COX-IV) increased in brain at day 10, and those of COX-I increased in muscles at day 28. Histological analyses performed by transmission electron microscopy revealed an alteration of myofibrils and a dilatation of endomysium in muscle cells. These effects were largest at the lowest concentration, following 28 days of exposure.

  19. Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Osama H. Elshenawy

    2017-02-01

    Full Text Available Cytochrome P450-mediated metabolism of arachidonic acid (AA is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal 19 ischemia/reperfusion (I/R injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future.

  20. Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz; Farkhondeh, Tahereh

    2016-04-01

    Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

  1. Effects of adrenal hormones on the expression of adiponectin and adiponectin receptors in adipose tissue, muscle and liver.

    Science.gov (United States)

    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.

  2. 1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents

    DEFF Research Database (Denmark)

    Fonvig, Cilius Esmann; Chabanova, Elizaveta; Andersson, Ehm Astrid

    2015-01-01

    .2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat...... associated inversely to high density lipoprotein cholesterol. CONCLUSION: Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased...

  3. Acute Effects of Moderate and Strenuous Running on Trace Element Distribution in the Brain, Liver, and Spleen of Trained Rats

    Directory of Open Access Journals (Sweden)

    Kıvanç Ergen

    2013-03-01

    Full Text Available Objective: Trace elements such as manganese (Mn, cobalt (Co and chromium (Cr play key roles in metabolic reactions and are important in many physiological enzymatic processes. In this study, we aimed to investigate the acute effects of moderate and strenuous running (treadmill exercise on the levels of Mn, Co and Cr in the brain, liver, and spleen of trained rats. Study Design: Animal experiment. Material and Methods: Twenty-one Wistar-Albino adult male rats were used in the study. Rats were grouped as control group (no mandated exercise; n=8, moderate exercise group (30 min exercise duration; n=7, and strenuous exercise group (60 min exercise duration; n=6. The levels of Mn, Co, and Cr in the frontal lobe, temporal lobe, brain stem, liver, and spleen were determined by atomic absorption spectrophotometer. Results: Cr levels in liver of rats increased in parallel to the time course of running supporting the exercise training effect on the action of insulin. Compared to the control group, the level of Co significantly decreased in the brain stem of rats in the moderate exercise group (p=0.009 and in the frontal lobe of rats in the strenuous exercise group (p=0.004. In the strenuous exercise group, an examination of the brain stem revealed that the level of Mn significantly decreased (p=0.001, and levels of Co and Cr were apparently depleted to the extent that these elements were no longer detectable. Conclusion: A notable finding is that during or after single bout strenuous exercise, levels of Co decreased in the spleen and particularly decreased in the brain stem of regularly trained rats. From this study, it can be inferred that sportsmen should aware trace element disturbances among the body parts or depletion of some trace elements after single bout of chronic strenuous running exercise.

  4. Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

    Directory of Open Access Journals (Sweden)

    Keith M Godfrey

    Full Text Available Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001 and at age 4 years (r = 0.16, P = 0.02. In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02. This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04. We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

  5. The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters

    DEFF Research Database (Denmark)

    Nielsen, Mette J; Nedergaard, Anders F; Sun, Shu

    2013-01-01

    AIM: The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3). METHODS: The monoclonal antibody...... was raised against the N-protease mediated cleavage site of the N-terminal propeptide of type III collagen and a competitive ELISA was developed using the selected antibody. The assay was evaluated in relation to neo-epitope specificity, technical performance, and as a marker for liver fibrosis and muscle...... mass using the rat carbon tetrachloride (CCl4) model and a study of immobilization induced muscle loss in humans, respectively. RESULTS: The ELISA was neo-epitope specific, technically stable and can be assessed in serum and plasma samples. In the CCl4 liver fibrosis model it was observed that serum...

  6. Clinical Outcomes of Living Liver Transplantation According to the Presence of Sarcopenia as Defined by Skeletal Muscle Mass, Hand Grip, and Gait Speed.

    Science.gov (United States)

    Harimoto, N; Yoshizumi, T; Izumi, T; Motomura, T; Harada, N; Itoh, S; Ikegami, T; Uchiyama, H; Soejima, Y; Nishie, A; Kamishima, T; Kusaba, R; Shirabe, K; Maehara, Y

    2017-11-01

    Sarcopenia is an independent predictor of death after living-donor liver transplantation (LDLT). However, the ability of the Asian Working Group for Sarcopenia criteria for sarcopenia (defined as reduced skeletal muscle mass plus low muscle strength) to predict surgical outcomes in patients who have undergone LDLT has not been determined. This study prospectively enrolled 366 patients who underwent LDLT at Kyushu University Hospital. Skeletal muscle area (determined by computed tomography), hand-grip strength, and gait speed were measured in 102 patients before LDLT. We investigated the relationship between sarcopenia and surgical outcomes after LDLT performed in three time periods. The number of patients with lower skeletal muscle area has increased to 52.9% in recent years. The incidence of sarcopenia according to the Asian Working Group for Sarcopenia criteria was 23.5% (24/102). Patients with sarcopenia (defined by skeletal muscle area and functional parameters) had significantly lower skeletal muscle area and weaker hand-grip strength than did those without sarcopenia. Compared with non-sarcopenic patients, patients with sarcopenia also had significantly worse liver function, greater estimated blood loss, greater incidence of postoperative complications of Clavien-Dindo grade IV or greater (including amount of ascites on postoperative day 14, total bilirubin on postoperative day 14, and postoperative sepsis), and longer postoperative hospital stay. Multiple logistic regression analysis revealed sarcopenia as a significant predictor of 6-month mortality. The combination of skeletal muscle mass and function can predict surgical outcomes in LDLT patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effect of γ-ray Irradiation On the Activities of Monoamine Oxidase in Rat Brain and Liver

    International Nuclear Information System (INIS)

    Kim, Joo Young; Choi, Myung Sun; Choi, Myung Un

    1993-01-01

    In order to evaluate the effects of radiation on mammalian neuronal system, we have examined the effect of gamma-ray radiation on the monoamine oxidase(MAO) activity in monoaminergic neurons. Following the whole body irradiation, MAO activity in the rat brain was measured as well as in the liver for the comparative studies between the neuronal and nonneuronal system. The effects of some radiation protectors and sensitizers were also examined in addition to the O2 effect. The results can be summarized as follows. 1) The MAO activity of rat brain was minimally affected by the radiation dose up to 1,700 cGy. Radiation dose above 2,500 cGy inhibited the brain MAO activity by no less than 10%. MAO-A form was found to be particularly sensitive to radiation. The liver MAO was somewhat inhibited(by about 5%) but hard1y dependent on the dose of radiation. 2) The inhibitory effect on the brain was initiated immediately by the radiation dose of 2,500 cGy. On the contrary, for the liver, the inhibitory effect became apparent only 2 days after irradiation. 3) Two days after a dose of 2,500 cGy, Vmax and Km of the brain mitochondrial MAO decreased. for liver, Vmax decreased while Km increased, which indicates the kinetic patterns for the neuronal and nonneruronal systems are not affected similarly by radiation. 4) The effect of several known radiation protectors and sensitizers on MAO activity was tested but no definite results were obtained. The level of -SH group increased in some degree upon radiation but not by the compounds. 5) MAO activity was not affected by O2 concentration, while an elevated level of lipid peroxidase was found udder the same condition. The results described here indicate that characteristics of MAO, one of the most important central nervous system enzymes, are liable to radiation, which is partially differentiated from the liver MAO. Also indicated are that the -SH groups are hardly related to the effect of radiation but the production of the lipid

  8. The insulin receptor substrate 1 associates with phosphotyrosine phosphatase SHPTP2 in liver and muscle of rats

    Directory of Open Access Journals (Sweden)

    Lima M.H.M.

    1998-01-01

    Full Text Available Insulin stimulates the tyrosine kinase activity of its receptor resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1 which, in turn, associates with proteins containing SH2 domains. It has been shown that IRS-1 associates with the tyrosine phosphatase SHPTP2 in cell cultures. While the effect of the IRS-1/SHPTP2 association on insulin signal transduction is not completely known, this association may dephosphorylate IRS-1 and may play a critical role in the mitogenic actions of insulin. However, there is no physiological demonstration of this pathway of insulin action in animal tissues. In the present study we investigated the ability of insulin to induce association between IRS-1 and SHPTP2 in liver and muscle of intact rats, by co-immunoprecipitation with anti-IRS-1 antibody and anti-SHPTP2 antibody. In both tissues there was an increase in IRS-1 association with SHPTP2 after insulin stimulation. This association occurred when IRS-1 had the highest level of tyrosine phosphorylation and the decrease in this association was more rapid than the decrease in IRS-1 phosphorylation levels. The data provide evidence against the participation of SHPTP2 in IRS-1 dephosphorylation in rat tissues, and suggest that the insulin signal transduction pathway in rat tissues is related mainly to the mitogenic effects of the hormone.

  9. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain?liver axis

    OpenAIRE

    Yang, B; Ren, Q; Zhang, J-c; Chen, Q-X; Hashimoto, K

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF...

  10. Preparation of bovine muscle, bovine liver and pig kidney reference materials and the certification of the contents of nine elements of toxicological and nutritional interest

    International Nuclear Information System (INIS)

    Wagstaffe, P.J.; Muntau, H.

    1987-01-01

    The preparation of 3 meat reference materials (bovine muscle, bovine liver and pig kidney) and the steps taken to confirm their homogeneity and stability are described. Details are presented of a preliminary intercomparison and of the final collaborative exercise which led to the certification of the contents of 9 elements of toxicological and nutritional importance. Indicative values are given for the contents of a further 9 elements in these materials. (orig.)

  11. The Teratogenicity and the Action Mechanism of Gallic Acid Relating with Brain and Cervical Muscles

    Science.gov (United States)

    Hsieh, Chiu Lan; Lin, Chien-Hong; Chen, Kuan Chou; Peng, Chiung-Chi; Peng, Robert Y.

    2015-01-01

    Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) and other flavanoids are extensively used in nutraceuticals because of their antioxidant and antiinflammatory properties. While examining whether GA is effective in alleviating valproic-acid-induced teratogenesis in a chicken embryo model (CEM), we observed embryo hemorrhage and liposis in the musculi longissimus cervicis. We conducted this study to determine whether GA is inherently teratogenic and the extent to which the risk can be transferred to fetuses. A CEM was used to administer GA at 2, 6, 10, and 14 μM. GA at 2 μM did not exhibit cytotoxicity. At 6, 10, and 14 μM, GA caused severe decreases in body and liver weights, causing -5.6%, -21.3%, and -27.5% body weights and 4.0, 3.8, and 3.2-g, liver weights, respectively, in day-1 chicks. The optimal alive birth rate (or damaging rate) reached 33.3%, 39.4%, and 29.2% at 6, 10, and 14 μM GA, respectively. The damaged tissue was primarily cervical muscle (musculi longissimus cervicis), as evidenced by liposis, Zenker’s necrosis, and hemolysis. The erythrocyte, hemoglobin, eosinophil, lymphocyte, and monocyte counts were severely reduced and PPAR-α was downregulated, whereas the Ras/Raf/JAK/STAT pathway was upregulated. The GA dose required to induce teratogenesis was ≥ 6 μM (1.02 mg/kg), which can be easily consumed by pregnant women in typical teas such as Chinese Pu-’Er and Chinese black teas, indicating a potential risk to human fetuses. GA at doses ≥ 1.02 mg/kg of body weight potentially causes characteristic cerebral hemolysis and liposis in the musculi longissimus cervicis. The mechanism of action of GA is multidisciplinary: The liposis can be ascribed to downregulation of PPAR-α; the erythrocyte hemolysis can be attributed to its unique autooxidative and prooxidant behavior and the inhibition of carbonic anhydrase; and the proliferation and differentiation deficits can be attributed to the upregulation of the Ras/Raf/JAK/STAT pathway. PMID

  12. Liver antioxidant stores protect the brain from electromagnetic radiation (900 and 1800 MHz)-induced oxidative stress in rats during pregnancy and the development of offspring.

    Science.gov (United States)

    Çetin, Hasan; Nazıroğlu, Mustafa; Çelik, Ömer; Yüksel, Murat; Pastacı, Nural; Özkaya, Mehmet Okan

    2014-12-01

    The present study determined the effects of mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in the brain and liver as well as the element levels in growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their offspring were equally divided into three different groups: the control, 900 MHz, and 1800 MHz groups. The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/d during pregnancy and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain samples were obtained. Brain and liver glutathione peroxidase activities, as well as liver vitamin A and β-carotene concentrations decreased in the EMR groups, although brain iron, vitamin A, and β-carotene concentrations increased in the EMR groups. In the 6th week, selenium concentrations in the brain decreased in the EMR groups. There were no statistically significant differences in glutathione, vitamin E, chromium, copper, magnesium, manganese, and zinc concentrations between the three groups. EMR-induced oxidative stress in the brain and liver was reduced during the development of offspring. Mobile phone-induced EMR could be considered as a cause of oxidative brain and liver injury in growing rats.

  13. The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men

    Science.gov (United States)

    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

  14. Study of Fe, Zn, Cu, Cd, Pb concentrations in liver, kidney and muscle tissue of cow and sheep marketed in Hamedan in 2011

    Directory of Open Access Journals (Sweden)

    S Sobhanardakani

    2012-11-01

    Full Text Available Importance of heavy metals in food safety and detrimental effects of their high concentrations in food stuff is well documented. In this study, concentrations of Fe, Zn, Cu, Cd and Pb in kidney, liver and muscle tissues of cow and sheep at Hamedan retails were evaluated. A total number of 180 samples was assessed for the amount of heavy metals as ppb in wet weight. For this, wet-digestion method was used to determine the concentration of given elements by ICP (Varian ES-710. Results showed that the highest concentration of heavy metals was determined in the liver and kidney samples, while the lowest concentration was found in muscle tissue. Among the heavy metals, Fe in cow’s liver had the highest concentration (25507±879 ppb and Cd in muscle tissue of sheep has the lowest concentration (192±54 ppb. In overall, accumulation of heavy metals in tissues of cows was higher than sheep. Statistical comparison of accumulated metals concentration in various tissues of these two animal groups showed significant difference (P

  15. Comparative in vitro metabolism of 1-14C-oleic acid and 1-14C-erucic acid in liver, heart and skeletal muscles of rats

    International Nuclear Information System (INIS)

    Bhatia, I.S.; Sharma, A.K.; Ahuja, S.P.

    1978-01-01

    In vitro oxidation of 14 C-oleic and 1- 14 C-erucic acid and their incorporation into lipids by liver, heart and skeletal muscles from female albino rats were studied. These tissues were obtained from rats maintained for 120 days on low fat diet or diets containing 15% mustard oil or 15% groundnut oil. In all these tissues from rats on different types of diets, the oxidation of 1- 14 C-erucic acid was lower than that 1- 14 C-oleic acid. There was little accumulation of lipids in heart after 120 days of feeding mustard oil. Oxidation of 1- 14 C-erucic acid was enhanced in liver, heart and skeletal muscles of rats conditioned to the mustard oil diet supplying erucic acid. Oxidation of erucic acid was maximum in liver and least in heart, whereas there were no differences in the oxidation of 1- 14 C-oleic acid in these tissues. Incorporation of 1- 14 C-oleic acid into triglycerides and phospholipids was not affected by the type of diet or tissues Incorporation of 1- 14 C-erucic acid was mainly into triglycerides of heart and skeletal muscles of rats not accustomed to mustard oil diet whereas these tissues from rats accustomed to mustard oil diets incorporated 1- 14 C-erucic acid both into the triglycerides and phospholipids. (author)

  16. Fatty-acid profiles of white muscle and liver in stream-maturing steelhead trout Oncorhynchus mykiss from early migration to kelt emigration

    Science.gov (United States)

    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.

  17. Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

    Directory of Open Access Journals (Sweden)

    Sabrina Le Bouter

    2010-01-01

    Full Text Available Rosiglitazone (RSG, developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d with untreated non-diabetic littermates (db/+. For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs and free fatty acids (FFAs in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.

  18. Effects of Freshwater Clam Extract Supplementation on Time to Exhaustion, Muscle Damage, Pro/Anti-Inflammatory Cytokines, and Liver Injury in Rats after Exhaustive Exercise

    Directory of Open Access Journals (Sweden)

    Kuang-Wen Liao

    2013-03-01

    Full Text Available The potent anti-inflammatory activities and tissue-protective effects of freshwater clams (Corbicula fluminea have been well reported. The aim of this study was to determine the effects of freshwater clam extract (FCE supplementation on time to exhaustion, muscle damage, pro- and anti-inflammatory cytokines, and liver injury in rats after exhaustive exercise. Thirty-two rats were divided into four groups: sedentary control (SC; SC group with FCE supplementation (SC+FCE; exhaustive exercise (E; and E group with FCE supplementation (E+FCE. The SC+FCE and E+FCE groups were treated with gavage administration of 20 mg/kg for seven consecutive days. Blood samples were collected for the evaluation of biochemical parameters. The cytokine levels of TNF-α and IL-10 were also examined. Twenty-four hours after exhaustive exercise, the rat livers were removed for H & E staining. The FCE supplementation could extend the time to exhaustion in exercised rats. The levels of CPK, LDH, AST, ALT, lactate, TNF-α and H & E stains of the liver injury were significantly decreased in the E+FCE group, but the blood glucose and IL-10 were significantly higher in comparison with the E group. This study suggests that FCE supplementation may improve endurance performance and reduce exercise-induced muscle damage, inflammatory stress and liver injury.

  19. Radioprotection by dipyridamole in the aging mouse. Effects on lipid peroxidation in mouse liver, spleen and brain after whole-body X-ray irradiation

    International Nuclear Information System (INIS)

    Seino, Noritaka

    1995-01-01

    To investigate the radioprotective effect of dipyridamole in the aging mouse, the lipid peroxide content in aging mouse liver, spleen and brain irradiated by X-ray were measured both before and after injection of dipyridamole. The lipid peroxide content increased with aging from 2 months old to 16 months old in the mouse liver, spleen and brain. The content of lipid peroxide in the liver and spleen of the aging mouse was significantly increased in 7 days after whole-body irradiation with 8 Gy, but was unchanged in the brain. Dipyridamole, given before irradiation, significantly inhibited the increase of lipid peroxide after irradiation. These results suggest that dipyridamole may have radioprotective effects on aging mouse liver and spleen as well as on young mouse, and that inhibition of lipid peroxidation is a possible factor in the radioprotective effect of dipyridamole. (author)

  20. Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo.

    Science.gov (United States)

    Zahr, Natalie M; Sullivan, Edith V; Rohlfing, Torsten; Mayer, Dirk; Collins, Amy M; Luong, Richard; Pfefferbaum, Adolf

    2016-07-01

    Serious neurological concomitants of alcoholism include Wernicke's encephalopathy (WE), Korsakoff's syndrome (KS), and hepatic encephalopathy (HE). This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment. Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all three experiments (i.e., liver damage, thiamine deficiency, and food deprivation) were lower than those in baseline or controls. These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.

  1. Distribution of trans-resveratrol and its metabolites after acute or sustained administration in mouse heart, brain, and liver.

    Science.gov (United States)

    Menet, Marie-Claude; Baron, Stephanie; Taghi, Meryam; Diestra, Remi; Dargère, Delphine; Laprévote, Olivier; Nivet-Antoine, Valérie; Beaudeux, Jean-Louis; Bédarida, Tatiana; Cottart, Charles-Henry

    2017-08-01

    Trans-resveratrol is widely studied for its potentially beneficial effects on numerous disorders. It is rapidly metabolized and its metabolites can exhibit biological activity. The present study aimed to investigate whether acute or sustained trans-resveratrol administration impacted on the distribution of trans-resveratrol and its metabolites in brain, heart, and liver. We used ultra-HPLC quadrupole-TOF (UHPLC-Q-TOF) in a full-scan mode to identify and assess large numbers of resveratrol metabolites. For acute intake, mice were overfed with a single dose of trans-resveratrol (150 mg/kg) and organs were collected after 30 and 60 min. For sustained intake, trans-resveratrol was given in the chow (0.04% w/w corresponding to 40 mg/kg/day), and plasma and the organs were collected after 3 months of this resveratrol diet. We found that trans-resveratrol-3-O-glucuronide and resveratrol-3-sulfate were the main metabolites found after acute intake, and free trans-resveratrol (in the brain and heart) and dihydroresveratrol derivatives were found after sustained administration CONCLUSIONS: Our results show notable differences between acute and sustained administration of trans-resveratrol and distribution of trans-resveratrol and its metabolites in mouse heart, brain, and liver. The results suggest a strategy for development of galenic forms of resveratrol. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Effect of prenatal and postnatal microwave exposures on relative activity of SDH of brain and liver in newborn mice

    International Nuclear Information System (INIS)

    Jiang Huai; Yao Gengdong; Zhou Shiyun

    1987-01-01

    Pregnant mice were irradiated with 3 GHz pulse microwave at 8 mW/cm 2 (SAR 3.0-3.5 mW/g) and part of their offspring were irradiated at 1 mW/cm 2 . The effects on the mitochondria marker enzyme SDH of brain and liver in the newborn mice were observed. SDH was quanlitatively determined by microspectrophotometry. The results show that a decrease in the relative activity of SDH in brain was induced by either prenatal or postnatal microwave exposure (p < 0.01). The greatest decrease in the relative activity of SDH occurred in the offspring exposed both prenatally and postnatally. The similar but less changes in the activity of SDH occurred in liver of these mice. The results indicate that the brain SDH is a sensitive index to observe the subtle metabolic alterations which can not be detected using conventional morphologic teratologic procedures. It is suggested that pregnant women should be protected from high power density microwave exposure

  3. Toward the restoration of hand use to a paralyzed monkey: brain-controlled functional electrical stimulation of forearm muscles.

    Directory of Open Access Journals (Sweden)

    Eric A Pohlmeyer

    2009-06-01

    Full Text Available Loss of hand use is considered by many spinal cord injury survivors to be the most devastating consequence of their injury. Functional electrical stimulation (FES of forearm and hand muscles has been used to provide basic, voluntary hand grasp to hundreds of human patients. Current approaches typically grade pre-programmed patterns of muscle activation using simple control signals, such as those derived from residual movement or muscle activity. However, the use of such fixed stimulation patterns limits hand function to the few tasks programmed into the controller. In contrast, we are developing a system that uses neural signals recorded from a multi-electrode array implanted in the motor cortex; this system has the potential to provide independent control of multiple muscles over a broad range of functional tasks. Two monkeys were able to use this cortically controlled FES system to control the contraction of four forearm muscles despite temporary limb paralysis. The amount of wrist force the monkeys were able to produce in a one-dimensional force tracking task was significantly increased. Furthermore, the monkeys were able to control the magnitude and time course of the force with sufficient accuracy to track visually displayed force targets at speeds reduced by only one-third to one-half of normal. Although these results were achieved by controlling only four muscles, there is no fundamental reason why the same methods could not be scaled up to control a larger number of muscles. We believe these results provide an important proof of concept that brain-controlled FES prostheses could ultimately be of great benefit to paralyzed patients with injuries in the mid-cervical spinal cord.

  4. Tissue-specific bioaccumulation of human and veterinary antibiotics in bile, plasma, liver and muscle tissues of wild fish from a highly urbanized region

    International Nuclear Information System (INIS)

    Zhao, Jian-Liang; Liu, You-Sheng; Liu, Wang-Rong; Jiang, Yu-Xia; Su, Hao-Chang; Zhang, Qian-Qian; Chen, Xiao-Wen; Yang, Yuan-Yuan; Chen, Jun; Liu, Shuang-Shuang; Pan, Chang-Gui; Huang, Guo-Yong; Ying, Guang-Guo

    2015-01-01

    We investigated the bioaccumulation of antibiotics in bile, plasma, liver and muscle tissues of wild fish from four rivers in the Pearl River Delta region. In total, 12 antibiotics were present in at least one type of fish tissues from nine wild fish species in the four rivers. The mean values of log bioaccumulation factors (log BAFs) for the detected antibiotics in fish bile, plasma, liver, and muscle tissues were at the range of 2.06–4.08, 1.85–3.47, 1.41–3.51, and 0.48–2.70, respectively. As the digestion tissues, fish bile, plasma, and liver showed strong bioaccumulation ability for some antibiotics, indicating a different bioaccumulation pattern from hydrophobic organic contaminants. Human health risk assessment based on potential fish consumption indicates that these antibiotics do not appear to pose an appreciable risk to human health. To the best of our knowledge, this is first report of bioaccumulation patterns of antibiotics in wild fish bile and plasma. - Highlights: • We investigated the bioaccumulation of antibiotics in wild fish from the Pearl River Delta region. • Twelve antibiotics were found in fish bile, plasma, liver and muscle tissues. • High log bioaccumulation factors suggested strong bioaccumulation ability for some antibiotics in wild fish tissues. • The presence of antibiotics in fish bile and plasma tissues indicates a novel bioaccumulation pattern. • Potential adverse effects are possibly caused by the high internal antibiotic concentrations in tissues. - Fish bile and plasma displayed strong bioaccumulation ability for some antibiotics, indicating a novel bioaccumulation pattern for antibiotics in the contaminated environment

  5. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    DEFF Research Database (Denmark)

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.

    1999-01-01

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  6. The dimethylarginine (ADMA)/nitric oxide pathway in the brain and periphery of rats with thioacetamide-induced acute liver failure: Modulation by histidine.

    Science.gov (United States)

    Milewski, Krzysztof; Hilgier, Wojciech; Albrecht, Jan; Zielińska, Magdalena

    2015-09-01

    Hepatic encephalopathy (HE) is related to variations in the nitric oxide (NO) synthesis and oxidative/nitrosative stress (ONS), and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases (NOSs). In the present study we compared the effects of acute liver failure (ALF) in the rat TAA model on ADMA concentration in plasma and cerebral cortex, and on the activity and expression of the ADMA degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH), in brain and liver. ALF increased blood and brain ADMA, and the increase was correlated with decreased DDAH activity in both brain and liver. An i.p. administration of histidine (His), an amino acid reported to alleviate oxidative stress associated with HE (100 mg/kg b.w.), reversed the increase of brain ADMA, which was accompanied by the recovery of brain DDAH activity (determined ex vivo), and with an increase of the total NOS activity. His also activated DDAH ex vivo in brain homogenates derived from control and TAA rats. ALF in this model was also accompanied by increases of blood cyclooxygenase activity and blood and brain TNF-α content, markers of the inflammatory response in the periphery, but these changes were not affected by His, except for the reduction of TNF-α mRNA transcript in the brain. His increased the total antioxidant capacity of the brain cortex, but not of the blood, further documenting its direct neuroprotective power. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The Mancozeb-containing carbamate fungicide tattoo induces mild oxidative stress in goldfish brain, liver, and kidney.

    Science.gov (United States)

    Atamaniuk, Tetiana M; Kubrak, Olga I; Husak, Viktor V; Storey, Kenneth B; Lushchak, Volodymyr I

    2014-11-01

    Tattoo belongs to the group of carbamate fungicides and contains Mancozeb (ethylene(bis)dithiocarbamate) as its main constituent. The toxicity of Mancozeb to living organisms, particularly fish, is not resolved. This work investigated the effects of 96 h of exposure to 3, 5, or 10 mg L(-1) of Tattoo (corresponding to 0.9, 1.5, or 3 mg L(-1) of Mancozeb) on the levels of oxidative stress markers and the antioxidant enzyme system of brain, liver, and kidney of goldfish, Carassius auratus). In liver, Tattoo exposure resulted in increased activities of superoxide dismutase (SOD) by 70%-79%, catalase by 23%-52% and glutathione peroxidase (GPx) by 49%. The content of protein carbonyls (CP) in liver was also enhanced by 92%-125% indicating extensive damage to proteins. Similar increases in CP levels (by 98%-111%) accompanied by reduced glucose-6-phosphate dehydrogenase activity (by 13%-15%) was observed in kidney of fish exposed to Tattoo; however, SOD activity increased by 37% in this tissue after treatment with 10 mg L(-1) Tattoo. In brain, a rise in lipid peroxide level (by 29%) took place after exposure to 10 mg L(-1) Tattoo and was accompanied by elevation of high-molecular mass thiols (by 14%). Tattoo exposure also resulted in a concentration-dependent decrease in glutathione reductase activity (by 26%-37%) in brain. The data collectively show that exposure of goldfish to 3-10 mg L(-1) of the carbamate fungicide Tattoo resulted in the development of mild oxidative stress and activation of antioxidant defense systems in goldfish tissues. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

  8. Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

    Directory of Open Access Journals (Sweden)

    Han JH

    2015-06-01

    Full Text Available Jin-hong Han,1,2 Hong-zhao Tian,2 Yang-yang Lian,1 Yi Yu,1 Cheng-biao Lu,2 Xin-min Li,3 Rui-ling Zhang,1 Haiyun Xu4 1The Second Affiliated Hospital of Xinxiang Medical University, 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 4The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with

  9. FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting.

    Science.gov (United States)

    Liang, Qingning; Zhong, Ling; Zhang, Jialiang; Wang, Yu; Bornstein, Stefan R; Triggle, Chris R; Ding, Hong; Lam, Karen S L; Xu, Aimin

    2014-12-01

    Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. Heterogeneous binding of sigma radioligands in the rat brain and liver; Possible relationship to subforms of cytochrome P-450

    Energy Technology Data Exchange (ETDEWEB)

    Ross, S B [Research Laboratories, Astra Research Centre AB, Soedertaejle (Sweden)

    1991-01-01

    The binding of four sigma receptor ligands, {sup 3}H-(+)-N-allyl-N-normetazocine ({sup 3}H-(+)-SKF 10,047), {sup 3}H-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ({sup 3}H-(+)-3-PPP), {sup 3}H-haloperidol and {sup 3}H-N,N'-di(o-totyl)guanidine ({sup 3}H-DTG), and the cytochrome P450IID6 ligand and dopamine uptake inhibitor {sup 3}H-1-(2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine ({sup 3}H-GBR 12935) to membranal preparations of rat liver or whole rat brain was examined regarding kinetical properties and inhibition by various compounds with affinity for sigma binding sites or cytochrome P-450. In rat brain the density of binding sites was increased in order (+)-SKF 10,047<(+)-3-PPPliver the corresponding order was (+)-SKF 10,047brain and liver. With the exception of {sup 3}H-(+)-SKF 10,047 there were quite marked differences between the ligands studied. Multiple binding sites were also indicated by the low Hill coefficients found for most of the compounds studied. It was found that the cytochrome P-450 inhibitor proadifen (SKF 525A), like haloperidol, was a potent inhibitor of the binding of {sup 3}H-(+)-SKF 10,047, {sup 3}H-(+)-3-PPP and {sup 3}H-haloperidol to the liver and brain preparations, less active in inhibiting the binding of {sup 3}H-DTG and least effective on the binding of {sup 3}H-GBR 12935. Another cytochrome P-450 inhibitor, L-lobeline, was particularly potent in inhibiting the binding of {sup 3}H-DTG but was also quite potent inhibitor of the binding of the other sigma ligands. It was less potent in inhibiting the binding of {sup 3}H-GBR 12935. The binding of the latter ligand was potently inhibited by the analogous compound GBR 12909 but of the other compounds examined only L-lobeline, proadifen, haloperidol, DTG and (+)-3-PPP had IC50 values below 10 {mu}M. (Abstract Truncated)

  11. Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

    2016-11-15

    Highlights: • Cd induced oxidative stress and immunotoxicity by the generation of ROS. • The toxic effects depended on exposure time and different tissues. • Nrf2 and NF-κB mediated antioxidant and inflammatory responses. • Gene changed at transcriptional, translational, post-translational levels. - Abstract: Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1 mg L{sup −1} Cd for 24 h and 96 h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24 h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained

  12. Effect of mercury dichloride on some biochemical characteristics of brain, blood, and liver in Rutilus caspicus (JAK)

    Energy Technology Data Exchange (ETDEWEB)

    Dokholyan, V K; Akhmedova, T P

    1977-07-12

    Rutilus was subjected to various concentrations of mercury dichloride (100, 10, and 5 micrograms/ml). Brain tissue was then tested to determine nitrogen and carbon metabolism. All the fish in the highest concentration died, while those in the latter groups showed marked changes in metabolism. Ammonia content increased 135% in the first day, then dropped. Data on nitrogen metabolites are presented in two tables. For young fish (1 year), the ammonia content only increased 79%. Protein content in blood was reduced by 20 to 22% within 3 days then started to increase. There was an increase in alpha and beta globulins and a drop in blood sugar and liver glycogen.

  13. IMPACT OF SEVOFLURANE AND ACETYLCYSTEINE ON ISCHEMIA-REPERFUSION INJURY OF THE LIVER FROM BRAIN-DEAD DONOR

    Directory of Open Access Journals (Sweden)

    A. E. Shcherba

    2013-01-01

    Full Text Available Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury. 

  14. Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

    2016-01-01

    Highlights: • Cd induced oxidative stress and immunotoxicity by the generation of ROS. • The toxic effects depended on exposure time and different tissues. • Nrf2 and NF-κB mediated antioxidant and inflammatory responses. • Gene changed at transcriptional, translational, post-translational levels. - Abstract: Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1 mg L"−"1 Cd for 24 h and 96 h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24 h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained

  15. Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio).

    Science.gov (United States)

    Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

    2016-11-01

    Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1mgL -1 Cd for 24h and 96h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained stable at 24 and 96h in the brain. Taken together, we demonstrated Cd-induced oxidative stress and immunotoxicity in fish, possibly through transcriptional regulation of Nrf2 and NF-κB and gene modifications at transcriptional, translational, post-translational levels, which would greatly extend our understanding on the Cd

  16. Hemodynamic measurements in rat brain and human muscle using diffuse near-infrared absorption and correlation spectroscopies

    Science.gov (United States)

    Yu, Guoqiang; Durduran, Turgut; Furuya, D.; Lech, G.; Zhou, Chao; Chance, Britten; Greenberg, J. H.; Yodh, Arjun G.

    2003-07-01

    Measurement of concentration, oxygenation, and flow characteristics of blood cells can reveal information about tissue metabolism and functional heterogeneity. An improved multifunctional hybrid system has been built on the basis of our previous hybrid instrument that combines two near-infrared diffuse optical techniques to simultaneously monitor the changes of blood flow, total hemoglobin concentration (THC) and blood oxygen saturation (StO2). Diffuse correlation spectroscopy (DCS) monitors blood flow (BF) by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave spectroscopy (DPDW) measures tissue absorption and scattering. Higher spatial resolution, higher data acquisition rate and higher dynamic range of the improved system allow us to monitor rapid hemodynamic changes in rat brain and human muscles. We have designed two probes with different source-detector pairs and different separations for the two types of experiments. A unique non-contact probe mounted on the back of a camera, which allows continuous measurements without altering the blood flow, was employed to in vivo monitor the metabolic responses in rat brain during KCl induced cortical spreading depression (CSD). A contact probe was used to measure changes of blood flow and oxygenation in human muscle during and after cuff occlusion or exercise, where the non-contact probe is not appropriate for monitoring the moving target. The experimental results indicate that our multifunctional hybrid system is capable of in vivo and non-invasive monitoring of the hemodynamic changes in different tissues (smaller tissues in rat brain, larger tissues in human muscle) under different conditions (static versus moving). The time series images of flow during CSD obtained by our technique revealed spatial and temporal hemodynamic changes in rat brain. Two to three fold longer recovery times of flow and oxygenation after cuff occlusion or exercise from calf flexors in a

  17. Cadmium concentration in liver and muscle of silky shark (Carcharhinus falciformis) in the tip of Baja California south, México

    International Nuclear Information System (INIS)

    Terrazas-López, Rafael; Arreola-Mendoza, Laura; Galván-Magaña, Felipe; Anguiano-Zamora, Marlene; Sujitha, S.B.; Jonathan, M.P.

    2016-01-01

    Cadmium concentrations were determined in the tissues of muscle and liver of Carcharhinus falciformis (silky shark) sampled in Todos Santos, Baja California South, Mexico. This is one of the main shark species for human consumption in Mexico. Results indicate that accumulation of Cd varied in both sexes, based on its metabolism, sex, maturity and other biological characteristics. High Cd values were observed in the liver of adults of male (529.61 μg g −1 ) and female (457.43 μg g −1 ), whereas, in muscular tissues it was low (0.37 μg g −1 ) than the prescribed permissible limits for seafood (0.5 μg g −1 ). Substantial correlations were observed between body length and Cd values in adults except young male due to faster growth rate and its metabolism. The study indicated the impact of environmental conditions in the accumulation of Cd and its risk to the food web structure in the marine environment and health hazard for humans. - Highlights: •Cadmium in liver and muscle of silky shark, Mexico. •Accumulation is based on its metabolism, sex, maturity and biological characteristics. •Health hazard for humans and it is a risk to the food web structure.

  18. Damage to Liver and Skeletal Muscles in Marathon Runners During a 100 km Run With Regard to Age and Running Speed

    Directory of Open Access Journals (Sweden)

    Jastrzębski Zbigniew

    2015-03-01

    Full Text Available The purpose of this study was to determine: (1 whether damage to liver and skeletal muscles occurs during a 100 km run; (2 whether the metabolic response to extreme exertion is related to the age or running speed of the participant; (3 whether it is possible to determine the optimal running speed and distance for long-distance runners’ health by examining biochemical parameters in venous blood. Fourteen experienced male amateur ultra-marathon runners, divided into two age groups, took part in a 100 km run. Blood samples for liver and skeletal muscle damage indexes were collected from the ulnar vein just before the run, after 25, 50, 75 and 100 km, and 24 hours after termination of the run. A considerable increase in alanine aminotransferase (ALT and aspartate aminotransferase (AST was observed with the distance covered (p < 0.05, which continued during recovery. An increase in the mean values of lactate dehydrogenase (LDH, creatine kinase (CK and C-reactive protein (CRP (p < 0.05 was observed with each sequential course. The biggest differences between the age groups were found for the activity of liver enzymes and LDH after completing 75 km as well as after 24 hours of recovery. It can be concluded that the response to extreme exertion deteriorates with age in terms of the active movement apparatus.

  19. In cirrhotic patients reduced muscle strength is unrelated to muscle capacity for ATP turnover suggesting a central limitation

    DEFF Research Database (Denmark)

    Gam, Christiane Marie Bourgin; Nielsen, H B; Secher, Niels H.

    2011-01-01

      We investigated whether in patients with liver cirrhosis reduced muscle strength is related to dysfunction of muscle mitochondria.......  We investigated whether in patients with liver cirrhosis reduced muscle strength is related to dysfunction of muscle mitochondria....

  20. Bioaccumulation of mercury, cadmium, zinc, chromium, and lead in muscle, liver, and spleen tissues of a large commercially valuable catfish species from Brazil

    Directory of Open Access Journals (Sweden)

    Fábio P. Arantes

    2016-03-01

    Full Text Available The increasing amounts of heavy metals entering aquatic environments can result in high accumulation levels of these contaminants in fish and their consumers, which pose a serious risk to ecosystems and human health. We investigated the concentrations of mercury (Hg, cadmium (Cd, zinc (Zn, chromium (Cr, and lead (Pb in muscle, liver, and spleen tissues of Pseudoplatystoma corruscans specimens collected from two sites on the Paraopeba River, Brazil. The level of heavy metals concentrations in the tissues was often higher in viscera (i.e. liver and spleen than in muscle, and thus, the viscera should not be considered for human consumption. Correlations between metal concentrations and fish size were not significant. Although the levels of muscle bioaccumulation of Hg, Cd, Zn, Cr, and Pb, generally do not exceed the safe levels for human consumption, the constant presence of heavy metals in concentrations near those limits considered safe for human consumption, is a reason for concern, and populations who constantly consume fish from polluted rivers should be warned. Our findings also indicate that in a river network where certain areas are connected to other areas with high rates of environmental pollutants, people should be cautious about the regular consumption of fish, even when the fish consumed are caught in stretches of the basin where contamination levels are considered low, since many of the freshwater fish with high commercial value, such as the catfish surubim, are migratory.

  1. Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

    Directory of Open Access Journals (Sweden)

    Bruno dos Santos

    2013-01-01

    Full Text Available This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet; soybean oil (S; lard (L; and hydrogenated vegetable fat (H. We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver.

  2. An analysis of the effects of Mn2+ on oxidative phosphorylation in liver, brain, and heart mitochondria using state 3 oxidation rate assays

    International Nuclear Information System (INIS)

    Gunter, Thomas E.; Gerstner, Brent; Lester, Tobias; Wojtovich, Andrew P.; Malecki, Jon; Swarts, Steven G.; Brookes, Paul S.; Gavin, Claire E.; Gunter, Karlene K.

    2010-01-01

    Manganese (Mn) toxicity is partially mediated by reduced ATP production. We have used oxidation rate assays-a measure of ATP production-under rapid phosphorylation conditions to explore sites of Mn 2+ inhibition of ATP production in isolated liver, brain, and heart mitochondria. This approach has several advantages. First, the target tissue for Mn toxicity in the basal ganglia is energetically active and should be studied under rapid phosphorylation conditions. Second, Mn may inhibit metabolic steps which do not affect ATP production rate. This approach allows identification of inhibitions that decrease this rate. Third, mitochondria from different tissues contain different amounts of the components of the metabolic pathways potentially resulting in different patterns of ATP inhibition. Our results indicate that Mn 2+ inhibits ATP production with very different patterns in liver, brain, and heart mitochondria. The primary Mn 2+ inhibition site in liver and heart mitochondria, but not in brain mitochondria, is the F 1 F 0 ATP synthase. In mitochondria fueled by either succinate or glutamate + malate, ATP production is much more strongly inhibited in brain than in liver or heart mitochondria; moreover, Mn 2+ inhibits two independent sites in brain mitochondria. The primary site of Mn-induced inhibition of ATP production in brain mitochondria when succinate is substrate is either fumarase or complex II, while the likely site of the primary inhibition when glutamate plus malate are the substrates is either the glutamate/aspartate exchanger or aspartate aminotransferase.

  3. Comparative protective effects of royal jelly and cod liver oil against neurotoxic impact of tartrazine on male rat pups brain.

    Science.gov (United States)

    Mohamed, Amany Abdel-Rahman; Galal, Azza A A; Elewa, Yaser H A

    2015-09-01

    This study is aimed to evaluate the possible neurotoxic effect of tartrazine (T), an extensively used synthetic azo dye, as well as to determine the potential modulatory role of cod liver oil (CLO) or royal jelly (RJ) against such effects. For this purpose, thirty-six male rat pups were allocated into six groups. The 1st group received distilled water (control group), the 2nd group was given 300 mg RJ/kg bw (RJ group), the 3rd group was given 0.4 ml CLO/kg bw (CLO group), the 4th was given 500 mg T/kg bw (T group). The 5th group was given T concurrently with RJ (TRJ group) and the 6th group was given T concurrently with CLO (TCLO group), at the same doses as the former groups. All treatments were given orally for 30 consecutive days. The concentrations of different brain neurotransmitters, gamma amino butyric acid (GABA), dopamine (DA) and serotonin (5HT) as well as the antioxidant and oxidative stress biomarkers were measured in the brain homogenates. An immunohistochemical staining of the cerebral cortex was applied with the anti-ssDNA antibody (an apoptotic cell marker) to reveal the changes in brain structure. The T group revealed a significant decrease in the concentration of the brain neurotransmitters, a sharp shortage in the level of antioxidant biomarkers (super oxide dismutase, catalase and the reduced glutathione), a marked increase in malondialdehyde levels, and numerous apoptotic cells in the brain cortex compared with the other groups. Interestingly, all the previously mentioned parameters were almost retrieved in both the TRJ and TCLO groups compared to the T group. These results conclusively demonstrate that RJ and CLO administration provides sufficient protection against the ruinous effects of T on rat pups brain tissue function and structure. Copyright © 2015 Elsevier GmbH. All rights reserved.

  4. Interaction of red pepper (Capsicum annum, Tepin) polyphenols with Fe(II)-induced lipid peroxidation in brain and liver

    International Nuclear Information System (INIS)

    Oboh, G.; Rocha, J.B.T.

    2006-03-01

    Polyphenols exhibit a wide range of biological effects because of their antioxidant properties. Several types of polyphenols (phenolic acids, hydrolyzable tannins, and flavonoids) show anticarcinogenic and antimutagenic effects. Comparative studies were carried on the protective ability of free and bound polyphenol extracts of red Capsicum annuum Tepin (CAT) on brain and liver - In vitro. Free polyphenols of red Capsicum annuum Tepin (CAT) were extracted with 80% acetone, while the bound polyphenols were extracted with ethyl acetate from acid and alkaline hydrolysis of the pepper residue from free polyphenols extract. The phenol content, Fe (II) chelating ability, OH radical scavenging ability and protective ability of the extract against Fe (II)-induced lipid peroxidation in brain and liver was subsequently determined. The results of the study revealed that the free polyphenols (218.2mg/100g) content of the pepper were significantly higher than the bound polyphenols (42.5mg/100g). Furthermore, the free polyphenol extract had a significantly higher ( 2+ induced lipid peroxidation, and this is probably due to the higher Fe (II) chelating ability and OH radical scavenging ability of the free polyphenols from the pepper. (author)

  5. Molecular modifications of cholesterol metabolism in the liver and the brain after chronic contamination with cesium 137.

    Science.gov (United States)

    Racine, R; Grandcolas, L; Grison, S; Gourmelon, P; Guéguen, Y; Veyssière, G; Souidi, M

    2009-07-01

    Twenty years after Chernobyl accident, the daily ingestion of foodstuff grown on contaminated grounds remains the main source for internal exposure to ionizing radiations, and primarily to cesium 137 ((137)Cs). Though the effects of a long-term internal contamination with radionuclides are poorly documented, several non-cancerous pathologies have been described in this population. However, lipid metabolism was never investigated after chronic internal contamination although disturbances were observed in externally-exposed people. In this regard, we assessed the effects of a chronic ingestion of (137)Cs on hepatic and cerebral cholesterol metabolism. To mimic a chronically-exposed population, rats were given (137)Cs-supplemented water at a post-accidental dose (150 Bq/rat/day) during 9 months. The plasma profile, and brain and liver cholesterol concentrations were unchanged. A decrease of ACAT 2, Apo E, and LXRmRNA levels was recorded in the liver. In the brain, a decrease of CYP27A1 and ACAT 1 gene expression was observed. These results clearly show that cholesterol metabolism is not disrupted by a chronic ingestion of (137)Cs, although several molecular alterations are observed. This work would be interestingly completed by studying the influence of (137)Cs in models likely more sensitive to contaminants, such as the fetus or individuals susceptible to a lipidic disease.

  6. Effects of an Agaricus blazei Aqueous Extract Pretreatment on Paracetamol-Induced Brain and Liver Injury in Rats

    Directory of Open Access Journals (Sweden)

    Andréia A. Soares

    2013-01-01

    Full Text Available The action of an Agaricus blazei aqueous extract pretreatment on paracetamol injury in rats was examined not only in terms of the classical indicators (e.g., levels of hepatic enzymes in the plasma but also in terms of functional and metabolic parameters (e.g., gluconeogenesis. Considering solely the classical indicators for tissue damage, the results can be regarded as an indication that the A. blazei extract is able to provide a reasonable degree of protection against the paracetamol injury in both the hepatic and brain tissues. The A. blazei pretreatment largely prevented the increased levels of hepatic enzymes in the plasma (ASP, ALT, LDH, and ALP and practically normalized the TBARS levels in both liver and brain tissues. With respect to the functional and metabolic parameters of the liver, however, the extract provided little or no protection. This includes morphological signs of inflammation and the especially important functional parameter gluconeogenesis, which was impaired by paracetamol. Considering these results and the long list of extracts and substances that are said to have hepatoprotective effects, it would be useful to incorporate evaluations of functional parameters into the experimental protocols of studies aiming to attribute or refute effective hepatoprotective actions to natural products.

  7. Inhibition of lipid peroxidation induced by γ- radiation and AAPH in rat liver and brain mitochondria by mushrooms

    International Nuclear Information System (INIS)

    Lakshmi, B.; Janardhanan, K.K.; Tilak, J.C.; Devasagayam, T.P.A.; Adhikari, S.

    2005-01-01

    Exposure to radiation or 2.2' Azobis(2-amidopropane) dihydrochloride (AAPH) induces generation of reactive oxygen species (ROS) especially hydroxyl radical ( . OH) and peroxyl radical (ROO . ), which are capable of inducing lipid peroxidation. Our earlier studies have demonstrated that extracts of the medicinal and edible mushrooms Ganoderma lucidum, Pleurotus florida, Pleurotus sajor-caju and Phellinus rimosus possessed significant antioxidant activity, measured as radical scavenging. In the present study, we examined the protective effect of these mushroom extracts against radiation- and AAPH-induced lipid peroxidation using rat liver and brain mitochondria as model systems. The results obtained showed that the investigated mushroom extracts significantly inhibited the formation of lipid hydroperoxide and thiobarbituric acid reactive substances, indicating membrane protective effects. The finding suggests the profound protective effect of the extracts of the fruiting bodies of G. lucidum, P. florida, P. sajor-caju and P. rimosus against lipid peroxidation by two major forms of ROS capable of inducing this type of damage in a major organelle, the mitochondria from both rat liver and brain. This observation can possibly explain the health benefits of these mushrooms. (author)

  8. Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

    Science.gov (United States)

    Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

    2017-01-01

    Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

  9. Altered Function and Expression of ABC Transporters at the Blood–Brain Barrier and Increased Brain Distribution of Phenobarbital in Acute Liver Failure Mice

    Directory of Open Access Journals (Sweden)

    Li Liu

    2018-03-01

    Full Text Available This study investigated alterations in the function and expression of P-glycoprotein (P-GP, breast cancer resistance protein (BCRP, and multidrug resistance-associated protein 2 (MRP2 at the blood–brain barrier (BBB of acute liver failure (ALF mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl-S-glutathione, respectively. The mRNA and proteins expression levels of P-GP, BCRP, and MRP2 were evaluated with quantitative real-time PCR and western blot, respectively. MDCK-MDR1 and HCMEC/D3 cells were used to document the effects of the abnormally altered components in serum of ALF mice on the function and expression of P-GP. The clinical significance of alteration in P-GP function and expression was investigated by determining the distribution of the P-GP substrate phenobarbital (60 mg/kg, intravenous administration in the brain and loss of righting reflex (LORR induced by the drug (100 mg/kg. The results showed that ALF significantly downregulated the function and expression of both P-GP and BCRP, but increased the function and expression of MRP2 in the brain of mice. Cell study showed that increased chenodeoxycholic acid may be a reason behind the downregulated P-GP function and expression. Compared with control mice, ALF mice showed a significantly higher brain concentration of phenobarbital and higher brain-to-plasma concentration ratios. In accordance, ALF mice showed a significantly larger duration of LORR and shorter latency time of LORR by phenobarbital, inferring the enhanced pharmacological effect of phenobarbital on the central nervous system (CNS. In conclusion, the function and expression of P-GP and BCRP decreased, while the function and expression of MRP2 increased in the brain of ALF mice. The attenuated function and expression

  10. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

    International Nuclear Information System (INIS)

    Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

    2004-01-01

    The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16 INKa and DNA repair gene O 6 -methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16 INKa promoter methylation upon LDR exposure. In male liver tissue, p16 INKa promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16 INKa promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16 INKa and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure

  11. The effects of fasting and cold exposure on metabolic rate and mitochondrial proton leak in liver and skeletal muscle of an amphibian, the cane toad Bufo marinus.

    Science.gov (United States)

    Trzcionka, M; Withers, K W; Klingenspor, M; Jastroch, M

    2008-06-01

    Futile cycling of protons across the mitochondrial inner membrane contributes significantly to standard metabolic rate in a variety of ectothermic and endothermic animals, but adaptations of the mitochondrial bioenergetics to different environmental conditions have rarely been studied in ectotherms. Changes in ambient temperature and nutritional status have a great effect on the physiological demands of ectothermic amphibians and may require the adjustment of mitochondrial efficiency. In order to investigate the effect of temperature and nutritional status on the mitochondrial level, we exposed male cane toads to either 10 degrees C or 30 degrees C and fasted half of the animals in each group. Cold exposure resulted in a fourfold reduction of the resting metabolic rate whereas nutritional status had only minor effects. The mitochondrial adjustments to each condition were observed by comparing the proton leak kinetics of isolated liver and skeletal muscle mitochondria at 25 degrees C. In response to cold exposure, liver mitochondria showed a decrease in proton conductance while skeletal muscle mitochondria were unchanged. Additional food deprivation had minor effects in skeletal muscle, but in liver we uncovered surprising differences in energy saving mechanisms between the acclimation temperatures: in warm-acclimated toads, fasting resulted in a decrease of the proton conductance whereas in cold-acclimated toads, the activity of the respiratory chain was reduced. To investigate the molecular mechanism underlying mitochondrial proton leakage, we determined the adenine-nucleotide transporter (ANT) content, which explained tissue-specific differences in the basal proton leak, but neither the ANT nor uncoupling protein (UCP) gene expression correlated with alterations of the proton leak in response to physiological stimuli.

  12. Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis

    DEFF Research Database (Denmark)

    Praktiknjo, Michael; Book, Marius; Luetkens, Julian

    2018-01-01

    of sarcopenia using magnetic resonance imaging (MRI) in decompensated cirrhotic patients with transjugular intrahepatic portosystemic shunt (TIPS). METHODS: The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the fat-free muscle area (FFMA) in 116...... in a validation cohort of 45 patients. RESULTS: FFMA correlated with follistatin and TPMT and showed slightly better association with survival than TPMT. Gender-specific cut-off values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS...... in the sarcopenia group but resolved in the non-sarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute-on-chronic liver failure (ACLF). FFMA was an independent predictor of survival in these patients. CONCLUSION: This study...

  13. Muscle insulin binding and plasma levels in relation to liver glucokinase activity, glucose metabolism and dietary carbohydrates in rainbow trout.

    Science.gov (United States)

    Capilla, Encarnación; Médale, Françoise; Navarro, Isabel; Panserat, Stéphane; Vachot, Christiane; Kaushik, Sadasivam; Gutiérrez, Joaquim

    2003-01-31

    Rainbow trout were fed for 10 weeks with either a carbohydrate-free diet (C-free) or with four experimental diets containing various levels (20 or 40%) and sources of starch (extruded wheat or peas) in order to examine metabolic utilisation of dietary vegetable carbohydrates and its endocrine control. The study was focused on the parameters described as limiting in glucose metabolism in fish. Feeding trials were conducted at 8 and 18 degrees C to establish whether carbohydrate-rich diets can be used in trout farming irrespective of water temperature. At both temperatures, pea diets (especially the highest level) resulted in a feed efficiency as high as the C-free diet. Fish had similar growth rates except when fed the low wheat content diet. Glycaemia values 6 h after feeding were significantly higher in trout fed carbohydrate diets than those given the C-free diet, whereas plasma insulin levels were similar independently of the levels of dietary starch. This study provides the first evidence that glucokinase (GK) activity and mRNA level in trout liver increase in proportion to the content of dietary starch. Nevertheless, these changes were not correlated with plasma insulin levels. Insulin-like growth factor-I (IGF-I) binding and number of receptors in skeletal muscle were consistently higher than those for insulin but no diet-induced differences were found for any of these parameters. Temperature clearly affected the postprandial profile of glucose and insulin, which both showed lower levels 6 h after feeding at 8 degrees C than at 18 degrees C, which was consistent with a lower feed intake. Glucose and insulin levels decreased markedly 24 h after feeding at 18 degrees C, while they were still high at 8 degrees C, an observation concordant with delayed transit rate. These findings indicate satisfactory adaptation of rainbow trout to diets with a relatively high vegetable starch content, especially when provided as extruded peas, and indicate that diets with

  14. Polydatin attenuates d-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice.

    Science.gov (United States)

    Xu, Lie-Qiang; Xie, You-Liang; Gui, Shu-Hua; Zhang, Xie; Mo, Zhi-Zhun; Sun, Chao-Yue; Li, Cai-Lan; Luo, Dan-Dan; Zhang, Zhen-Biao; Su, Zi-Ren; Xie, Jian-Hui

    2016-11-09

    Accumulating evidence has shown that chronic injection of d-galactose (d-gal) can mimic natural aging, with accompanying liver and brain injury. Oxidative stress and apoptosis play a vital role in the aging process. In this study, the antioxidant ability of polydatin (PD) was investigated using four established in vitro systems. An in vivo study was also conducted to investigate the possible protective effect of PD on d-gal-induced liver and brain damage. The results showed that PD had remarkable in vitro free radical scavenging activity on 2,2-diphenyl-1-picryl-hydrazyl (DPPH˙), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS + ˙) radical ions, and hydroxyl and superoxide anions. Results in vivo indicated that, in a group treated with d-gal plus PD, PD remarkably decreased the depression of body weight and organ indexes, reduced the levels of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated alterations in liver and brain histopathology. PD also significantly decreased the level of MDA and elevated SOD, GSH-Px, CAT activity and T-AOC levels in the liver and brain. In addition, the levels of inflammatory mediators, such as TNF-α, IL-1β and IL-6 in serum were markedly reduced after PD treatment. Western blotting results revealed that PD treatment noticeably attenuated the d-gal-induced elevation of Bcl-2/Bax ratio and caspase-3 protein expression in liver and brain. Overall, our findings indicate that PD treatment could effectively attenuate d-gal-induced liver and brain damage, and the mechanism might be associated with decreasing the oxidative stress, inflammation and apoptosis caused by d-gal. PD holds good potential for further development into a promising pharmaceutical candidate for the treatment of age-associated diseases.

  15. 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.

    Science.gov (United States)

    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 mass index (P 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.

  16. O2 supplementation to secure the near-infrared spectroscopy determined brain and muscle oxygenation in vascular surgical patients

    DEFF Research Database (Denmark)

    Rokamp, Kim Z; Secher, Niels H; Eiberg, Jonas

    2014-01-01

    This study addresses three questions for securing tissue oxygenation in brain (rScO2) and muscle (SmO2) for 100 patients (age 71 ± 6 years; mean ± SD) undergoing vascular surgery: (i) Does preoxygenation (inhaling 100% oxygen before anesthesia) increase tissue oxygenation, (ii) Does inhalation...... of 70% oxygen during surgery prevent a critical reduction in rScO2 (patients and the intraoperative inspired oxygen fraction was set to 0.70 while tissue...... oxygenation was determined by INVOS 5100C. Preoxygenation increased rScO2 (from 65 ± 8 to 72 ± 9%; P patients. Following anesthesia and tracheal intubation an eventual change...

  17. Lipopolysaccharide precipitates hepatic encephalopathy and increases blood-brain barrier permeability in mice with acute liver failure.

    Science.gov (United States)

    Chastre, Anne; Bélanger, Mireille; Nguyen, Bich N; Butterworth, Roger F

    2014-03-01

    Acute liver failure (ALF) is frequently complicated by infection leading to precipitation of central nervous system complications such as hepatic encephalopathy (HE) and increased mortality. There is evidence to suggest that when infection occurs in ALF patients, the resulting pro-inflammatory mechanisms may be amplified that could, in turn, have a major impact on blood-brain barrier (BBB) function. The aim of this study was to investigate the role of endotoxemia on the progression of encephalopathy in relation to BBB permeability during ALF. Adult male C57-BL6 mice with ALF resulting from azoxymethane-induced toxic liver injury were administered trace amounts of the endotoxin component lipopolysaccharide (LPS). Effects on the magnitude of the systemic inflammatory response, liver pathology and BBB integrity were measured as a function of progression of HE, defined as time to loss of corneal reflex (coma). Lipopolysaccharide caused additional two- to seven-fold (P liver pathology and associated increases of circulating transaminases as well as increased hyperammonaemia consistent with a further loss of viable hepatocytes. LPS treatment of ALF mice led to a rapid precipitation of hepatic coma and the BBB became permeable to the 25-kDa protein immunoglobulin G (IgG). This extravasation of IgG was accompanied by ignificant up-regulation of matrix metalloproteinase-9 (MMP-9), an endopeptidase known to modulate opening of the BBB in a wide range of neurological disorders. These findings represent the first direct evidence of inflammation-related BBB permeability changes in ALF. © 2013 John Wiley & Sons A/S. Publishing by John Wiley & Sons Ltd.

  18. Apoptotic Effects of Reduced Brain Derived Neurotrophic Factor (BDNF on Mouse Liver and Kidney

    Directory of Open Access Journals (Sweden)

    Berna Tezcan

    2017-12-01

    Full Text Available Objective: Brainderived neurotrophic factor (BDNF promotes the development and differentiation of neurons and synapses, as well as neuronal survival, by acting on specific neuronal groups in the central and peripheral nervous systems. However, the direct effect of BDNF on apoptosis in peripheral tissues is not known. The aim of this study was to investigate the relationship between BDNF and apoptosis, and the density and distribution of BDNF receptors in liver and kidney tissues by histological and immunehistochemical methods. Methods: Seven wild-type and 7 BDNF heterozygous (reduced BDNF levels male mice were used in the study. Caspase-3 and TUNEL immunehistochemical stainings were performed in order to investigate the presence of apoptosis in the liver and kidney tissues of the studied groups. Apoptosis-entering cells were counted and the groups were compared. Concentration and distribution of BDNF receptors, tropomyosin-related kinase B (TrkB and nerve growth factor receptor p75 (NGFR p75, in liver and kidney tissues were also examined by immunehistochemical analyzes. Results: As a result of Caspase-3 and TUNEL immune histochemical staining, more cells were counted to enter the apoptotic process in sections of BDNF heterozygous group compared to control group (p<0.0001. In both groups TrkB and NGFR p75 receptors in liver and kidney tissues were determined in trace amounts, but there was no difference in intensity and distribution between the studied groups. Conclusion: According to our histological and immune histochemical stainings and statistical analysis of cell count between groups, it was found that BDNF is protect ive against apoptosis in liver and kidney. The lack of difference between the studied groups in terms of intensity and distribution of BDNF receptors, suggests that BDNF receptor distribution in the liver and kidney tissues may be different from the nervous system or that BDNF may differ in affinity for these receptors.

  19. Influence of electromagnetic field (1800 MHz on lipid peroxidation in brain, blood, liver and kidney in rats

    Directory of Open Access Journals (Sweden)

    Paweł Bodera

    2015-08-01

    Full Text Available Objectives: The aim of this study is the evaluation of the influence of repeated (5 times for 15 min exposure to electromagnetic field (EMF of 1800 MHz frequency on tissue lipid peroxidation (LPO both in normal and inflammatory state, combined with analgesic treatment. Material and Methods: The concentration of malondialdehyde (MDA as the end-product of the lipid peroxidation (LPO was estimated in blood, liver, kidneys, and brain of Wistar rats, both healthy and those with complete Freund’s adjuvant (CFA-induced persistent paw inflammation. Results: The slightly elevated levels of the MDA in blood, kidney, and brain were observed among healthy rats in electromagnetic field (EMF-exposed groups, treated with tramadol (TRAM/EMF and exposed to the EMF. The malondialdehyde remained at the same level in the liver in all investigated groups: the control group (CON, the exposed group (EMF, treated with tramadol (TRAM as well as exposed to and treated with tramadol (TRAM/EMF. In the group of animals treated with the complete Freund’s adjuvant (CFA we also observed slightly increased values of the MDA in the case of the control group (CON and the exposed groups (EMF and TRAM/EMF. The MDA values concerning kidneys remained at the same levels in the control, exposed, and not-exposed group treated with tramadol. Results for healthy rats and animals with inflammation did not differ significantly. Conclusions: The electromagnetic field exposure (EMF, applied in the repeated manner together with opioid drug tramadol (TRAM, slightly enhanced lipid peroxidation level in brain, blood, and kidneys.

  20. Insulin-like growth factor-II (IGF II) receptor from rat brain is of lower apparent molecular weight than the IGF II receptor from rat liver

    International Nuclear Information System (INIS)

    McElduff, A.; Poronnik, P.; Baxter, R.C.

    1987-01-01

    The binding subunits of the insulin and insulin-like growth factor-I (IGF I) receptors from rat brain are of lower molecular weight than the corresponding receptor in rat liver, possibly due to variations in sialic acid content. We have compared the IGF II receptor from rat brain and rat liver. The brain receptor is of smaller apparent mol wt (about 10 K) on sodium dodecyl sulfate polyacrylamide gel electrophoresis. This size difference is independent of ligand binding as it persists in iodinated and specifically immunoprecipitated receptors. From studies of wheat germ agglutinin binding and the effect of neuraminidase on receptor mobility, we conclude that this difference is not simply due to variations in sialic acid content. Treatment with endoglycosidase F results in reduction in the molecular size of both liver and brain receptors and after this treatment the aglycoreceptors are of similar size. We conclude that in rat brain tissue the IGF II receptor like the binding subunits of the insulin and IGF I receptors is of lower molecular size than the corresponding receptors in rat liver. This difference is due to differences in N-linked glycosylation

  1. Expiratory muscle control during vomiting - Role of brain stem expiratory neurons

    Science.gov (United States)

    Miller, A. D.; Tan, L. K.

    1987-01-01

    The neural mechanisms controlling the muscles involved during vomiting were examined using decerebrated cats. In one experiment, the activity of the ventral respiratory group (VRG) expiratory (E) neurons was recorded during induced 'fictive vomiting' (i.e., a series of bursts of coactivation of abdominal and phrenic nerves that would be expected to produce expulsion in unparalyzed animals) and vomiting. In a second, abdominal muscle electromyographic and nerve activity were compared before and after sectioning the axons of descending VRG E neurons as they cross the midline between C1 and the obex (the procedure that is known to abolish expiratory modulation of internal intercostal muscle activity). The results of the study indicate that the abdominal muscles are controlled differently during respiration and vomiting.

  2. LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β

    OpenAIRE

    Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

    2012-01-01

    Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer’s disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-...

  3. Apoptosis Induced in The Brain and Liver of Fetuses And Placenta of Irradiated Pregnant Rats Treated With Antacid Containing Aluminum

    International Nuclear Information System (INIS)

    Ramadan, F.L.; Madkour, N.K.

    2012-01-01

    Aluminum (Al) is widely used in antacid medicine which frequently used by pregnant women. It is of great importance to increase the knowledge about its harmful effects on the fetuses. The present study clarified that administration of antacid containing Al and/or exposure to gamma radiation induced maternal and fetal detrimental impact. Pregnant albino rats were administered antacid containing Al on the gestational days 5th, 7th, 9th, 11th, 13th, 15th and 17th at a dose of 4.5 mg/g and exposed to whole body fractionated gamma radiation (2 Gy) at a dose of 0.5 Gy for 4 times on gestational days 6th, 8th, 10th and 12th of pregnancy. Morphological, biochemical and molecular changes were studied. The investigation was carried out one day prior to parturition (the 20th day of gestation). Antacid containing Al and/or radiation induced growth retardation, intrauterine death, malformations and embryonic resorption. The extent of lipid peroxidase formation as well as glutathione content in the brain and liver tissues of rat fetuses and placenta of pregnant rats were used as sensitive parameters to evaluate tissues damage. Antacid containing Al and/or radiation treatment resulted in decreased total protein content in the maternal placenta tissue. Moreover, the elevation in the lipid peroxidase (malondialdehyde; MDA) was accompanied with decline in the glutathione content (GSH) in the brain and liver tissues of rat fetuses. The activity of a key enzyme of apoptosis namely the caspase-3 was analyzed, which its activation represent a point of no return in apoptosis induction. Apoptosis was confirmed by another important hallmark of programmed cell death such as the DNA fragmentation. Treatment with antacid containing Al and/or gamma irradiation significantly increased caspase-3 activity and DNA fragmentation in maternal placental tissue and fetal brain and liver tissues as compared to control animals. In conclusion, the present investigation showed that the deleterious

  4. Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS Horses

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2018-01-01

    Full Text Available Nowadays, endocrine disorders have become more frequent in both human and veterinary medicine. In horses, reduced physical activity combined with carbohydrate and sugar overload may result in the development of the so-called equine metabolic syndrome (EMS. EMS is characterized by insulin resistance, hyperinsulinemia, elevated blood triglyceride concentrations and usually obesity. Although the phenotypic features of EMS individuals are well known, the molecular mechanism underlying disease development remains elusive. Therefore, in the present study, we analyzed insulin-sensitive tissues, i.e., muscles, liver and adipose tissue in order to evaluate insulin resistance and apoptosis. Furthermore, we assessed mitochondrial dynamics and mitophagy in those tissues, because mitochondrial dysfunction is linked to the development of metabolic syndrome. We established the expression of genes related to insulin resistance, endoplasmic reticulum (ER stress and mitochondria clearance by mitophagy using RT-PCR and Western blot. Cell ultrastructure was visualized using electron transmission microscopy. The results indicated that adipose tissue and liver of EMS horses were characterized by increased mitochondrial damage and mitophagy followed by triggering of apoptosis as mitophagy fails to restore cellular homeostasis. However, in muscles, apoptosis was reduced, suggesting the existence of a protective mechanism allowing that tissue to maintain homeostasis.

  5. Regulation of p53 by reversible post-transcriptional and post-translational mechanisms in liver and skeletal muscle of an anoxia tolerant turtle, Trachemys scripta elegans.

    Science.gov (United States)

    Zhang, Jing; Biggar, Kyle K; Storey, Kenneth B

    2013-01-15

    The red-eared slider turtle (Trachemys scripta elegans) exhibits well-developed natural anoxia tolerance that depends on multiple biochemical adaptations, including anoxia-induced hypometabolism. We hypothesized that signaling by the p53 protein could aid in establishing the hypometabolic state by arresting the cell cycle, protecting against DNA damage as well as altering pathways of energy metabolism. Immunoblotting was used to evaluate the regulation and post-transcriptional modifications of p53 in liver and skeletal muscle of red-eared slider turtles subjected to 5h or 20h of anoxic submergence. Tissue specific regulation of p53 was observed with the liver showing a more rapid activation of p53 in response to anoxia as well as differential expression of seven serine phosphorylation and two lysine acetylation sites when compared with skeletal muscle. Protein expression of MDM2, a major p53 inhibitor, was also examined but did not change during anoxia. Reverse-transcriptase PCR was used to assess transcript levels of selected p53 target genes (14-3-3σ, Gadd45α and Pgm) and one microRNA (miR-34a); results showed down-regulation of Pgm and up-regulation of the other three. These findings show an activation of p53 in response to anoxia exposure and suggest an important role for the p53 stress response pathway in regulating natural anoxia tolerance and hypometabolism in a vertebrate facultative anaerobe. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. NF-κB in The Mechanism of Brain Edema in Acute Liver Failure: Studies in Transgenic Mice

    Science.gov (United States)

    Jayakumar, A.R.; Bethea, J.R.; Tong, X.Y.; Gomez, J.; Norenberg, M.D.

    2014-01-01

    Astrocyte swelling and brain edema are major complications of the acute form of hepatic encephalopathy (acute liver failure, ALF). While elevated brain ammonia level is a well-known etiological factor in ALF, the mechanism by which ammonia brings about astrocyte swelling is not well understood. We recently found that astrocyte cultures exposed to ammonia activated nuclear factor-kappaB (NF-κB), and that pharmacological inhibition of such activation led to a reduction in astrocyte swelling. Although these findings suggest the involvement of NF-κB in astrocyte swelling in vitro, it is not known whether NF-κB contributes to the development of brain edema in ALF in vivo. Furthermore, pharmacological agents used to inhibit NF-κB may have non-specific effects. Accordingly, we used transgenic (Tg) mice that have a functional inactivation of astrocytic NF-κB and examined whether these mice are resistant to ALF-associated brain edema. ALF was induced in mice by treatment with the hepatotoxin thioacetamide (TAA). Wild type (WT) mice treated with TAA showed a significant increase in brain water content (1.65%) along with prominent astrocyte swelling and spongiosis of the neuropil, consistent with the presence of cytotoxic edema. These changes were not observed in Tg mice treated with TAA. Additionally, WT mice with ALF showed an increase in inducible nitric oxide synthase (iNOS) immunoreactivity in astrocytes from WT mice treated with TAA (iNOS is known to be activated by NF-κB and to contribute to cell swelling). By contrast, Tg mice treated with TAA did not exhibit brain edema, histological changes nor an increase in iNOS immunoreactivity. We also examined astrocytes cultures derived from Tg mice to determine whether these cells exhibit a lesser degree of swelling and cytopathological changes following exposure to ammonia. Astrocyte cultures derived from Tg mice showed no cell swelling nor morphological abnormalities when exposed to ammonia for 24 h. By contrast

  7. Treating fructose-induced metabolic changes in mice with high-intensity interval training: insights in the liver, white adipose tissue, and skeletal muscle.

    Science.gov (United States)

    Motta, Victor F; Bargut, Thereza L; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A

    2017-10-01

    Fructose-rich caloric sweeteners induce adverse changes in the metabolism of humans. The study evaluated the effects of high-intensity interval training (HIIT) on a fructose feeding model, focusing on the liver, white adipose tissue (WAT), skeletal muscle, and their interplay. Male C57BL/6 mice were fed for 18 wk one of the following diets: control (C; 5% of total energy from fructose) or fructose (F; 55% of total energy from fructose). In the 10th week, for an additional 8-wk period, the groups were divided into nontrained (NT) or HIIT groups, totaling four groups: C-NT, C-HIIT, F-NT, and F-HIIT. At the end of the experiment, fructose consumption in the F-NT group led to a high systolic blood pressure, high plasma triglycerides, insulin resistance with glucose intolerance, and lower insulin sensitivity. We also observed liver steatosis, adipocyte hypertrophy, and diminished gene expressions of peroxisome proliferator-activated receptor-γ coactivator 1-α and fibronectin type III domain containing 5 (FNDC5; irisin) in this F-NT group. These results were accompanied by decreased gene expressions of nuclear respiratory factor 1 and mitochondrial transcription factor A (markers of mitochondrial biogenesis), and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1 (markers of β-oxidation). HIIT improved all of these data in the C-HIIT and F-HIIT groups. In conclusion, in mice fed a fructose diet, HIIT improved body mass, blood pressure, glucose metabolism, and plasma triglycerides. Liver, WAT, and skeletal muscle were positively modulated by HIIT, indicating HIIT as a coadjutant treatment for diseases affecting these tissues. NEW & NOTEWORTHY We investigated the effects of high-intensity interval training (HIIT) in mice fed a fructose-rich diet and the resulting severe negative effect on the liver, white adipose tissue (WAT), and skeletal muscle, which reduced the expression of fibronectin type III domain containing 5 (FNDC5, irisin) and

  8. A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats

    Directory of Open Access Journals (Sweden)

    William W. French

    2017-06-01

    Full Text Available A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa and lean control (Fa/fa rats were randomly assigned to either a high-protein (40% energy or moderate-protein (20% energy diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8, lean 40% protein (L40; n = 10, obese 20% protein (O20; n = 8, and obese 40% protein (O40; n = 10. At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake (p < 0.05 compared to O20. O40 rats had lower liver weight (p < 0.05 compared to O20. However, O40 rats had higher orexin (p < 0.05 levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1 phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ mRNA expression compared to O20 (p < 0.05, with no difference in 5′ AMP-activated protein kinase (AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1, protein kinase B (Akt or p70 ribosomal S6 kinase (p70S6K phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

  9. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats

    DEFF Research Database (Denmark)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne

    2014-01-01

    , and aspartate and incorporation of (15)NH4(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation...... of (15)NH4(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH4(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined...

  10. Glucose Metabolic Changes in the Brain and Muscles of Patients with Nonspecific Neck Pain Treated by Spinal Manipulation Therapy: A [18F]FDG PET Study

    Directory of Open Access Journals (Sweden)

    Akie Inami

    2017-01-01

    Full Text Available Objective. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [18F]fluorodeoxyglucose ([18F]FDG PET. Methods. Twenty-one male volunteers were recruited for the present study. [18F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT intervention (treatment condition and once after resting (control condition. We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS activity, as well as muscle tension and subjective pain intensity in each subject. Results. Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity, and pain relief after SMT. Conclusion. Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.

  11. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    Science.gov (United States)

    Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

    2016-04-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

  12. Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry.

    Science.gov (United States)

    Sawada, Yoshikazu; Izumida, Yoshihiko; Takeuchi, Yoshinori; Aita, Yuichi; Wada, Nobuhiro; Li, EnXu; Murayama, Yuki; Piao, Xianying; Shikama, Akito; Masuda, Yukari; Nishi-Tatsumi, Makiko; Kubota, Midori; Sekiya, Motohiro; Matsuzaka, Takashi; Nakagawa, Yoshimi; Sugano, Yoko; Iwasaki, Hitoshi; Kobayashi, Kazuto; Yatoh, Shigeru; Suzuki, Hiroaki; Yagyu, Hiroaki; Kawakami, Yasushi; Kadowaki, Takashi; Shimano, Hitoshi; Yahagi, Naoya

    2017-11-04

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Reduced muscle activation during exercise related to brain oxygenation and metabolism in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nielsen, Jannie; Overgaard, M

    2010-01-01

    Maximal exercise may be limited by central fatigue defined as an inability of the central nervous system to fully recruit the involved muscles. This study evaluated whether a reduction in the cerebral oxygen-to-carbohydrate index (OCI) and in the cerebral mitochondrial oxygen tension relate to th...... indicating that reduced cerebral oxygenation may play a role in the development of central fatigue and may be an exercise capacity limiting factor.......Maximal exercise may be limited by central fatigue defined as an inability of the central nervous system to fully recruit the involved muscles. This study evaluated whether a reduction in the cerebral oxygen-to-carbohydrate index (OCI) and in the cerebral mitochondrial oxygen tension relate...... of perceived exertion (RPE), arm maximal voluntary force (MVC), and voluntary activation of elbow flexor muscles assessed with transcranial magnetic stimulation. Low intensity exercise did not produce any indication of central fatigue or marked cerebral metabolic deviations. Exercise in hypoxia (0.10) reduced...

  14. A correlation study of the expression of resistin and glycometabolism in muscle tissue after traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jin Peng; Zhu Lielie; Zhang Jiasheng; Xie Songling; Pan Da; Wen Hao; Meng Weiyang

    2014-01-01

    Objective:To investigate the expression pattern of resistin (RSTN) in skeletal muscle tissue and its influence on glycometabolism in rats with traumatic brain injury (TBI).Methods:Seventy-eight SD rats were randomly divided into traumatic group (n=36),RSTN group (n=36) and sham operation group (n=6).Fluid percussion TBI model was developed in traumatic and RSTN groups and the latter received additional 1 mg RSTN antibody treatment for each rat.At respectively 12 h,24 h,72 h,1 w,2 w,and 4 w after operation,venous blood was collected and the right hind leg skeletal muscle tissue was sampled.We used real-time PCR to determine mRNA expression of RSTN in skeletal muscles,western blot to determine RSTN protein expression and ELISA to assess serum insulin as well as fasting blood glucose (FBG) levels.Calculation of the quantitative insulin sensitivity check index (Q value) was also conducted.The above mentioned indicators and their correction were statistically analyzed.Results:Compared with sham operation group,the RSTN expression in the skeletal muscle as well as serum insulin and FBG levels revealed significant elevation (P<0.05),and reduced Q value (P<0.05) in traumatic group.Single factor linear correlation analysis showed a significant negative correlation between RSTN expression and Q values (P<0.001) in traumatic group.Conclusion:The expression of RSTN has been greatly increased in the muscular tissue of TBI rats and it was closely related to the index of glycometabolism.RSTN may play an important role in the process of insulin resistance after TBI.

  15. Genotoxicity of Styrene–Acrylonitrile Trimer in Brain, Liver, and Blood Cells of Weanling F344 Rats

    Science.gov (United States)

    Hobbs, Cheryl A.; Chhabra, Rajendra S.; Recio, Leslie; Streicker, Michael; Witt, Kristine L.

    2012-01-01

    Styrene–acrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P < 0.0001) in MN-RET were measured in both male and female rats administered SAN Trimer. The RET population was reduced in high dose male rats, suggesting chemical-related bone marrow toxicity. Results of the Comet assay showed significant, dose-related increases in DNA damage in brain cells of male (P < 0.0074) and female (P < 0.0001) rats; increased levels of DNA damage were also measured in liver cells and leukocytes of treated rats. Chemical-related cytotoxicity was not indicated in any of the tissues examined for DNA damage. The results of this subacute MN/Comet assay indicate induction of significant genetic damage in multiple tissues of weanling F344 male and female rats after oral exposure to SAN Trimer. PMID:22351108

  16. Adenosinetriphosphate content and adenosinetriphosphatase activity in cell fractions of the liver and brain of chick embryos and birds treated with gamma-rays

    International Nuclear Information System (INIS)

    Todorov, B.

    1977-01-01

    Studies are conducted on the level of ADP and the adenosinetriphosphatase in nuclei, mitochondria, and microsomes taken from the brain and liver of singly gamma-irradiated (1000 rd) chick embryos and birds. As a result of the treatment the ADP content dropped, while the activity of ADP rose. These changes were more strongly expressed in the nuclei, than in the mitochondria, and to a lesser extent - in the microsomes. Twelve-day chick embryos showed more markedly expressed radiosensitivity than newly hatched chicks. This embryonal stage is characterized by intense growth, differentiation and metabolic processes in the liver, which substantiate not only the higher radiosensitivity of this age group but the more strongly expressed changes in the liver as compared with the brain. (author)

  17. Effects of Replacement of Fishmeal with other Alternative Plant Sources in the Feed on Proximate Composition of Muscle, Liver and Ovary in Tilapia (Oreochromis nioloticus

    Directory of Open Access Journals (Sweden)

    Khalid Al-Ghanim

    2017-08-01

    Full Text Available ABSTRACT The major objective of this experiment was to assess the effect of alternate plant protein sources as a replacement for fish meal in feed on the proximate composition of muscle, liver and tissue in Oreochromis niloticus. O. niloticus of average size (average Weight 45.00±1.25 g, total length 13.28±1.42 cm were stocked in 100 L glass aquarium. Fish were fed with three experimental feeds (A, B and C and reference commercial feed (D for 16 weeks. Feed A, B and C was prepared from four different plant sources and fish meal (40 % crude protein. Fish were fed at the rate 3 % of body weight daily. It has been observed that tilapia fed with feed B in which 20 % fish meal was replaced compared to feed C with other plant sources of protein, had shown significantly higher total protein in their muscle compared to diet other experimental and commercial feeds. In O. niloticus minimum lipid content was recorded in fish fed with diet B compared to A, C and commercial feed. It has been concluded that 20-40% level of fish meal can be replaced in the diet of fish without having any impact on growth and chemical composition of muscle.

  18. Sarcopenia Impairs Prognosis of Patients with Hepatocellular Carcinoma: The Role of Liver Functional Reserve and Tumor-Related Factors in Loss of Skeletal Muscle Volume.

    Science.gov (United States)

    Imai, Kenji; Takai, Koji; Watanabe, Satoshi; Hanai, Tatsunori; Suetsugu, Atsushi; Shiraki, Makoto; Shimizu, Masahito

    2017-09-22

    Sarcopenia impairs survival in patients with hepatocellular carcinoma (HCC). This study aimed to clarify the factors that contribute to decreased skeletal muscle volume in patients with HCC. The third lumbar vertebra skeletal muscle index (L3 SMI) in 351 consecutive patients with HCC was calculated to identify sarcopenia. Sarcopenia was defined as an L3 SMI value ≤ 29.0 cm²/m² for women and ≤ 36.0 cm²/m² for men. The factors affecting L3 SMI were analyzed by multiple linear regression analysis and tree-based models. Of the 351 HCC patients, 33 were diagnosed as having sarcopenia and showed poor prognosis compared with non-sarcopenia patients ( p = 0.007). However, this significant difference disappeared after the adjustments for age, sex, Child-Pugh score, maximum tumor size, tumor number, and the degree of portal vein invasion by propensity score matching analysis. Multiple linear regression analysis showed that age ( p = 0.015) and sex ( p < 0.0001) were significantly correlated with a decrease in L3 SMI. Tree-based models revealed that sex (female) is the most significant factor that affects L3 SMI. In male patients, L3 SMI was decreased by aging, increased Child-Pugh score (≥56 years), and enlarged tumor size (<56 years). Maintaining liver functional reserve and early diagnosis and therapy for HCC are vital to prevent skeletal muscle depletion and improve the prognosis of patients with HCC.

  19. Hibernation impact on the catalytic activities of the mitochondrial D-3-hydroxybutyrate dehydrogenase in liver and brain tissues of jerboa (Jaculus orientalis

    Directory of Open Access Journals (Sweden)

    Hafiani Assia

    2003-09-01

    Full Text Available Abstract Background Jerboa (Jaculus orientalis is a deep hibernating rodent native to subdesert highlands. During hibernation, a high level of ketone bodies i.e. acetoacetate (AcAc and D-3-hydroxybutyrate (BOH are produced in liver, which are used in brain as energetic fuel. These compounds are bioconverted by mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH E.C. 1.1.1.30. Here we report, the function and the expression of BDH in terms of catalytic activities, kinetic parameters, levels of protein and mRNA in both tissues i.e brain and liver, in relation to the hibernating process. Results We found that: 1/ In euthemic jerboa the specific activity in liver is 2.4- and 6.4- fold higher than in brain, respectively for AcAc reduction and for BOH oxidation. The same differences were found in the hibernation state. 2/ In euthermic jerboa, the Michaelis constants, KM BOH and KM NAD+ are different in liver and in brain while KM AcAc, KM NADH and the dissociation constants, KD NAD+and KD NADH are similar. 3/ During prehibernating state, as compared to euthermic state, the liver BDH activity is reduced by half, while kinetic constants are strongly increased except KD NAD+. 4/ During hibernating state, BDH activity is significantly enhanced, moreover, kinetic constants (KM and KD are strongly modified as compared to the euthermic state; i.e. KD NAD+ in liver and KM AcAc in brain decrease 5 and 3 times respectively, while KD NADH in brain strongly increases up to 5.6 fold. 5/ Both protein content and mRNA level of BDH remain unchanged during the cold adaptation process. Conclusions These results cumulatively explained and are consistent with the existence of two BDH enzymatic forms in the liver and the brain. The apoenzyme would be subjected to differential conformational folding depending on the hibernation state. This regulation could be a result of either post-translational modifications and/or a modification of the mitochondrial membrane state

  20. Macro- and microelements in the rat liver, kidneys, and brain tissues; sex differences and effect of blood removal by perfusion in vivo.

    Science.gov (United States)

    Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan

    2017-03-01

    Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Eefsen, Martin; Hansen, Bent Adel

    2008-01-01

    Acute liver failure (ALF) is a condition with an unfavourable prognosis. Multiorgan failure and circulatory collapse are frequent causes of death, but cerebral edema and intracranial hypertension (ICH) are also common complications with a high risk of fatal outcome. The underlying pathogenesis has...... been extensively studied and although the development of cerebral edema and ICH is of a complex and multifactorial nature, it is well established that ammonia plays a pivotal role. This review will focus on the effects of hyperammonemia on neurotransmission, mitochondrial function, oxidative stress...

  2. Diet - liver disease

    Science.gov (United States)

    Proteins normally help the body repair tissue. They also prevent fatty buildup and damage to the liver cells. In people with badly damaged livers, proteins are not properly processed. Waste products may build up and affect the brain. Dietary ...

  3. Sparteine monooxygenase in brain and liver: Identified by the dopamine uptake blocker [3H]GBR-12935

    International Nuclear Information System (INIS)

    Kalow, W.; Tyndale, R.F.; Niznik, H.B.; Inaba, T.

    1990-01-01

    P450IID6 (human sparteine monooxygenase) metabolizes many drugs including neuroleptics, antidepressants, and beta-blockers. The P450IID6 exists in human, bovine, rat and canine brains, but in very low quantities causing methodological difficulties in its assessment. Work with [ 3 H]GBR-12935; 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenyl propyl) piperazine has shown that it binds a neuronal/hepatic protein with high affinity (∼7nM) and a rank order of inhibitory potency suggesting that the binding protein is cytochrome P450IID6. The binding was used to predict that d-amphetamine and methamphetamine would interact with P450IID6. Inhibition studies indicated that these compounds were competitive inhibitors of P450IID6. Haloperidol (HAL) and it's metabolite hydroxy-haloperidol (RHAL) are both competitive inhibitors of P450IID6 activity and were found to inhibit [ 3 H]GBR-12935 binding. K i values of twelve compounds (known to interact with the DA transporter or P450IID6) for [ 3 H]GRB-12935 binding and P450IID6 activity. The techniques are now available for measurements of cytochrome P450IID6 in healthy and diseased brain/liver tissue using radio-receptor binding assay techniques with [ 3 H]GBR-12935

  4. Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation.

    Science.gov (United States)

    Vargas, Hugo E; Laskus, Tomasz; Radkowski, Marek; Wilkinson, Jeff; Balan, Vijay; Douglas, David D; Harrison, M Edwyn; Mulligan, David C; Olden, Kevin; Adair, Debra; Rakela, Jorge

    2002-11-01

    Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5' untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated.

  5. Brain, kidney and liver 203Hg-methyl mercury uptake in the rat: Relationship to the neutral amino acid carrier

    International Nuclear Information System (INIS)

    Aschner, M.

    1989-01-01

    To investigate the effect of L-neutral amino acids on tissue levels of methyl mercury in the adult animal, rats were infused into the external jugular vein with solutions containing a) 0.05 mM 203 Hg-MeHgCl and saline, b) 0.05 mM 203 Hg-MgHgCl-0.1 mM L-cysteine, c) 0.05 mM 203 Hg-MeHgCl-0.1 mM L-cysteine-0.1 mM L-methionine, d) 0.05 mM 203 Hg-MeHgCl-0.1 mM L-leucine, or e) 0.05 mM 203 Hg-MeHgCl-0.1 mM L-cysteine-0.1 mM L-leucine. Groups of animals were sacrificed at 3 min. 7 hr, and 96 hr. Brain, kidney, and liver 203 Hg radioactivity was measured by means of gamma-scintillation spectrometry. Brain 203 Hg concentrations L-cysteine treated animals were significantly higher compared with saline treated animals (P 203 Hg uptake (P 203 Hg concentrations were not significantly different in any of the treatment groups compared with controls, irrespective of the sacrifice time. Furthermore, the percentage of diffusible 203 Hg (non-protein bound) at each sacrifice time was not statistically different irrespective of the treatment assigned. These results suggest that methyl mercury L-cysteine conjugates in the plasma may share a common transport step with the L-neutral amino acid carrier transport system and indicate the presence in brain capillaries of a transport system capable of selectively mediating methyl mercury uptake across the capillary endothelial cell membrane. (author)

  6. Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels

    DEFF Research Database (Denmark)

    Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik

    2016-01-01

    In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels...... in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P creatine for improved bioenergetics in energy-demanding tissues....

  7. Levels of metals in kidney, liver and muscle tissue and their relation to the occurrence of parasites in the red fox in the Lower Silesian Forest in Europe.

    Science.gov (United States)

    Binkowski, Łukasz J; Merta, Dorota; Przystupińska, Anna; Sołtysiak, Zenon; Pacoń, Jarosław; Stawarz, Robert

    2016-04-01

    Together with the occurrence of parasites, increased concentrations of xenobiotics, to which scavengers are greatly exposed, may significantly influence the physiology of red foxes. It is also suspected that these two factors interact. The accumulation of various metals (Ca, Cd, Cu, Fe, Hg, K, Mg, Ni, Pb, Zn) in kidney, liver and muscle tissue was investigated, as well as the occurrence of parasites, and the potential link to the presence of metals. Generally speaking, neither sex nor age influenced these concentrations. K, Mg and Fe were found in the highest concentrations and Hg was found in the lowest. Various relationships between the concentrations of metals were observed in the tissues. 34% of the specimens studied were hosts to parasites. No clear, significant connection between the concentrations and the occurrence of parasites was noted, but the discernible trend confirmed by the logistic regression, needs further study. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

    Science.gov (United States)

    Mathieu, Cécile; Li de la Sierra-Gallay, Ines; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-08-26

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Forms of n-3 (ALA, C18:3n-3 or DHA, C22:6n-3) Fatty Acids Affect Carcass Yield, Blood Lipids, Muscle n-3 Fatty Acids and Liver Gene Expression in Lambs.

    Science.gov (United States)

    Ponnampalam, Eric N; Lewandowski, Paul A; Fahri, Fahri T; Burnett, Viv F; Dunshea, Frank R; Plozza, Tim; Jacobs, Joe L

    2015-11-01

    The effects of supplementing diets with n-3 alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on plasma metabolites, carcass yield, muscle n-3 fatty acids and liver messenger RNA (mRNA) in lambs were investigated. Lambs (n = 120) were stratified to 12 groups based on body weight (35 ± 3.1 kg), and within groups randomly allocated to four dietary treatments: basal diet (BAS), BAS with 10.7 % flaxseed supplement (Flax), BAS with 1.8 % algae supplement (DHA), BAS with Flax and DHA (FlaxDHA). Lambs were fed for 56 days. Blood samples were collected on day 0 and day 56, and plasma analysed for insulin and lipids. Lambs were slaughtered, and carcass traits measured. At 30 min and 24 h, liver and muscle samples, respectively, were collected for determination of mRNA (FADS1, FADS2, CPT1A, ACOX1) and fatty acid composition. Lambs fed Flax had higher plasma triacylglycerol, body weight, body fat and carcass yield compared with the BAS group (P DHA supplementation increased carcass yield and muscle DHA while lowering plasma insulin compared with the BAS diet (P DHA treatment increased (P DHA concentration. Liver mRNA FADS2 was higher and CPT1A lower in the DHA group (P DHA diet. In summary, supplementation with ALA or DHA modulated plasma metabolites, muscle DHA, body fat and liver gene expression differently.

  10. The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial

    NARCIS (Netherlands)

    Blanco-Rojo, R.; Alcala-Diaz, J.F.; Wopereis, S.; Perez-Martinez, P.; Quintana-Navarro, G.M.; Marin, C.; Ordovas, J.M.; Ommen, B. van; Perez-Jimenez, F.; Delgado-Lista, J.; Lopez-Miranda, J.

    2016-01-01

    Aims/hypothesis: The aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function. Methods: The study was performed in 642

  11. Transient gestational exposure to drinking water containing excess hexavalent chromium modifies insulin signaling in liver and skeletal muscle of rat progeny.

    Science.gov (United States)

    Shobana, Navaneethabalakrishnan; Aruldhas, Mariajoseph Michael; Tochhawng, Lalmuankimi; Loganathan, Ayyalu; Balaji, Sadhasivam; Kumar, Mani Kathiresh; Banu, Liaquat Alikhan Sheerin; Navin, Ajit Kumar; Mayilvanan, Chinnaiyan; Ilangovan, Ramachandran; Balasubramanian, Karundevi

    2017-11-01

    Chromium (Cr), an essential micronutrient potentiates insulin action, whereas excess hexavalent Cr (CrVI) acts as an endocrine disruptor. Pregnant mothers living in areas abutting industries using the metal and chromite ore dumps are exposed to ground water contaminated with Cr. Nevertheless, the impact of prenatal exposure to excess CrVI on insulin signaling in the progeny remains obscure. We tested the hypothesis "transient gestational exposure to drinking water containing excess CrVI may modify insulin signaling during postnatal life". Pregnant Wistar rats were given drinking water containing 50, 100 and 200 ppm CrVI (K 2 Cr 2 O 7 ) from gestational day 9-14 encompassing the period of organogenesis; the male progenies were tested at postnatal day 60. Neither fasting blood glucose nor oral glucose tolerance was altered in CrVI treated progeny. Nevertheless, western blot detection pointed out attenuated expression level of insulin receptor (IR), its downstream signaling molecules (IRS-1, pIRS-1 Tyr632 , Akt and pAkt Ser473 ) and organ specific glucose transporters (GLUT2 in liver and GLUT4 in gastrocnemius muscle), along with a significant increase in serum insulin level in male progenies exposed to CrVI. While 14 C-2-deoxy glucose uptake increased in the liver, the same decreased in the skeletal muscle whereas, 14 C-glucose oxidation recorded a consistent decrease in both tissues of CrVI exposed rats. These findings support our hypothesis and suggest that transient gestational exposure to excess CrVI may affect insulin signaling and glucose oxidation in the progeny, predictably rendering them vulnerable to insulin resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

    Directory of Open Access Journals (Sweden)

    Junhwan Kim

    2016-01-01

    Full Text Available Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  13. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    Science.gov (United States)

    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  14. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    DEFF Research Database (Denmark)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees,...

  15. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    Science.gov (United States)

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P brain, liver, and kidney (all P male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P female mice and in kidney (male and female mice) but decreased 55% in brain (P differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  16. The effect of the combined feed "Aller Aqua" on the content of free amino acids in the muscles and liver of brown (Salmo trutta Linnaeus, 1758 and rainbow (Oncorhynchus mykiss Walbaum, 1792 trout

    Directory of Open Access Journals (Sweden)

    L. Galoyan

    2017-12-01

    Full Text Available Purpose. To study the level of amino acid assimilation from the protein of the combined feed and also to characterize the amino acid composition of proteins in muscles and liver of the brown and rainbow trout in conditions of feeding them with the specialized production combined feed manufactured by Aller Aqua. Methodology. The total amino acid composition of muscle and liver tissues was determined by ion-exchange liquid column chromatography. Findings. The amino acid composition of the investigated feed as a whole corresponds to the spectrum of amino acids in the tissues of muscles and liver of the brown and rainbow trout. Both a significant predominance of glutamine and glutamic acid was detected in the liver and in the muscles of fish. Among the essential amino acids in the muscles and liver of the fish studied, the largest share belongs to leucine, arginine and lysine. Originality. First investigated the effect of artificial feeding with specialized productional fodder «Aller Aqua» on the amino acid composition of tissues of brown and rainbow trout reared in conditions of industrial aquaculture. Practical value. Currently, studies devoted to a comprehensive assessment of the effect of mixed feeds on growth and development, and in particular on the amino acid composition of salmon fish tissues, acquire particular attention. This work makes it possible to investigate the degree of assimilation of protein components of the artificial feed for rainbow trout and discuss the perspectives of the adjustment of the imbalance and deficiency of amino acid composition in the feed.

  17. Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type II and complex II-III deficiency in liver and muscle.

    Science.gov (United States)

    Wolfe, Lynne A; He, Miao; Vockley, Jerry; Payne, Nicole; Rhead, William; Hoppel, Charles; Spector, Elaine; Gernert, Kim; Gibson, K Michael

    2010-12-01

    We describe a 22-year-old male who developed severe hypoglycemia and lethargy during an acute illness at 4 months of age and subsequently grew and developed normally. At age 4 years he developed recurrent vomiting with mild hyperammonemia and dehydration requiring frequent hospitalizations. Glutaric aciduria Type II was suspected based upon biochemical findings and managed with cornstarch, carnitine and riboflavin supplements. He did not experience metabolic crises between ages 4-12 years. He experienced recurrent vomiting, mild hyperammonemia, and generalized weakness associated with acute illnesses and growth spurts. At age 18 years, he developed exercise intolerance and proximal muscle weakness leading to the identification of multiple acyl-CoA dehydrogenase and complex II/III deficiencies in both skeletal muscle and liver. Subsequent molecular characterization of the ETFDH gene revealed novel heterozygous mutations, p.G274X:c.820 G > T (exon 7) and p.P534L: c.1601 C > T (exon 12), the latter within the iron sulfur-cluster and predicted to affect ubiquinone reductase activity of ETFDH and the docking of ETF to ETFDH. Our case supports the concept of a structural interaction between ETFDH and other enzyme partners, and suggests that the conformational change upon ETF binding to ETFDH may play a key role in linking ETFDH to II/III super-complex formation.

  18. The psoas muscle transversal diameter predicts mortality in patients with cirrhosis on a waiting list for liver transplantation: A retrospective cohort study.

    Science.gov (United States)

    Huguet, Audrey; Latournerie, Marianne; Debry, Pauline Houssel; Jezequel, Caroline; Legros, Ludivine; Rayar, Michel; Boudjema, Karim; Guyader, Dominique; Jacquet, Edouard Bardou; Thibault, Ronan

    2018-02-09

    Malnutrition impairs prognosis in liver cirrhosis. Our aims were to determine (1) if transversal (TPTI) and axial (APTI) psoas thickness indices predict mortality in cirrhotic patients and (2) the feasibility and reproducibility of transversal (TDPM) and axial (ADPM) diameters of the psoas muscle measurements. This was a retrospective study. Inclusion criteria included cirrhosis diagnosis, on liver transplantation waiting list, and abdominal computed tomography (CT) scan within the 3 mo preceding list inscription. TDPM and ADPM were measured on a single umbilicus-targeted CT image by non-expert and expert operators. TPTI or APTI (mm/m) were calculated as TDPM or ADPM/height (m). Area under the receiver operating characteristic curve (AUC) and Cox proportional hazard models were assessed. TPTI and APTI interobserver agreement: κ correlation test. A total of 173 patients were included. Low TPTI was associated with increased mortality: AUC = 0.66 (95% confidence interval, 0.51-0.80). TPTI was the only factor associated with mortality (hazard ratio = 0.87, 95% confidence interval 0.76-0.99, P = 0.034). There was an almost perfect interobserver agreement between the two operators: TDPM, κ = 0.97; ADPM, κ = 0.94; P <0.0001. TPTI measured on umbilicus-targeted CT scan before inscription on the waiting list for liver transplantation predicts mortality of cirrhotic patients. TPTI measurement is easy and reliable, even by a non-trained operator, and this is highly feasible in daily clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Survival prediction using temporal muscle thickness measurements on cranial magnetic resonance images in patients with newly diagnosed brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Furtner, Julia; Prayer, Daniela [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Berghoff, Anna S.; Zielinski, Christoph C.; Preusser, Matthias [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Albtoush, Omar M. [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); University of Jordan, Department of Radiology and Nuclear Medicine, Amman (Jordan); Woitek, Ramona; Asenbaum, Ulrika [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Widhalm, Georg; Gatterbauer, Brigitte [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, Karin [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Birner, Peter [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Medical University of Vienna, Department of Pathology, Vienna (Austria); Aretin, Bernadette [General Hospital Vienna, Pharmacy Department, Vienna (Austria); Bartsch, Rupert [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Schoepf, Veronika [University of Graz, Institute of Psychology, Graz (Austria); BioTechMed, Graz (Austria)

    2017-08-15

    To evaluate the prognostic relevance of temporal muscle thickness (TMT) in brain metastasis patients. We retrospectively analysed TMT on magnetic resonance (MR) images at diagnosis of brain metastasis in two independent cohorts of 188 breast cancer (BC) and 247 non-small cell lung cancer (NSCLC) patients (overall: 435 patients). Survival analysis using a Cox regression model showed a reduced risk of death by 19% with every additional millimetre of baseline TMT in the BC cohort and by 24% in the NSCLC cohort. Multivariate analysis included TMT and diagnosis-specific graded prognostic assessment (DS-GPA) as covariates in the BC cohort (TMT: HR 0.791/CI [0.703-0.889]/p < 0.001; DS-GPA: HR 1.433/CI [1.160-1.771]/p = 0.001), and TMT, gender and DS-GPA in the NSCLC cohort (TMT: HR 0.710/CI [0.646-0.780]/p < 0.001; gender: HR 0.516/CI [0.387-0.687]/p < 0.001; DS-GPA: HR 1.205/CI [1.018-1.426]/p = 0.030). TMT is easily and reproducibly assessable on routine MR images and is an independent predictor of survival in patients with newly diagnosed brain metastasis from BC and NSCLC. TMT may help to better define frail patient populations and thus facilitate patient selection for therapeutic measures or clinical trials. Further prospective studies are needed to correlate TMT with other clinical frailty parameters of patients. (orig.)

  20. Survival prediction using temporal muscle thickness measurements on cranial magnetic resonance images in patients with newly diagnosed brain metastases

    International Nuclear Information System (INIS)

    Furtner, Julia; Prayer, Daniela; Berghoff, Anna S.; Zielinski, Christoph C.; Preusser, Matthias; Albtoush, Omar M.; Woitek, Ramona; Asenbaum, Ulrika; Widhalm, Georg; Gatterbauer, Brigitte; Dieckmann, Karin; Birner, Peter; Aretin, Bernadette; Bartsch, Rupert; Schoepf, Veronika

    2017-01-01

    To evaluate the prognostic relevance of temporal muscle thickness (TMT) in brain metastasis patients. We retrospectively analysed TMT on magnetic resonance (MR) images at diagnosis of brain metastasis in two independent cohorts of 188 breast cancer (BC) and 247 non-small cell lung cancer (NSCLC) patients (overall: 435 patients). Survival analysis using a Cox regression model showed a reduced risk of death by 19% with every additional millimetre of baseline TMT in the BC cohort and by 24% in the NSCLC cohort. Multivariate analysis included TMT and diagnosis-specific graded prognostic assessment (DS-GPA) as covariates in the BC cohort (TMT: HR 0.791/CI [0.703-0.889]/p < 0.001; DS-GPA: HR 1.433/CI [1.160-1.771]/p = 0.001), and TMT, gender and DS-GPA in the NSCLC cohort (TMT: HR 0.710/CI [0.646-0.780]/p < 0.001; gender: HR 0.516/CI [0.387-0.687]/p < 0.001; DS-GPA: HR 1.205/CI [1.018-1.426]/p = 0.030). TMT is easily and reproducibly assessable on routine MR images and is an independent predictor of survival in patients with newly diagnosed brain metastasis from BC and NSCLC. TMT may help to better define frail patient populations and thus facilitate patient selection for therapeutic measures or clinical trials. Further prospective studies are needed to correlate TMT with other clinical frailty parameters of patients. (orig.)

  1. A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats.

    Science.gov (United States)

    French, William W; Dridi, Sami; Shouse, Stephanie A; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I

    2017-06-08

    A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake ( p diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 ( p protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

  2. Further statistical analysis for genome-wide expression evolution in primate brain/liver/fibroblast tissue

    Directory of Open Access Journals (Sweden)

    Gu Jianying

    2004-05-01

    Full Text Available Abstract In spite of only a 1-2 per cent genomic DNA sequence difference, humans and chimpanzees differ considerably in behaviour and cognition. Affymetrix microarray technology provides a novel approach to addressing a long-term debate on whether the difference between humans and chimpanzees results from the alteration of gene expressions. Here, we used several statistical methods (distance method, two-sample t-tests, regularised t-tests, ANOVA and bootstrapping to detect the differential expression pattern between humans and great apes. Our analysis shows that the pattern we observed before is robust against various statistical methods; that is, the pronounced expression changes occurred on the human lineage after the split from chimpanzees, and that the dramatic brain expression alterations in humans may be mainly driven by a set of genes with increased expression (up-regulated rather than decreased expression (down-regulated.

  3. Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo

    Directory of Open Access Journals (Sweden)

    Brian C. Jensen

    2017-06-01

    Full Text Available Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR, whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR and platelet-derived growth factor receptor (PDGFR.TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities. Cardiotoxicity is very rare in patients treated with erlotinib, but considerably more common after sunitinib treatment. We hypothesized that the deleterious effects of TKIs on the heart were related to their impact on cardiac metabolism. Methods: Female FVB/N mice (10/group were treated with therapeutic doses of sunitinib (40 mg/kg, erlotinib (50 mg/kg, or vehicle daily for two weeks. Echocardiographic assessment of the heart in vivo was performed at baseline and on Day 14. Heart, skeletal muscle, liver and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Results: Compared to vehicle-treated controls, sunitinib-treated mice had significant decreases in systolic function, whereas erlotinib-treated mice did not. Non-targeted metabolomics analysis of heart identified significant decreases in docosahexaenoic acid (DHA, arachidonic acid (AA/ eicosapentaenoic acid (EPA, O-phosphocolamine, and 6-hydroxynicotinic acid after sunitinib treatment. DHA was significantly decreased in skeletal muscle (quadriceps femoris, while elevated cholesterol was identified in liver and elevated ethanolamine identified in serum. In contrast, erlotinib affected only one metabolite (spermidine significantly increased. Conclusions: Mice treated with sunitinib exhibited systolic dysfunction within two weeks, with significantly lower heart and skeletal muscle

  4. Metabolic fingerprints of serum, brain, and liver are distinct for mice with cerebral and noncerebral malaria: a ¹H NMR spectroscopy-based metabonomic study.

    Science.gov (United States)

    Ghosh, Soumita; Sengupta, Arjun; Sharma, Shobhona; Sonawat, Haripalsingh M

    2012-10-05

    Cerebral malaria (CM) is a life-threatening disease in humans caused by Plasmodium falciparum, leading to high mortality. Plasmodium berghei ANKA (PbA) infection in C57Bl/6 mice induces pathologic symptoms similar to that in human CM. However, experimental CM incidence in mice is variable, and there are no known metabolic correlates/fingerprints for the animals that develop CM. Here, we have used (1)H NMR-based metabonomics to investigate the metabolic changes in the mice with CM with respect to the mice that have noncerebral malaria (NCM) of the same batchmates with identical genetic backgrounds and infected simultaneously. The metabolic profile of the infected mice (both CM and NCM) was separately compared with the metabolite profile of uninfected control mice of same genetic background. The objective of this study was to search for metabolic changes/fingerprints of CM and identify the pathways that might be differentially altered in mice that succumbed to CM. The results show that brain, liver, and sera exhibit unique metabolic fingerprints for CM over NCM mice. Some of the major fingerprints are increased level of triglycerides, VLDL-cholesterol in sera of CM mice, and decreased levels of glutamine in the sera concomitant with increased levels of glutamine in the brain of the mice with CM. Moreover, glycerophosphocholine is decreased in both the brain and the liver of animals with CM, and myo-inositol and histamine are increased in the liver of CM mice. The metabolic fingerprints in brain, sera, and liver of mice with CM point toward perturbation in the ammonia detoxification pathway and perturbation in lipid and choline metabolism in CM specifically. The study helps us to understand the severity of CM over NCM and in unrevealing the specific metabolic pathways that are compromised in CM.

  5. Chronic Opium Treatment Can Differentially Induce Brain and Liver Cells Apoptosis in Diabetic and Non-diabetic Male and Female Rats

    OpenAIRE

    Asiabanha, Majid; Asadikaram, Gholamreza; Rahnema, Amir; Mahmoodi, Mehdi; Hasanshahi, Gholamhosein; Hashemi, Mohammad; Khaksari, Mohammad

    2011-01-01

    It has been shown that some opium derivatives promote cell death via apoptosis. This study was designed to examine the influence of opium addiction on brain and liver cells apoptosis in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium-addicted, diabetic and diabetic opium-addicted male and female rats. Apoptosis was evaluated by TUNEL and DNA fragmentation assays. Results of this study showed that apoptosis in opium-addicted and dia...

  6. Feeding during the resting phase causes profound changes in physiology and desynchronization between liver and muscle rhythms of rats

    NARCIS (Netherlands)

    Opperhuizen, Anne-Loes; Wang, Dawei; Foppen, E.; Jansen, Remi; Boudzovitch-Surovtseva, Olga; de Vries, Janneke; Fliers, Eric; Kalsbeek, A.

    2016-01-01

    Shiftworkers run an increased risk of developing metabolic disorders, presumably as a result of disturbed circadian physiology. Eating at a time-of-day that is normally dedicated to resting and fasting, may contribute to this association. The hypothalamus is the key brain area that integrates

  7. A combination of ascorbic acid and α-tocopherol or a combination of Mg and Zn are both able to reduce the adverse effects of lindane-poisoning on rat brain and liver.

    Science.gov (United States)

    Hfaiedh, Najla; Murat, Jean-Claude; Elfeki, Abdelfettah

    2012-10-01

    The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of supplementation with ascorbic acid (Vit C) and α-tocopherol (Vit E) or with Mg and Zn upon lindane-induced damages in liver and brain. Under our experimental conditions, lindane poisoning (5mg/kg body weight per day for 3 days) resulted in (1) an increased level of plasma glucose, cholesterol and triglycerides, (2) an increased activity of LDH, ALP, AST, ALT, (3) an oxidative stress in liver and brain as revealed by an increased level of lipids peroxidation (TBARS) and a decrease of glutathione-peroxidase, superoxide dismutase and catalase activities in liver and brain. In conclusion, both Vit C+E or Mg+Zn treatments display beneficial effects upon oxidative stress induced by lindane treatment in liver and brain. Copyright © 2012 Elsevier GmbH. All rights reserved.

  8. Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

    Science.gov (United States)

    Ragy, Merhan Mamdouh

    2015-01-01

    Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

  9. CD11c-positive cells from brain, spleen, lung, and liver exhibit site-specific immune phenotypes and plastically adapt to new environments.

    Science.gov (United States)

    Immig, Kerstin; Gericke, Martin; Menzel, Franziska; Merz, Felicitas; Krueger, Martin; Schiefenhövel, Fridtjof; Lösche, Andreas; Jäger, Kathrin; Hanisch, Uwe-Karsten; Biber, Knut; Bechmann, Ingo

    2015-04-01

    The brain's immune privilege has been also attributed to the lack of dendritic cells (DC) within its parenchyma and the adjacent meninges, an assumption, which implies maintenance of antigens rather than their presentation in lymphoid organs. Using mice transcribing the green fluorescent protein under the promoter of the DC marker CD11c (itgax), we identified a juxtavascular population of cells expressing this DC marker and demonstrated their origin from bone marrow and local microglia. We now phenotypically compared this population with CD11c/CD45 double-positive cells from lung, liver, and spleen in healthy mice using seven-color flow cytometry. We identified unique, site-specific expression patterns of F4/80, CD80, CD86, CX3CR1, CCR2, FLT3, CD103, and MHC-II. Furthermore, we observed the two known CD45-positive populations (CD45(high) and CD45(int) ) in the brain, whereas liver, lung, and spleen exhibited a homogeneous CD45(high) population. CD11c-positive microglia lacked MHC-II expression and CD45(high) /CD11c-positive cells from the brain have a lower percentage of MHC-II-positive cells. To test whether phenotypical differences are fixed by origin or specifically develop due to environmental factors, we transplanted brain and spleen mononuclear cells on organotypic slice cultures from brain (OHSC) and spleen (OSSC). We demonstrate that adaption and ramification of MHC-II-positive splenocytes is paralleled by down-regulation of MHC-II, whereas brain-derived mononuclear cells neither ramified nor up-regulated MHC-II in OSSCs. Thus, brain-derived mononuclear cells maintain their MHC-II-negative phenotype within the environment of an immune organ. Intraparenchymal CD11c-positive cells share immunophenotypical characteristics of DCs from other organs but remain unique for their low MHC-II expression. © 2014 Wiley Periodicals, Inc.

  10. Simultaneous infusion of glutamine and branched-chain amino acids (BCAA) to septic rats does not have more favorable effect on protein synthesis in muscle, liver, and small intestine than separate infusions.

    Science.gov (United States)

    Holecek, Milan; Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek

    2006-01-01

    Glutamine and branched-chain amino acids (BCAA; valine, leucine, and isoleucine) are used as nutrition supplements in the treatment of proteocatabolic illness. We hypothesized that simultaneous administration of BCAA and glutamine affects protein metabolism more significantly than separate administration. In the present study, we evaluated their effect on protein synthesis in skeletal muscle, liver, and jejunum of septic rats. Twenty-four hours after induction of sepsis by subcutaneous injection of turpentine, the rats were infused for 6 hours with 5 mL of 1.75% glutamine, 1.75% BCAA, 1.75% glutamine+BCAA, or saline solution. The control group consisted of intact rats infused with saline. Protein synthesis was measured at the end of infusion by a "flooding method" with [3,4,5-(3)H]phenylalanine. In turpentine-treated animals, we observed a decrease in glutamine concentration in blood plasma and skeletal muscle, a decrease in BCAA concentration in liver and jejunum, and a decrease in protein synthesis in all tissues. Glutamine or glutamine+BCAA infusion increased glutamine concentration in plasma and muscle and stimulated protein synthesis in the liver. The BCAA infusion enhanced concentrations of BCAA in plasma and tissues, but the effect of BCAA on protein synthesis was insignificant. Synergistic effect of simultaneous infusion of glutamine and BCAA on protein synthesis was not observed. We conclude that glutamine infusion to rats with septic injury may significantly improve impaired protein synthesis in the liver and that there is no synergistic effect of glutamine and BCAA infusion on protein synthesis in skeletal muscle, liver, and jejunum.

  11. Minimal hepatic encephalopathy in children with liver cirrhosis: diffusion-weighted MR imaging and proton MR spectroscopy of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Abdel Razek, Ahmed Abdel Khalek; Ezzat, Amany [Mansoura University Hospital, Department of Diagnostic Radiology, Mansoura Faculty of Medicine, Mansoura (Egypt); Abdalla, Ahmed; Megahed, Ahmed; Barakat, Tarek [Mansoura Children Hospital, Gastroenterology and Hepatology Unit, Mansoura Faculty of Medicine, Mansoura (Egypt)

    2014-10-15

    The aim of this work was to detect minimal hepatic encephalopathy (minHE) in children with diffusion-weighted MR imaging (DWI) and proton magnetic resonance spectroscopy ({sup 1}H-MRS) of the brain. Prospective study conducted upon 30 consecutive children (age range 6-16 years, 21 boys and 9 girls) with liver cirrhosis and 15 age- and sex-matched healthy control children. Patients with minHE (n = 17) and with no minHE (n = 13) groups and control group underwent DWI, {sup 1}H-MRS, and neuropsychological tests (NPTs). The glutamate or glutamine (Glx), myoinositol (mI), choline (Cho), and creatine (Cr) at the right ganglionic region were determined at {sup 1}H-MRS. The apparent diffusion coefficient (ADC) value and metabolic ratios of Glx/Cr, mI/Cr, and Cho/Cr were calculated. There was elevated ADC value and Glx/Cr and decreased mI/CI and Ch/Cr in patients with minHE compared to no minHE and control group. There was significant difference between minHE, no minHE, and control group in the ADC value (P = 0.001 for all groups), GLx/Cr (P = 0.001 for all groups), mI/Cr (P = 0.004, 0.001, and 0.001, respectively), Ch/Cr (P = 0.001 for all groups), and full-scale IQ of NPT (P = 0.001, 0.001, and 0.143, respectively). The NPT of minHE had negative correlation with ADC value (r = -0.872, P = 0.001) and GLx/Cr (r = -0.812, P = 0.001) and positive correlation with mI/Cr (r = 0.732, P = 0.001). DWI and {sup 1}H-MRS are imaging modalities that can detect minHE in children with liver cirrhosis and correlate well with parameters of NPT. (orig.)

  12. Minimal hepatic encephalopathy in children with liver cirrhosis: diffusion-weighted MR imaging and proton MR spectroscopy of the brain

    International Nuclear Information System (INIS)

    Abdel Razek, Ahmed Abdel Khalek; Ezzat, Amany; Abdalla, Ahmed; Megahed, Ahmed; Barakat, Tarek

    2014-01-01

    The aim of this work was to detect minimal hepatic encephalopathy (minHE) in children with diffusion-weighted MR imaging (DWI) and proton magnetic resonance spectroscopy ( 1 H-MRS) of the brain. Prospective study conducted upon 30 consecutive children (age range 6-16 years, 21 boys and 9 girls) with liver cirrhosis and 15 age- and sex-matched healthy control children. Patients with minHE (n = 17) and with no minHE (n = 13) groups and control group underwent DWI, 1 H-MRS, and neuropsychological tests (NPTs). The glutamate or glutamine (Glx), myoinositol (mI), choline (Cho), and creatine (Cr) at the right ganglionic region were determined at 1 H-MRS. The apparent diffusion coefficient (ADC) value and metabolic ratios of Glx/Cr, mI/Cr, and Cho/Cr were calculated. There was elevated ADC value and Glx/Cr and decreased mI/CI and Ch/Cr in patients with minHE compared to no minHE and control group. There was significant difference between minHE, no minHE, and control group in the ADC value (P = 0.001 for all groups), GLx/Cr (P = 0.001 for all groups), mI/Cr (P = 0.004, 0.001, and 0.001, respectively), Ch/Cr (P = 0.001 for all groups), and full-scale IQ of NPT (P = 0.001, 0.001, and 0.143, respectively). The NPT of minHE had negative correlation with ADC value (r = -0.872, P = 0.001) and GLx/Cr (r = -0.812, P = 0.001) and positive correlation with mI/Cr (r = 0.732, P = 0.001). DWI and 1 H-MRS are imaging modalities that can detect minHE in children with liver cirrhosis and correlate well with parameters of NPT. (orig.)

  13. Percutaneous Needle Tenotomy for the Treatment of Muscle and Tendon Contractures in Adults With Brain Damage: Results and Complications.

    Science.gov (United States)

    Coroian, Flavia; Jourdan, Claire; Froger, Jérome; Anquetil, Claire; Choquet, Olivier; Coulet, Bertand; Laffont, Isabelle

    2017-05-01

    To study the results and complications of percutaneous needle tenotomy for superficial retracted tendons in patients with brain damage. Prospective observational study. University hospital. Patients with severe brain damage (N=38; mean age, 60.7y; age range, 24-93y; 21 women) requiring surgical management of contractures and eligible for percutaneous needle tenotomy were enrolled between February 2015 and February 2016. The percutaneous needle tenotomy gesture was performed by a physical medicine and rehabilitation physician trained by an orthopedic surgeon, under local or locoregional anesthesia. Treated tendons varied among patients. All patients were evaluated at 1, 3, and 6 months to assess surgical outcomes (joint range of motion [ROM], pain, and functional improvement) while screening for complications. Improvements in ROM (37/38) and contractures-related pain (12/12) were satisfactory. Functional results were satisfactory (Goal Attainment Scale score ≥0) for most patients (37/38): nursing (n=12), putting shoes on (n=8), getting in bed or sitting on a chair (n=6), verticalization (n=7), transfers and gait (n=8), and grip (n=2). Five patients had complications related to the surgical gesture: cast-related complications (n=2), hand hematoma (n=2), and cutaneous necrosis of the Achilles tendon in a patient with previous obliterative arteriopathy of the lower limbs (n=1). Percutaneous needle tenotomy yields good results in the management of selected superficial muscle and tendon contractures. The complications rate is very low, and this treatment can be an alternative to conventional surgery in frail patients with neurologic diseases. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  14. Protective effect of Allium sativum (garlic) aqueous extract against lead-induced oxidative stress in the rat brain, liver, and kidney.

    Science.gov (United States)

    Manoj Kumar, V; Henley, A K; Nelson, C J; Indumati, O; Prabhakara Rao, Y; Rajanna, S; Rajanna, B

    2017-01-01

    The present investigation was undertaken to evaluate the ameliorative activity of Allium sativum against lead-induced oxidative stress in the brain, liver, and kidney of male rats. Four groups of male Wistar strain rats (100-120 g) were taken: group 1 received 1000 mg/L sodium acetate and group 2 was given 1000 mg/L lead acetate through drinking water for 2 weeks. Group 3 and 4 were treated with 250 mg/kg body weight/day of A. sativum and 500 mg/kg body weight/day of A. sativum, respectively, by oral intubation for a period of 2 weeks along with lead acetate. The rats were sacrificed after treatment and the brain, liver, and kidney were isolated on ice. In the brain, four important regions namely the hippocampus, cerebellum, cerebral cortex, and brain stem were separated and used for the present investigation. Blood was also drawn by cardiac puncture and preserved in heparinized vials at 4 °C for estimation of delta-aminolevulinic acid dehydratase (ALAD) activity. The results showed a significant (p sativum resulted in tissue-specific recovery of oxidative stress parameters namely ROS, LPP, and TPCC. A. sativum treatment also restored the blood delta-ALAD activity back to control. Overall, our results indicate that A. sativum administration could be an effective antioxidant treatment strategy for lead-induced oxidative insult.

  15. Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents*

    Science.gov (United States)

    Zhou, Yun; Holmseth, Silvia; Guo, Caiying; Hassel, Bjørnar; Höfner, Georg; Huitfeldt, Henrik S.; Wanner, Klaus T.; Danbolt, Niels C.

    2012-01-01

    The GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed in relation to their potential roles in controlling the action of transmitter GABA in the nervous system. We have generated the first mice lacking the GAT2 (slc6a13) gene. Deletion of GAT2 (both mRNA and protein) neither affected growth, fertility, nor life span under nonchallenging rearing conditions. Immunocytochemistry showed that the GAT2 protein was predominantly expressed in the plasma membranes of periportal hepatocytes and in the basolateral membranes of proximal tubules in the renal cortex. This was validated by processing tissue from wild-type and knockout mice in parallel. Deletion of GAT2 reduced liver taurine levels by 50%, without affecting the expression of the taurine transporter TAUT. These results suggest an important role for GAT2 in taurine uptake from portal blood into liver. In support of this notion, GAT2-transfected HEK293 cells transported [3H]taurine. Furthermore, most of the uptake of [3H]GABA by cultured rat hepatocytes was due to GAT2, and this uptake was inhibited by taurine. GAT2 was not detected in brain parenchyma proper, excluding a role in GABA inactivation. It was, however, expressed in the leptomeninges and in a subpopulation of brain blood vessels. Deletion of GAT2 increased brain taurine levels by 20%, suggesting a taurine-exporting role for GAT2 in the brain. PMID:22896705

  16. Comparison of (31)P saturation and inversion magnetization transfer in human liver and skeletal muscle using a clinical MR system and surface coils.

    Science.gov (United States)

    Buehler, Tania; Kreis, Roland; Boesch, Chris

    2015-02-01

    (31)P MRS magnetization transfer ((31)P-MT) experiments allow the estimation of exchange rates of biochemical reactions, such as the creatine kinase equilibrium and adenosine triphosphate (ATP) synthesis. Although various (31)P-MT methods have been successfully used on isolated organs or animals, their application on humans in clinical scanners poses specific challenges. This study compared two major (31)P-MT methods on a clinical MR system using heteronuclear surface coils. Although saturation transfer (ST) is the most commonly used (31)P-MT method, sequences such as inversion transfer (IT) with short pulses might be better suited for the specific hardware and software limitations of a clinical scanner. In addition, small NMR-undetectable metabolite pools can transfer MT to NMR-visible pools during long saturation pulses, which is prevented with short pulses. (31)P-MT sequences were adapted for limited pulse length, for heteronuclear transmit-receive surface coils with inhomogeneous B1 , for the need for volume selection and for the inherently low signal-to-noise ratio (SNR) on a clinical 3-T MR system. The ST and IT sequences were applied to skeletal muscle and liver in 10 healthy volunteers. Monte-Carlo simulations were used to evaluate the behavior of the IT measurements with increasing imperfections. In skeletal muscle of the thigh, ATP synthesis resulted in forward reaction constants (k) of 0.074 ± 0.022 s(-1) (ST) and 0.137 ± 0.042 s(-1) (IT), whereas the creatine kinase reaction yielded 0.459 ± 0.089 s(-1) (IT). In the liver, ATP synthesis resulted in k = 0.267 ± 0.106 s(-1) (ST), whereas the IT experiment yielded no consistent results. ST results were close to literature values; however, the IT results were either much larger than the corresponding ST values and/or were widely scattered. To summarize, ST and IT experiments can both be implemented on a clinical body scanner with heteronuclear transmit-receive surface coils; however, ST results are

  17. GCN2 in the Brain Programs PPARγ2 and Triglyceride Storage in the Liver during Perinatal Development in Response to Maternal Dietary Fat

    Science.gov (United States)

    Xu, Xu; Hu, Jingjie; McGrath, Barbara C.; Cavener, Douglas R.

    2013-01-01

    The liver plays a central role in regulating lipid metabolism and facilitates efficient lipid utilization and storage. We discovered that a modest increase in maternal dietary fat in mice programs triglyceride storage in the liver of their developing offspring. The activation of this programming is not apparent, however, until several months later at the adult stage. We found that the perinatal programming of adult hepatic triglyceride storage was controlled by the eIF2α kinase GCN2 (EIF2AK4) in the brain of the offspring, which stimulates epigenetic modification of the Pparγ2 gene in the neonatal liver. Genetic ablation of Gcn2 in the offspring exhibited reduced hepatic triglyceride storage and repressed expression of the peroxisome proliferator-activated receptor gamma 2 (Pparγ2) and two lipid droplet protein genes, Fsp27 and Cidea. Brain-specific, but not liver-specific, Gcn2 KO mice exhibit these same defects demonstrating that GCN2 in the developing brain programs hepatic triglyceride storage. GCN2 and nutrition-dependent programming of Pparγ2 is correlated with trimethylation of lysine 4 of histone 3 (H3K4me3) in the Pparγ2 promoter region during neonatal development. In addition to regulating hepatic triglyceride in response to modest changes in dietary fat, Gcn2 deficiency profoundly impacts the severity of the obese-diabetic phenotype of the leptin receptor mutant (db/db) mouse, by reducing hepatic steatosis and obesity but exacerbating the diabetic phenotype. We suggest that GCN2-dependent perinatal programming of hepatic triglyceride storage is an adaptation to couple early nutrition to anticipated needs for hepatic triglyceride storage in adults. However, increasing the hepatic triglyceride set point during perinatal development may predispose individuals to hepatosteatosis, while reducing circulating fatty acid levels that promote insulin resistance. PMID:24130751

  18. Characterization of basal gene expression trends over a diurnal cycle in Xiphophorus maculatus skin, brain and liver.

    Science.gov (United States)

    Lu, Yuan; Reyes, Jose; Walter, Sean; Gonzalez, Trevor; Medrano, Geraldo; Boswell, Mikki; Boswell, William; Savage, Markita; Walter, Ronald

    2018-06-01

    Evolutionarily conserved diurnal circadian mechanisms maintain oscillating patterns of gene expression based on the day-night cycle. Xiphophorus fish have been used to evaluate transcriptional responses after exposure to various light sources and it was determined that each source incites distinct genetic responses in skin tissue. However, basal expression levels of genes that show oscillating expression patterns in day-night cycle, may affect the outcomes of such experiments, since basal gene expression levels at each point in the circadian path may influence the profile of identified light responsive genes. Lack of knowledge regarding diurnal fluctuations in basal gene expression patterns may confound the understanding of genetic responses to external stimuli (e.g., light) since the dynamic nature of gene expression implies animals subjected to stimuli at different times may be at very different stages within the continuum of genetic homeostasis. We assessed basal gene expression changes over a 24-hour period in 200 select Xiphophorus gene targets known to transcriptionally respond to various types of light exposure. We identified 22 genes in skin, 36 genes in brain and 28 genes in liver that exhibit basal oscillation of expression patterns. These genes, including known circadian regulators, produced the expected expression patterns over a 24-hour cycle when compared to circadian regulatory genes identified in other species, especially human and other vertebrate animal models. Our results suggest the regulatory network governing diurnal oscillating gene expression is similar between Xiphophorus and other vertebrates for the three Xiphophorus organs tested. In addition, we were able to categorize light responsive gene sets in Xiphophorus that do, and do not, exhibit circadian based oscillating expression patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Rate equation for creatine kinase predicts the in vivo reaction velocity: 31P NMR surface coil studies in brain, heart, and skeletal muscle of the living rat

    International Nuclear Information System (INIS)

    Bittl, J.A.; DeLayre, J.; Ingwall, J.S.

    1987-01-01

    Brain, heart, and skeletal muscle contain four different creatine kinase isozymes and various concentrations of substrates for the creatine kinase reaction. To identify if the velocity of the creatine kinase reaction under cellular conditions is regulated by enzyme activity and substrate concentrations as predicted by the rate equation, the authors used 31 P NMR and spectrophotometric techniques to measure reaction velocity, enzyme content, isozyme distribution, and concentrations of substrates in brain, heart, and skeletal muscle of living rat under basal or resting conditions. The total tissue activity of creatine kinase in the direction of MgATP synthesis provided an estimate for V/sub max/ and exceeded the NMR-determined in vivo reaction velocities by an order of magnitude. The isozyme composition varied among the three tissues: >99% BB for brain; 14% MB, 61% MM, and 25% mitochondrial for heart; and 98% MM and 2% mitochondrial for skeletal muscle. The NMR-determined reaction velocities agreed with predicted values from the creatine kinase rate equation. The concentrations of free creatine and cytosolic MgADP, being less than or equal to the dissociation constants for each isozyme, were dominant terms in the creatine kinase rate equation for predicting the in vivo reaction velocity. Thus, they observed that the velocity of the creatine kinase reaction is regulated by total tissue enzyme activity and by the concentrations of creatine and MgADP in a manner that is independent of isozyme distribution

  20. The role of PGC-1alpha on mitochondrial function and apoptotic susceptibility in muscle

    DEFF Research Database (Denmark)

    Adhihetty, Peter J; Uguccioni, Giulia; Leick, Lotte

    2009-01-01

    Mitochondria are critical for cellular bioenergetics, and they mediate apoptosis within cells. We used whole body peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) knockout (KO) animals to investigate its role on organelle function, apoptotic signaling, and cytochrome......-c oxidase activity, an indicator of mitochondrial content, in muscle and other tissues (brain, liver, and pancreas). Lack of PGC-1alpha reduced mitochondrial content in all muscles (17-44%; P liver, and pancreas. However, the tissue expression of proteins involved...

  1. Characterization of the chicken muscle insulin receptor

    International Nuclear Information System (INIS)

    Adamo, M.; Simon, J.; Rosebrough, R.W.; McMurtry, J.P.; Steele, N.C.; LeRoith, D.

    1987-01-01

    Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125 I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125 I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125 I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens

  2. Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble[(3,5,5-Trimethylhexanoyl)ferrocene

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan

    2007-01-01

    Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (......, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.......Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl......)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of a- and ¿-tocopherols and glutathione (GSH) were also higher. In contrast, the brain...

  3. The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors.

    Directory of Open Access Journals (Sweden)

    Jin Xu

    Full Text Available The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD. The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD, we aimed to understand how ischemia/reperfusion (I/R injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration.Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13 and DBD (n = 10 livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22 and DBD (n = 13 livers.When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05 and C22 ceramide (p<0.05 were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST of DCD allografts had significantly increased.These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation.

  4. Temperature and metal exposure affect membrane fatty acid composition and transcription of desaturases and elongases in fathead minnow muscle and brain.

    Science.gov (United States)

    Fadhlaoui, Mariem; Pierron, Fabien; Couture, Patrice

    2018-02-01

    In this study, we tested the hypothesis that metal exposure affected the normal thermal response of cell membrane FA composition and of elongase and desaturase gene transcription levels. To this end, muscle and brain membrane FA composition and FA desaturase (fads2, degs2 and scd2) and elongase (elovl2, elovl5 and elovl6) gene transcription levels were analyzed in fathead minnows (Pimephales promelas) acclimated for eight weeks to 15, 25 or 30°C exposed or not to cadmium (Cd, 6μg/l) or nickel (Ni, 450 6μg/l). The response of membrane FA composition to temperature variations or metal exposure differed between muscle and brain. In muscle, an increase of temperature induced a decrease of polyunsaturated FA (PUFA) and an increase of saturated FA (SFA) in agreement with the current paradigm. Although a similar response was observed in brain between 15 and 25°C, at 30°C, brain membrane unsaturation was higher than predicted. In both tissues, metal exposure affected the normal thermal response of membrane FA composition. The transcription of desaturases and elongases was higher in the brain and varied with acclimation temperature and metal exposure but these variations did not generally reflect changes in membrane FA composition. The mismatch between gene transcription and membrane composition highlights that several levels of control other than gene transcription are involved in adjusting membrane FA composition, including post-transcriptional regulation of elongases and desaturases and de novo phospholipid biosynthesis. Our study also reveals that metal exposure affects the mechanisms involved in adjusting cell membrane FA composition in ectotherms. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. [Simultaneous determination of 7 arsenic species in chicken muscle and chicken liver with high performance liquid chromatography-inductively coupled plasma mass spectrometry].

    Science.gov (United States)

    Yang, Lijun; Hu, Qiaoru; Guo, Wei; Liu, Yumin; Song, Xiaohua; Zhang, Pengcheng

    2011-05-01

    A method for the simultaneous determination of 7 arsenic species was developed with high performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The sample was extracted with artificial gastric juice. The HPLC separation was performed on an anion analytical column utilizing a gradient elution program of ammonium carbonate and water as the mobile phase. Identification and quantification were achieved by ICP-MS. Good linearities of 7 arsenic species were observed in the range from 1 microg/kg to 50 microg/kg with the correlation coefficients greater than 0.999. The average recoveries of 7 arsenic species spiked at the three levels of 1, 2 and 10 microg/kg ranged from 84.3% to 106.6% with the relative standard deviations of 1.4%-4.2%. The quantification limits of 7 arsenic species were 1 microg/kg. The method was proved to be good reproducibility, high sensitivity and simple preprocessing. This method is suitable for the simultaneous determination of 7 arsenic species in chicken muscle and chicken liver.

  6. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  7. Mössbauer study of exogenous iron redistribution between the brain and the liver after administration of {sup 57}Fe{sub 3}O{sub 4} ferrofluid in the ventricle of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Polikarpov, Dmitry, E-mail: polikarpov.imp@gmail.com [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Russian National Research Medical University named after N.I.Pirogov, Moscow (Russian Federation); Gabbasov, Raul; Cherepanov, Valery [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Loginova, Natalia; Loseva, Elena [Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow (Russian Federation); Nikitin, Maxim [Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow (Russian Federation); Yurenia, Anton; Panchenko, Vladislav [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Lomonosov Moscow State University, Moscow (Russian Federation)

    2015-04-15

    Iron clearance pathways after the injection of {sup 57}Fe{sub 3}O{sub 4}-based ferrofluid into the brain ventricles were studied histologically and by Mössbauer spectroscopy. It was found that the dextran coated initial nanobeads of the ferrofluid disintegrated in the brain into separate superparamagnetic nanoparticles within a week after the injection. The exogenous iron completely exited all ventricular cavities of the brain within a week after the injection but remained in the white matter for months. Kupffer cells with the exogenous iron appeared in the rat liver 2 hours after the injection. Their concentration reached its maximum on the third day and dropped to zero within a week. The exogenous iron appeared in the spleen a week after the injection and remained in the spleen for months.

  8. MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation

    Directory of Open Access Journals (Sweden)

    McKiernan Patrick J

    2011-05-01

    Full Text Available Abstract Background Propionic acidaemia (PA results from deficiency of Propionyl CoA carboxylase, the commonest form presenting in the neonatal period. Despite best current management, PA is associated with severe neurological sequelae, in particular movement disorders resulting from basal ganglia infarction, although the pathogenesis remains poorly understood. The role of liver transplantation remains controversial but may confer some neuro-protection. The present study utilises quantitative magnetic resonance spectroscopy (MRS to investigate brain metabolite alterations in propionic acidaemia during metabolic stability and acute encephalopathic episodes. Methods Quantitative MRS was used to evaluate brain metabolites in eight children with neonatal onset propionic acidaemia, with six elective studies acquired during metabolic stability and five studies during acute encephalopathic episodes. MRS studies were acquired concurrently with clinically indicated MR imaging studies at 1.5 Tesla. LCModel software was used to provide metabolite quantification. Comparison was made with a dataset of MRS metabolite concentrations from a cohort of children with normal appearing MR imaging. Results MRI findings confirm the vulnerability of basal ganglia to infarction during acute encephalopathy. We identified statistically significant decreases in basal ganglia glutamate+glutamine and N-Acetylaspartate, and increase in lactate, during encephalopathic episodes. In white matter lactate was significantly elevated but other metabolites not significantly altered. Metabolite data from two children who had received liver transplantation were not significantly different from the comparator group. Conclusions The metabolite alterations seen in propionic acidaemia in the basal ganglia during acute encephalopathy reflect loss of viable neurons, and a switch to anaerobic respiration. The decrease in glutamine + glutamate supports the hypothesis that they are consumed to

  9. Muscle contractures in patients with cerebral palsy and acquired brain injury are associated with extracellular matrix expansion, pro-inflammatory gene expression, and reduced rRNA synthesis.

    Science.gov (United States)

    von Walden, Ferdinand; Gantelius, Stefan; Liu, Chang; Borgström, Hanna; Björk, Lars; Gremark, Ola; Stål, Per; Nader, Gustavo A; Pontén, Eva

    2018-03-23

    Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested. The biceps muscles of children and adolescents with CP/ABI (n=20) and typically developing controls (n=10) were investigated. We used immunohistochemistry, qRT-PCR and western blotting to assess gene expression relevant to growth and size homeostasis. Classical pro-inflammatory cytokines and genes involved in extracellular matrix production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase (POL) I transcription factors, 45s pre-rRNA and 28S rRNA. The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures; possibly underlying stunted growth and perimysial extracellular matrix expansion. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  10. Effects of hepatic ischemia-reperfusion injury on the P-glycoprotein activity at the liver canalicular membrane and blood-brain barrier determined by in vivo administration of rhodamine 123 in rats.

    Science.gov (United States)

    Miah, Mohammad K; Shaik, Imam H; Bickel, Ulrich; Mehvar, Reza

    2014-04-01

    To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood-brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker. Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis. P-gp protein levels at the liver canalicular membrane were increased by twofold after 24 h of reperfusion. However, the biliary excretion of RH-123 was reduced in these rats by 26%, presumably due to IR-induced reductions in the liver uptake of the marker and hepatic ATP concentrations. At the BBB, a 24% overexpression of P-gp in the 24-h IR animals was associated with a 30% decrease in the apparent brain uptake clearance of RH-123. The pharmacokinetics or brain distribution of RH-123 was not affected by the 12-h IR injury. Hepatic IR injury may alter the peripheral pharmacokinetics and brain distribution of drugs that are transported by P-gp and possibly other transporters.

  11. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

    Science.gov (United States)

    Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

    2015-08-01

    To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

  12. Ameliorating reactive oxygen species-induced in vitro lipid peroxidation in brain, liver, mitochondria and DNA damage by Zingiber officinale Roscoe.

    Science.gov (United States)

    Ajith, T A

    2010-01-01

    Iron is an essential nutrient for a number of cellular activities. However, excess cellular iron can be toxic by producing reactive oxygen species (ROS) such as superoxide anion (O(2) (-)) and hydroxyl radical (HO(·)) that damage proteins, lipids and DNA. Mutagenic and genotoxic end products of lipid peroxidation can induce the decline of mitochondrial respiration and are associated with various human ailments including aging, neurodegenerative disorders, cancer etc. Zingiber officinale Roscoe (ginger) is a widely used spice around the world. The protective effect of aqueous ethanol extract of Z. officinale against ROS-induced in vitro lipid peroxidation and DNA damage was evaluated in this study. The lipid peroxidation was induced by hydroxyl radical generated from Fenton's reaction in rat liver and brain homogenates and mitochondrial fraction (isolated from rat liver). The DNA protection was evaluated using H(2)O(2)-induced changes in pBR-322 plasmid and Fenton reaction-induced DNA fragmentation in rat liver. The results indicated that Z. officinale significantly (Pofficinale in the liver homogenate was 94 %. However, the extract could partially alleviate the DNA damage. The protective mechanism can be correlated to the radical scavenging property of Z. officinale. The results of the study suggest the possible nutraceutical role of Z. officinale against the oxidative stress induced human ailments.

  13. Dietary Omega-3 Fatty Acid Deficiency and High Fructose Intake in the Development of Metabolic Syndrome, Brain Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos

    2013-07-01

    Full Text Available Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS. Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD, promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health.

  14. Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

    Science.gov (United States)

    Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

    2012-11-30

    Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Oxidative stress response of Forster's terns (Sterna forsteri) and Caspian terns (Hydroprogne caspia) to mercury and selenium bioaccumulation in liver, kidney, and brain

    Science.gov (United States)

    Hoffman, David J.; Eagles-Smith, Collin A.; Ackerman, Joshua T.; Adelsbach, Terrence L.; Stebbins, Katherine R.

    2011-01-01

    Bioindicators of oxidative stress were examined in prebreeding and breeding adult and chick Forster's terns (Sterna forsteri) and in prebreeding adult Caspian terns (Hydroprogne caspia) in San Francisco Bay, California. Highest total mercury (THg) concentrations (mean±standard error;μg/g dry wt) in liver (17.7±1.7), kidney (20.5±1.9), and brain (3.0±0.3) occurred in breeding adult Forster's terns. The THg concentrations in liver were significantly correlated with hepatic depletion of reduced glutathione (GSH), increased oxidized glutathione (GSSG):GSH ratio, and decreased hepatic gamma-glutamyl transferase (GGT) activity in adults of both tern species. Prefledging Forster's tern chicks with one-fourth the hepatic THg concentration of breeding adults exhibited effects similar to adults. Total mercury-related renal GSSG increased in adults and chicks. In brains of prebreeding adults, THg was correlated with a small increase in glucose-6-phosphate dehydrogenase (G-6-PDH) activity, suggestive of a compensatory response. Brain THg concentrations were highest in breeding adult Forster's terns and brain tissue exhibited increased lipid peroxidation as thiobarbituric acid-reactive substances, loss of protein bound thiols (PBSH), and decreased activity of antioxidant enzymes, GSSG reductase (GSSGrd), and G-6-PDH. In brains of Forster's tern chicks there was a decrease in total reduced thiols and PBSH. Multiple indicator responses also pointed to greater oxidative stress in breeding Forster's terns relative to prebreeding terns, attributable to the physiological stress of reproduction. Some biondicators also were related to age and species, including thiol concentrations. Enzymes GGT, G-6-PDH, and GSSGred activities were related to species. Our results indicate that THg concentrations induced oxidative stress in terns, and suggest that histopathological, immunological, and behavioral effects may occur in terns as reported in other species.

  16. Effect of. gamma. radiation in relatively low dose on the activity of glutaminase in subcellular fraction of brain and liver cells. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Tkach, V M

    1973-01-01

    The effect of ..gamma..-irradiation at a dose of 40 rads was studied on the exchange of glutamine in rats. It has been shown that the irradiation leads to a significant lowering of the activity of glutaminamidohydrolase (I) in brain mitochondria and in the liver after 1, 3, 7, 15, and 30 days post exposure. In the fractions containing nuclei, fraction of myofibrillae and connective tissue, a slow down of the deamidation of glutamine also takes place, and only after 7 days the ammonium separation from glutamine increases and returns to normal. At the 15 and 30 days a second wave of the lower rate of the activity of I takes place. The type of the changes of I is the same in both organs, but in the liver it is expressed to a lesser degree. (JPRS)

  17. Adding exercise training to rosuvastatin treatment: influence on serum lipids and biomarkers of muscle and liver damage.

    Science.gov (United States)

    Coen, Paul M; Flynn, Michael G; Markofski, Melissa M; Pence, Brandt D; Hannemann, Robert E

    2009-07-01

    Statin treatment and exercise training can improve lipid profile when administered separately. The efficacy of exercise and statin treatment combined, and its impact on myalgia and serum creatine kinase (CK) have not been completely addressed. The purpose of this study was to determine the effect of statin treatment and the addition of exercise training on lipid profile, including oxidized low-density lipoprotein (oxLDL), and levels of CK and alanine transaminase. Thirty-one hypercholesterolemic and physically inactive subjects were randomly assigned to rosuvastatin (R) or rosuvastatin/exercise (RE) group. A third group of physically active hypercholesterolemic subjects served as an active control group (AC). The R and RE groups received rosuvastatin treatment (10 mg/d) for 20 weeks. From week 10 to week 20, the RE group also participated in a combined endurance and resistive exercise training program (3 d/wk). Lipid profile was determined for all subjects at week 0 (Pre), week 10 (Mid), and week 20 (Post). The CK and alanine transaminase levels were measured at the same time points in the RE and R groups and 48 hours after the first and fifth exercise bout in the RE group. Each RE subject was formally queried about muscle fatigue, soreness, and stiffness before each training session. Total, LDL, and oxLDL cholesterol was lower in the RE and R groups at Mid and Post time points when compared with Pre. Oxidized LDL was lower in the RE group compared with the R group at the Post time point. When treatment groups (R and RE) were combined, high-density lipoprotein levels were increased and triglycerides decreased across time. Creatine kinase increased in the RE group 48 hours after the first exercise bout, but returned to baseline levels 48 hours after the fifth exercise bout. Rosuvastatin treatment decreased total, LDL, and oxLDL cholesterol. The addition of an exercise training program resulted in a further decrease in oxLDL. There was no abnormal sustained increase

  18. The Muscle Sensor for on-site neuroscience lectures to pave the way for a better understanding of brain-machine-interface research.

    Science.gov (United States)

    Koizumi, Amane; Nagata, Osamu; Togawa, Morio; Sazi, Toshiyuki

    2014-01-01

    Neuroscience is an expanding field of science to investigate enigmas of brain and human body function. However, the majority of the public have never had the chance to learn the basics of neuroscience and new knowledge from advanced neuroscience research through hands-on experience. Here, we report that we produced the Muscle Sensor, a simplified electromyography, to promote educational understanding in neuroscience. The Muscle Sensor can detect myoelectric potentials which are filtered and processed as 3-V pulse signals to shine a light bulb and emit beep sounds. With this educational tool, we delivered "On-Site Neuroscience Lectures" in Japanese junior-high schools to facilitate hands-on experience of neuroscientific electrophysiology and to connect their text-book knowledge to advanced neuroscience researches. On-site neuroscience lectures with the Muscle Sensor pave the way for a better understanding of the basics of neuroscience and the latest topics such as how brain-machine-interface technology could help patients with disabilities such as spinal cord injuries. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Molecular assembly and biosynthesis of acetylcholinesterase in brain and muscle: The roles of t-peptide, FHB domain and N-linked glycosylation

    Directory of Open Access Journals (Sweden)

    Vicky P. Chen

    2011-10-01

    Full Text Available Acetylcholinesterase (AChE is responsible for the hydrolysis of the neurotransmitter, acetylcholine, in the nervous system. The functional localization and oligomerization of AChE T variant are depending primarily on the association of their anchoring partners, either collagen tail (ColQ or proline rich membrane anchor (PRiMA. Complexes with ColQ represent the asymmetric forms (A12 in muscle, while complexes with PRiMA represent tetrameric globular forms (G4 mainly found in brain and muscle. Apart from these traditional molecular forms, a ColQ-linked asymmetric form and a PRiMA-linked globular form of hybrid cholinesterases (ChEs, having both AChE and BChE catalytic subunits, were revealed in chicken brain and muscle. The similarity of various molecular forms of AChE and BChE raises interesting question regarding to their possible relationship in enzyme assembly and localization. The focus of this review is to provide current findings about the biosynthesis of different forms of ChEs together with their anchoring proteins.

  20. Distribution of 14C-morphine and macromolecules in the brain and liver and their nuclei in pregnant rats and their foetuses after infusion of morphine into pregnant rats at near-term

    International Nuclear Information System (INIS)

    Steele, W.J.; Johannesson, T.

    1975-01-01

    Timed-pregnant (day 21 or 22) Sprague-Dawley rats were administered 14 C-morphine (2.85 mci/mmol) 5 mg/kg/hr, or saline in equivalent volumes, by continuous intravenous infusion for periods of up to 4hrs. The brains and livers of the maternal rats and of their foetuses were collected and their nuclei were isolated. The tissues and nuclei isolated from them were analyzed for DNA, RNA, protein content and radioactivity. Morphine infused maternal rats exhibited no significant difference in the total amount of DNA, RNA and protein in the brain or in the concentration of these constituents in brain nuclei. The concentration of nuclear RNA in foetal brain of morphine infused mothers was significantly lower at 4 hrs than that of saline infused controls. It was concluded that RNA synthesis in the foetal brain must be much more sensitive to the inhibitory effect of morphine on macromolecular synthesis than that in maternal brain. The change in nuclear RNA concentration in foetal brain became significantly different when morphine reached its highest level in foetal brain nuclei. The morphine concentration (pmol 14 C-morphine equivalents per mg DNA) in the brain of foetal and maternal rats was the same at each time period, whereas the maternal liver levels were at least eight times greater than those in foetal liver. The concentrations in foetal brain nuclei were 2-14 times greater than those in maternal brain nuclei, whereas levels in the latter were found to be low and virtually constant at all time periods tested. It was concluded that foetal brain nuclei have a greater capacity to bind or retain morphine than maternal brain nuclei. (author)

  1. Distribution of /sup 14/C-morphine and macromolecules in the brain and liver and their nuclei in pregnant rats and their foetuses after infusion of morphine into pregnant rats at near-term

    Energy Technology Data Exchange (ETDEWEB)

    Steele, W J; Johannesson, T [Iowa Univ., Iowa City (USA)

    1975-01-01

    Timed-pregnant (day 21 or 22) Sprague-Dawley rats were administered /sup 14/C-morphine (2.85 mci/mmol) 5 mg/kg/hr, or saline in equivalent volumes, by continuous intravenous infusion for periods of up to 4hrs. The brains and livers of the maternal rats and of their foetuses were collected and their nuclei were isolated. The tissues and nuclei isolated from them were analyzed for DNA, RNA, protein content and radioactivity. Morphine infused maternal rats exhibited no significant difference in the total amount of DNA, RNA and protein in the brain or in the concentration of these constituents in brain nuclei. The concentration of nuclear RNA in foetal brain of morphine infused mothers was significantly lower at 4 hrs than that of saline infused controls. It was concluded that RNA synthesis in the foetal brain must be much more sensitive to the inhibitory effect of morphine on macromolecular synthesis than that in maternal brain. The change in nuclear RNA concentration in foetal brain became significantly different when morphine reached its highest level in foetal brain nuclei. The morphine concentration (pmol /sup 14/C-morphine equivalents per mg DNA) in the brain of foetal and maternal rats was the same at each time period, whereas the maternal liver levels were at least eight times greater than those in foetal liver. The concentrations in foetal brain nuclei were 2-14 times greater than those in maternal brain nuclei, whereas levels in the latter were found to be low and virtually constant at all time periods tested. It was concluded that foetal brain nuclei have a greater capacity to bind or retain morphine than maternal brain nuclei.

  2. Effects of Tianmagouteng particles on brain cognitive function in spontaneously hypertensive rats with hyperactivity of liver-yang: A [F-18] FDG micro-PET imaging study.

    Science.gov (United States)

    Zhang, Xiu-Jing; Sun, Tian-Cai; Liu, Zi-Wang; Wang, Feng-Jiao; Wang, Yong-De; Liu, Jing

    2017-11-01

    To collect visualized proof of Tianmagouteng particles (TMGTP) in alleviating cognitive dysfunction and to explore its effects on brain activity in spontaneously hypertensive rats (SHRs) with hyperactivity of liver-yang (Gan Yang Shang Kang, GYSK). Sixteen SHRs were randomized into treatment group and non-treatment. The SHR with GYSK was induced by gavaging aconite decoction (10mL/kg at 0.2g/mL). After the SHR models were prepared, the rats in the treatment group were administered TMGTP (10mL/kg) once a day for 14days.The rats in the non-treatment group or normal rats (control group) received an equivalent volume of saline. Morris water maze test was conducted before and after the treatment to observe cognitive function. Fluorine 18-deoxy glucose [F-18]FDG micro-PET brain imaging scans was performed after treatment. Data were analyzed with two-sample t-test (Pfunctions, TMGTP induced strong brain activity in the following sites: right dorsolateral nucleus and ventrolateral nucleus of thalamus, amygdala, left met thalamus, cerebellum leaflets, original crack, front cone crack, loop-shaped leaflets; but deactivation of right medial frontal gyrus, bilateral corpus callosum, hippocampus, and left dentate gyrus. TMGTP could alleviate cognitive dysfunction in SHRs with GYSK, which was possibly by inducing alteration of glucose metabolism in different brain regions with corresponding functions. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Clinical impact of preoperative brain MR angiography and MR imaging in candidates for liver transplantation: a propensity score-matching study in a single institution

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Mi Sun; Kim, Ho Sung; Jung, Seung Chai; Choi, Choong Gon; Kim, Sang Joon [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Song pa-gu, Seoul (Korea, Republic of); Lim, Young-Suk [University of Ulsan College of Medicine, Department of Gastroenterology, Seoul (Korea, Republic of); Jeon, Sang-Beom [University of Ulsan College of Medicine, Department of Neurology, Seoul (Korea, Republic of); Kim, Seon-Ok [University of Ulsan College of Medicine, Department of Clinical Epidemiology and Biostatistics, Seoul (Korea, Republic of); Kim, Hwa Jung [University of Ulsan College of Medicine, Department of Preventive Medicine, Seoul (Korea, Republic of); Hwang, Shin [University of Ulsan College of Medicine, Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Seoul (Korea, Republic of)

    2017-08-15

    To investigate the prevalence of cerebrovascular stenosis and white matter lesions on preoperative magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI) in liver transplantation candidates. This retrospective study included 1,460 consecutive patients with liver cirrhosis (LC) who underwent MRA with/without brain MRI for pretransplantation evaluation. These patients were matched with 5,331 controls using propensity scores, and the prevalences of significant cerebrovascular stenosis and white matter lesions were compared. A matched analysis of 1,264 pairs demonstrated that the prevalence of significant stenosis was comparable between LC patients and controls (2.2% vs. 1.4%, P = 0.143). LC and most of LC-related parameters were not associated with stenosis. Significant white matter lesions were more common in LC patients (2.8% vs. 1.3%, P = 0.036). A high Model for End-Stage Liver Disease (MELD) score (OR 1.11, CI 1.03-1.20, P = 0.008, for infarction; OR 1.1, CI 1.04-1.16, P = 0.001, for haemorrhage) and stroke history (OR 179.06, CI 45.19-709.45, P < 0.001) were predictors of perioperative stroke. LC patients and control subjects demonstrated similar cerebrovascular stenosis prevalences, whereas white matter lesions were more common in LC patients. A high MELD score and stroke history contribute as predictors of perioperative stroke. (orig.)

  4. Histopathological Study of Protective Effects of Honey on Subacute Toxicity of Acrylamide-Induced Tissue Lesions in Rats’ Brain and Liver

    Directory of Open Access Journals (Sweden)

    Parichehr Ahrari Roodi

    2018-04-01

    Full Text Available Background: The therapeutic potential of honey is related to antioxidant activity against reactive oxygen species because it contains compounds such as polyphenols; therefore, we evaluated the potential protective effect of honey on subacute toxicity of ACR by histopathologic study on tissue lesions in rat. Methods: In Ferdowsi University of Mashhad, Mashhad, Iran, 2016, male Wistar rats were divided into 7 groups. To induce toxicity, ACR was injected (50 mg/kg for 11 d to rats in 5 groups. In treatment groups, rats received three doses of honey 1.25, 2.5, and 5 g/kg in addition to the ACR. The two remaining groups received vitamin E (200 IU/kg and normal saline as positive and negative control respectively. On the last day, after necropsy, tissue specimens from brain and liver were collected for histopathological studies. Results: Receiving of ACR caused tissue injuries including degeneration, necrosis, hyperemia, hemorrhage and inflammation in liver; ischemic cell change, hyperemia, hemorrhage and edema in brain tissue. Administration of honey considerably reduced tissue damages caused by ACR, particularly with dosage 5 g/kg. Conclusion: The severity of tissue lesions caused by the ACR can be reduced by honey, likely through its antioxidant activity. Increasing concentrations of honey will enhance its effectiveness.

  5. Sun-drying diminishes the antioxidative potentials of leaves of Eugenia uniflora against formation of thiobarbituric acid reactive substances induced in homogenates of rat brain and liver.

    Science.gov (United States)

    Kade, Ige Joseph; Ibukun, Emmanuel Oluwafemi; Nogueira, Cristina Wayne; da Rocha, Joao Batista Teixeira

    2008-08-01

    Extracts from leaves of Pitanga cherry (Eugenia uniflora) are considered to be effective against many diseases, and are therefore used in popular traditional medicines. In the present study, the antioxidative effect of sun-dried (PCS) and air-dried (PCA) ethanolic extracts of Pitanga cherry leaves were investigated. The antioxidant effects were tested by measuring the ability of both PCS and PCA to inhibit the formation of thiobarbituric acid reactive species (TBARS) induced by prooxidant agents such as iron (II) and sodium nitroprusside (SNP) in rat brain and liver tissues. The results showed that while PCA significantly (P<0.0001) inhibited the formation of TBARS in both liver and brain tissues homogenates, PCS did not. Further investigation reveals that the phenolic content of the PCS was significantly (P<0.0001) lower compared to PCA. Since phenolics in plants largely contributed to the antioxidative potency of plants, we conclude that air-drying should be employed in the preparation of extracts of Pitanga cherry leaves before it is administered empirically as a traditional medicament, and hence this study serves a public awareness to traditional medical practitioners.

  6. 18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of rats; the influence of time after injection, depressed lipid metabolism and glucose-insulin

    International Nuclear Information System (INIS)

    Kasalicky, J.; Konopkova, M.; Melichar, F.

    2001-01-01

    To study the effect of lipid depressing drugs on 18 FDG myocardial concentration. The changes of 18 FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. 5.55 MBq of 18 FDG were administered to Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following intravenous injection and the radioactivity concentration (cpm/g of tissue) in relation to injected cpm was determined in a well crystal adjusted to 511 KeV in order to check the time of maximal 18 FDG tissue uptake. The radioactivity in myocardium, skeletal muscle and brain in intact animals was compared with that of rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately before 18 FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before 18 FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before 18 FDG). The animals were killed 45 minutes following 18 FDG injection. Tyloxapol and acipimox significantly elevated myocardial 18 FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in 18 FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in 18 FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of 18 FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. The highest 18 FDG uptake in myocardium could be achieved by depressing the lipid metabolism and not by administration of glucose with insulin only. A marked increase in glucose accumulation in myocardium is not possible without previous shift from the utilisation of fatty acids. This finding is fully in agreement with present knowledge about energetic metabolism of myocardium. (author)

  7. Differential responses of brain, gonad and muscle steroid levels to changes in social status and sex in a sequential and bidirectional hermaphroditic fish.

    Directory of Open Access Journals (Sweden)

    Varenka Lorenzi

    Full Text Available Sex steroids can both modulate and be modulated by behavior, and their actions are mediated by complex interactions among multiple hormone sources and targets. While gonadal steroids delivered via circulation can affect behavior, changes in local brain steroid synthesis also can modulate behavior. The relative steroid load across different tissues and the association of these levels with rates of behavior have not been well studied. The bluebanded goby (Lythrypnus dalli is a sex changing fish in which social status determines sexual phenotype. We examined changes in steroid levels in brain, gonad and body muscle at either 24 hours or 6 days after social induction of protogynous sex change, and from individuals in stable social groups not undergoing sex change. For each tissue, we measured levels of estradiol (E(2, testosterone (T and 11-ketotestosterone (KT. Females had more T than males in the gonads, and more E(2 in all tissues but there was no sex difference in KT. For both sexes, E(2 was higher in the gonad than in other tissues while androgens were higher in the brain. During sex change, brain T levels dropped while brain KT increased, and brain E(2 levels did not change. We found a positive relationship between androgens and aggression in the most dominant females but only when the male was removed from the social group. The results demonstrate that steroid levels are responsive to changes in the social environment, and that their concentrations vary in different tissues. Also, we suggest that rapid changes in brain androgen levels might be important in inducing behavioral and/or morphological changes associated with protogynous sex change.

  8. Naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein partially purified from rat liver and rat brain membranes: an opioid/sigma receptor?

    Science.gov (United States)

    Tsao, L I; Su, T P

    1997-02-01

    A naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein was partially purified from rat liver and rat brain membranes in an affinity chromatography originally designed to purify sigma receptors. Detergent-solubilized extracts from membranes were adsorbed to Sephadex G-25 resin containing an affinity ligand for sigma receptors: N-(2- 3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl]) ethylamine (DAPE). After eluting the resin with haloperidol, a protein that bound [3H](+)SKF-10047 was detected in the eluates. However, the protein was not the sigma receptor. [3H](+)SKF-10047 binding to the protein was inhibited by the following compounds in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/-)cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (-)SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o-tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein. Tryptic digestion and heat treatment of the affinity-purified protein abolished radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of the partially-purified protein from the liver revealed a major diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and another polypeptide of > 97 kDa. This study demonstrates the existence of a novel protein in the rat liver and rat brain which binds opioids, benzomorphans, and haloperidol with namomolar affinity. The protein resembles the opioid/sigma receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther., 197:517-532.]. A high degree of purification of this protein has been achieved in the present study.

  9. Protective effect of serotonin on phospholipids and lipid peroxides contents in brain and liver of gamma irradiated rats

    International Nuclear Information System (INIS)

    Mohamed, M.A.; Saada, H.A.

    1999-01-01

    Treatment of normal rats with serotonin (2 mg/100 g body weight) produced no significant change in levels of phospholipids and lipid peroxides of the cerebral hemispheres and liver 1,3 and days after treatment. The content of lipid peroxides was measured as malondialdehyde (MDA). Whole body gamma-irradiation of rats at 8 Gy resulted in significant decrease in the level of phospholipids and significant increase in MDA level in cerebral hemispheres and lever. Changes were more pronounced in liver. Treatment with serotonin, 15 minutes before irradiation, had a pronounced protective effect against the radiation induced changes in the levels of phospholipids and MDA only in the liver through all the experimental period

  10. Comparative study of activities in reactive oxygen species production/defense system in mitochondria of rat brain and liver, and their susceptibility to methylmercury toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mori, N.; Hirayama, K. [Kumamoto University, School of Health Science, Kumamoto (Japan); Yasutake, A. [National Institute for Minamata Disease, Minamata (Japan)

    2007-11-15

    The involvement of oxidative stress has been suggested as a mechanism for neurotoxicity caused by methylmercury (MeHg), but the mechanism for MeHg selective toxicity in the central nervous system is still unclear. In this research, to clarify the mechanism of selective neurotoxicity caused by MeHg, the oxygen consumption levels, the reactive oxygen species (ROS) production rates and several antioxidant levels in mitochondria were compared among the cerebrum, cerebellum and liver of male Wistar rats. In addition, the alterations of these indexes were examined in MeHg-intoxicated rats (oral administration of 10 mg/kg day, for 5 days). Although the cerebrum and cerebellum in intact rats showed higher mitochondrial oxygen consumption levels and ROS production rates than the liver, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities were much lower in the cerebrum and cerebellum than in the liver. Especially, the cerebellum showed the highest oxygen consumption and ROS production rate and the lowest mitochondrial glutathione (GSH) levels among the tissues examined. In the MeHg-treated rats, decrease in the oxygen consumption and increase in the ROS generation were found only in the cerebellum mitochondria, despite a lower Hg accumulation in the mitochondrial fraction compared to the liver. Since MeHg treatment produced an enhancement of ROS generation in cerebellum mitochondria supplemented with succinate substrates, MeHg-induced oxidative stress might affect the complex II-III mediated pathway in the electron transfer chain in the cerebellum mitochondria. Our study suggested that inborn factors, high production system activity and low defense system activity of ROS in the brain, would relate to the high susceptibility of the central nervous system to MeHg toxicity. (orig.)

  11. Altered fast- and slow-twitch muscle fibre characteristics in female mice with a (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor.

    Science.gov (United States)

    Cannata, David J; Finkelstein, David I; Gantois, Ilse; Teper, Yaroslav; Drago, John; West, Jan M

    2009-01-01

    We generated a mouse line with a missense mutation (S248F) in the gene (CHRNA4) encoding the alpha4 subunit of neuronal nicotinic acetylcholine receptor (nAChR). Mutant mice demonstrate brief nicotine induced dystonia that resembles the clinical events seen in patients with the same mutation. Drug-induced dystonia is more pronounced in female mice, thus our aim was to determine if the S248F mutation changed the properties of fast- and slow-twitch muscle fibres from female mutant mice. Reverse transcriptase-PCR confirmed CHRNA4 gene expression in the brain but not skeletal muscles in normal and mutant mice. Ca(2+) and Sr(2+) force activation curves were obtained using skinned muscle fibres prepared from slow-twitch (soleus) and fast-twitch (EDL) muscles. Two significant results were found: (1) the (pCa(50) - pSr(50)) value from EDL fibres was smaller in mutant mice than in wild type (1.01 vs. 1.30), (2) the percentage force produced at pSr 5.5 was larger in mutants than in wild type (5.76 vs. 0.24%). Both results indicate a shift to slow-twitch characteristics in the mutant. This conclusion is supported by the identification of the myosin heavy chain (MHC) isoforms. Mutant EDL fibres expressed MHC I (usually only found in slow-twitch fibres) as well as MHC IIa. Despite the lack of spontaneous dystonic events, our findings suggest that mutant mice may be having subclinical events or the mutation results in a chronic alteration to muscle neural input.

  12. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats

    OpenAIRE

    Okkes YILMAZ; Yasemin ERSAN; Ayse Dilek OZSAHIN; Ali Ihsan OZTURK; Yusuf OZKAN

    2013-01-01

    Objective(s): Our objective was to evaluate the effects of a triple antioxidant combination [?-tocopherol (AT), ascorbic acid (AA) and ?-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. Materials and Methods: Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fou...

  13. Cloning and expression analysis of myostatin, fibroblast growth factor 6, insulin-like growth factor I and II in liver and muscle of sea bass (Dicentrarchus labrax, L. during long-term fasting and refeeding

    Directory of Open Access Journals (Sweden)

    M. Saroglia

    2010-04-01

    Full Text Available The exceptionally fast growth that fish experience after periods of fasting has been called “compensatory growth”. This phenomenon has been studied in intensive aquaculture as a means of enhancing growth rates, but the mechanisms by which food intake activates an increase in somatic growth, and especially in muscle growth, are complex and not yet fully understood. In the present paper, we describe the molecular cloning and sequencing of sea bass (Dicentrarchus labrax myostatin (MSTN and fibroblast growth factor 6 (FGF6, which have been shown to be major genetic determinants of skeletal muscle growth, together with insulin-like growth factor I (IGFI and IGF-II, which are potent mitogens known to play important roles in growth and development. We then report the pattern of expression of the four aforementioned genes, in liver and myotomal muscle in response to prolonged fasting and refeeding. Nutritional status significantly influenced the expression of IGF-I, IGF-II and MSTN, whereas the muscular FGF6 expression levels were not affected by the feeding status of the animals. Taken together these data indicate that IGF-I, IGF-II and MSTN are involved in the sea bass muscle compensatory growth induced by refeeding, whereas FGF6 probably has not a role in this phenomenon.

  14. Differential effects of dopamine and opioid receptor blockade on motivated Coca-Cola drinking behavior and associated changes in brain, skin and muscle temperatures.

    Science.gov (United States)

    Kiyatkin, E A

    2010-05-05

    Although pharmacological blockade of both dopamine (DA) and opiate receptors has an inhibiting effect on appetitive motivated behaviors, it is still unclear which physiological mechanisms affected by these treatments underlie the behavioral deficit. To clarify this issue, we examined how pharmacological blockade of either DA (SCH23390+eticlopride at 0.2 mg/kg each) or opioid receptors (naloxone 1 mg/kg) affects motor activity and temperature fluctuations in the nucleus accumbens (NAcc), temporal muscle, and facial skin associated with motivated Coca-Cola drinking behavior in rats. In drug-free conditions, presentation of a cup containing 5 ml of Coca-Cola induced locomotor activation and rapid NAcc temperature increases, which both transiently decreased during drinking, and phasically increased again after the cup was emptied. Muscle temperatures followed this pattern, but increases were weaker and more delayed than those in the NAcc. Skin temperature rapidly dropped after cup presentation, remained at low levels during consumption, and slowly restored during post-consumption behavioral activation. By itself, DA receptor blockade induced robust decrease in spontaneous locomotion, moderate increases in brain and muscle temperatures, and a relative increase in skin temperatures, suggesting metabolic activation coupled with adynamia. Following this treatment (approximately 180 min), motor activation to cup presentation and Coca-Cola consumption were absent, but rats showed NAcc and muscle temperature increases following cup presentation comparable to control. Therefore, DA receptor blockade does not affect significantly central and peripheral autonomic responses to appetitive stimuli, but eliminates their behavior-activating effects, thus disrupting appetitive behavior and blocking consumption. Naloxone alone slightly decreased brain and muscle temperatures and increased skin temperatures, pointing at the enhanced heat loss and possible minor inhibition of basal

  15. Liver Transplant

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  16. [Resting-state functional magnetic resonance study of brain function changes after TIPS operation in patients with liver cirrhosis].

    Science.gov (United States)

    Liu, C; Wang, H B; Yu, Y Q; Wang, M Q; Zhang, G B; Xu, L Y; Wu, J M

    2016-12-20

    Objective: To investigate the brain function changes in cirrhosis patients after transjugular intrahepatic portosystemic shunt (TIPS), resting-state functional MRI (rs-fMRI) performed and fractional amplitude of low frequency fluctuation (fALFF) was analyzed. Methods: From January 2014 to February 2016, a total of 96 cirrhotic patients from invasive technology department and infection department in the First Affiliated Hospital of Anhui Medical University were selected , the blood ammonia data of 96 cirrhotic patients with TIPS operation in four groups were collected after 1, 3, 6 and 12 month, and all subjects performed rs-fMRI scans. The rs-fMRI data processed with DPARSF and SPM12 softwares, whole-brain fALFF values were calculated, and One-Way analysis of variance , multiple comparison analysis and correlation analysis were performed. Results: There were brain regions with significant function changes in four groups patients with TIPS operation after 1, 3, 6 and 12 month, including bilateral superior temporal gyrus, right middle temportal gyrus , right hippocampus, right island of inferior frontal gyrus, left fusiform gyrus, left olfactory cortex, left orbital superior frontal gyrus (all P brain function areas increased in left olfactory cortex, left inferior temporal gyrus, left fusiform gyrus, left orbital middle frontal gyrus, left putamen, left cerebelum, and decreased in left lingual gyrus; patients in the 6-month follow-up showed that brain function areas increased in left middle temportal gyrus, right supramarginal gyrus, right temporal pole, right central operculum, and decreased in left top edge of angular gyrus, left postcentral gyrus; patients in the 12-month follow-up showed that brain function areas increased in right hippocampus, right middle cingulate gyrus, and decreased in right middle temportal gyrus.Compared with patients in the 3-month follow-up, patients in the 6-month follow-up showed that brain function areas increased in left superior

  17. A common pathway for regulation of nutritive blood flow to the brain: arterial muscle membrane potential and cytochrome P450 metabolites.

    Science.gov (United States)

    Harder, D R; Roman, R J; Gebremedhin, D; Birks, E K; Lange, A R

    1998-12-01

    Perfusion pressure to the brain must remain relatively constant to provide rapid and efficient distribution of blood to metabolically active neurones. Both of these processes are regulated by the level of activation and tone of cerebral arterioles. The active state of cerebral arterial muscle is regulated, to a large extent, by the level of membrane potential. At physiological levels of arterial pressure, cerebral arterial muscle is maintained in an active state owing to membrane depolarization, compared with zero pressure load. As arterial pressure changes, so does membrane potential. The membrane is maintained in a relatively depolarized state because of, in part, inhibition of K+ channel activity. The activity of K+ channels, especially the large conductance Ca(2+)-activated K+ channel (KCa) is dependent upon the level of 20-HETE produced by arterial muscle. As arterial pressure increases, so does cytochrome P450 (P4504A) activity. P4504A enzymes catalyse omega-hydroxylation of arachidonic acid and formation of 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE is a potent inhibitor of KCa which maintains membrane depolarization and muscle cell activation. Astrocytes also metabolize AA via P450 enzymes of the 2C11 gene family to produce epoxyeicosatrienoic acids (EETs). Epoxyeicosatrienoic acids are released from astrocytes by glutamate which 'spills over' during neuronal activity. These locally released EETs shunt blood to metabolically active neurones providing substrate to support neuronal function. This short paper will discuss the findings which support the above scenario, the purpose of which is to provide a basis for future studies on the molecular mechanisms through which cerebral blood flow matches metabolism.

  18. Brain, kidney and liver sup 203 Hg-methyl mercury uptake in the rat: Relationship to the neutral amino acid carrier

    Energy Technology Data Exchange (ETDEWEB)

    Aschner, M [Department of Pharmacology and Toxicology, and the Interdepartmental Neuroscience Training Program, Albany Medical College, Albany, NY (USA)

    1989-01-01

    To investigate the effect of L-neutral amino acids on tissue levels of methyl mercury in the adult animal, rats were infused into the external jugular vein with solutions containing (a) 0.05 mM {sup 203}Hg-MeHgCl and saline, (b) 0.05 mM {sup 203}Hg-MgHgCl-0.1 mM L-cysteine, (c) 0.05 mM {sup 203}Hg-MeHgCl-0.1 mM L-cysteine-0.1 mM L-methionine, (d) 0.05 mM {sup 203}Hg-MeHgCl-0.1 mM L-leucine, or (e) 0.05 mM {sup 203}Hg-MeHgCl-0.1 mM L-cysteine-0.1 mM L-leucine. Groups of animals were sacrificed at 3 min. 7 hr, and 96 hr. Brain, kidney, and liver {sup 203}Hg radioactivity was measured by means of gamma-scintillation spectrometry. Brain {sup 203}Hg concentrations L-cysteine treated animals were significantly higher compared with saline treated animals (P<0.05) at 3 min., 7 hr and 96 hr. The coinjection or coinfusion of methyl mercury with L-cysteine and L-methionine abolished the L-cysteine-mediated brain {sup 203}Hg uptake (P<0.05), at each sacrifice time. Kidney and liver {sup 203}Hg concentrations were not significantly different in any of the treatment groups compared with controls, irrespective of the sacrifice time. Furthermore, the percentage of diffusible {sup 203}Hg (non-protein bound) at each sacrifice time was not statistically different irrespective of the treatment assigned. These results suggest that methyl mercury L-cysteine conjugates in the plasma may share a common transport step with the L-neutral amino acid carrier transport system and indicate the presence in brain capillaries of a transport system capable of selectively mediating methyl mercury uptake across the capillary endothelial cell membrane. (author).

  19. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats.

    Science.gov (United States)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S; Simonsen, Mette; Ott, Peter; Vilstrup, Hendrik; Sørensen, Michael

    2014-03-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine, and aspartate and incorporation of (15)NH(4)(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation of (15)NH(4)(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH(4)(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increased incorporation of (15)N-ammonia into alanine observed. Liver and kidney were important for metabolizing blood-borne ammonia.

  20. Chemotactic and inflammatory responses in the liver and brain are associated with pathogenesis of Rift Valley fever virus infection in the mouse.

    Directory of Open Access Journals (Sweden)

    Kimberly K Gray

    Full Text Available Rift Valley fever virus (RVFV is a major human and animal pathogen associated with severe disease including hemorrhagic fever or encephalitis. RVFV is endemic to parts of Africa and the Arabian Peninsula, but there is significant concern regarding its introduction into non-endemic regions and the potentially devastating effect to livestock populations with concurrent infections of humans. To date, there is little detailed data directly comparing the host response to infection with wild-type or vaccine strains of RVFV and correlation with viral pathogenesis. Here we characterized clinical and systemic immune responses to infection with wild-type strain ZH501 or IND vaccine strain MP-12 in the C57BL/6 mouse. Animals infected with live-attenuated MP-12 survived productive viral infection with little evidence of clinical disease and minimal cytokine response in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion of lymphocytes and platelets and elicited a strong, systemic cytokine response which correlated with high virus titers and significant tissue pathology. Lymphopenia and platelet depletion were indicators of disease onset with indications of lymphocyte recovery correlating with increases in G-CSF production. RVFV is hepatotropic and in these studies significant clinical and histological data supported these findings; however, significant evidence of a pro-inflammatory response in the liver was not apparent. Rather, viral infection resulted in a chemokine response indicating infiltration of immunoreactive cells, such as neutrophils, which was supported by histological data. In brains of ZH501 infected mice, a significant chemokine and pro-inflammatory cytokine response was evident, but with little pathology indicating meningoencephalitis. These data suggest that RVFV pathogenesis in mice is associated with a loss of liver function due to liver necrosis and hepatitis yet the long-term course of disease for those that

  1. Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine.

    Science.gov (United States)

    Lee, Hyunsu; Park, Jae-Hyung; Seo, Incheol; Park, Sun-Hyun; Kim, Shin

    2014-12-21

    Mapping of tissue structure at the cellular, circuit, and organ-wide scale is important for understanding physiological and biological functions. A bio-electrochemical technique known as CLARITY used for three-dimensional anatomical and phenotypical mapping within transparent intact tissues has been recently developed. This method provided a major advance in understanding the structure-function relationships in circuits of the nervous system and organs by using whole-body clearing. Thus, in the present study, we aimed to improve the original CLARITY procedure and developed specific CLARITY protocols for various intact organs. We determined the optimal conditions for reducing bubble formation, discoloration, and depositing of black particles on the surface of tissue, which allowed production of clearer organ images. We also determined the appropriate replacement cycles of clearing solution for each type of organ, and convincingly demonstrated that 250-280 mA is the ideal range of electrical current for tissue clearing. We then acquired each type of cleared organs including brain, pancreas, liver, lung, kidney, and intestine. Additionally, we determined the images of axon fibers of hippocampal region, the Purkinje layer of cerebellum, and vessels and cellular nuclei of pancreas. CLARITY is an innovative biochemical technology for the structural and molecular analysis of various types of tissue. We developed improved CLARITY methods for clearing of the brain, pancreas, lung, intestine, liver, and kidney, and identified the appropriate experimental conditions for clearing of each specific tissue type. These optimized methods will be useful for the application of CLARITY to various types of organs.

  2. Introduction to the Thematic Minireview Series: Brain glycogen metabolism.

    Science.gov (United States)

    Carlson, Gerald M; Dienel, Gerald A; Colbran, Roger J

    2018-05-11

    The synthesis of glycogen allows for efficient intracellular storage of glucose molecules in a soluble form that can be rapidly released to enter glycolysis in response to energy demand. Intensive studies of glucose and glycogen metabolism, predominantly in skeletal muscle and liver, have produced innumerable insights into the mechanisms of hormone action, resulting in the award of several Nobel Prizes over the last one hundred years. Glycogen is actually present in all cells and tissues, albeit at much lower levels than found in muscle or liver. However, metabolic and physiological roles of glycogen in other tissues are poorly understood. This series of Minireviews summarizes what is known about the enzymes involved in brain glycogen metabolism and studies that have linked glycogen metabolism to multiple brain functions involving metabolic communication between astrocytes and neurons. Recent studies unexpectedly linking some forms of epilepsy to mutations in two poorly understood proteins involved in glycogen metabolism are also reviewed. © 2018 Carlson et al.

  3. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Directory of Open Access Journals (Sweden)

    Angeliki Lyssimachou

    Full Text Available Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT, which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR and peroxisome proliferator-activated receptor gamma (PPARγ. In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  4. The Mammalian “Obesogen” Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G.; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C. Marisa R.; Teixeira, Catarina; Castro, L. Filipe C.; Santos, Miguel M.

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an “obesogenic” phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound. PMID:26633012

  5. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C Marisa R; Teixeira, Catarina; Castro, L Filipe C; Santos, Miguel M

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  6. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats

    Science.gov (United States)

    YILMAZ, Okkes; ERSAN, Yasemin; Dilek OZSAHIN, Ayse; Ihsan OZTURK, Ali; OZKAN, Yusuf

    2013-01-01

    Objective(s): Our objective was to evaluate the effects of a triple antioxidant combination [α-tocopherol (AT), ascorbic acid (AA) and α-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. Materials and Methods: Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fourth and fifth groups were injected with intraperitoneal (IP) 50 mg/kg DL-AT and 50 mg /kg DL-LA four times per week and received water-soluble vitamin C (50 mg/kg) in their drinking water for a period of six weeks. Results: Liver cholesterol levels in the AT+AA+LA group were lower than the control (P<0.05). Glutathione level was lower in D-2 (P<0.05) and were higher in D+AT+AA+LA and AT+AA+LA groups than the control groups (P≤ 0.05). The muscle cholesterol levels in the D-1 and D+AT+AA+LA groups were higher than the control group (P≤ 0.05). The levels of oleic acid were higher in the D-1 group and lower in the D-2 group (P<0.001). The arachidonic acid level in the D-1 and D-2 groups were lower (P<0.05), and higher in the D+AT+AA+LA group. Conclusion: Our results revealed that glutathione levels and the Stearoyl CoA Desaturase enzyme products in liver tissues of diabetic and non-diabetic rats were increased by triple antioxidant mixture. PMID:24298385

  7. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats.

    Science.gov (United States)

    Yilmaz, Okkes; Ersan, Yasemin; Dilek Ozsahin, Ayse; Ihsan Ozturk, Ali; Ozkan, Yusuf

    2013-02-01

    Our objective was to evaluate the effects of a triple antioxidant combination [α-tocopherol (AT), ascorbic acid (AA) and α-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fourth and fifth groups were injected with intraperitoneal (IP) 50 mg/kg DL-AT and 50 mg /kg DL-LA four times per week and received water-soluble vitamin C (50 mg/kg) in their drinking water for a period of six weeks. Liver cholesterol levels in the AT+AA+LA group were lower than the control (Pcholesterol levels in the D-1 and D+AT+AA+LA groups were higher than the control group (P≤ 0.05). The levels of oleic acid were higher in the D-1 group and lower in the D-2 group (Pacid level in the D-1 and D-2 groups were lower (P<0.05), and higher in the D+AT+AA+LA group. Our results revealed that glutathione levels and the Stearoyl CoA Desaturase enzyme products in liver tissues of diabetic and non-diabetic rats were increased by triple antioxidant mixture.

  8. Perfusion CT of the Brain and Liver and of Lung Tumors: Use of Monte Carlo Simulation for Patient Dose Estimation for Examinations With a Cone-Beam 320-MDCT Scanner.

    Science.gov (United States)

    Cros, Maria; Geleijns, Jacob; Joemai, Raoul M S; Salvadó, Marçal

    2016-01-01

    The purpose of this study was to estimate the patient dose from perfusion CT examinations of the brain, lung tumors, and the liver on a cone-beam 320-MDCT scanner using a Monte Carlo simulation and the recommendations of the International Commission on Radiological Protection (ICRP). A Monte Carlo simulation based on the Electron Gamma Shower Version 4 package code was used to calculate organ doses and the effective dose in the reference computational phantoms for an adult man and adult woman as published by the ICRP. Three perfusion CT acquisition protocols--brain, lung tumor, and liver perfusion--were evaluated. Additionally, dose assessments were performed for the skin and for the eye lens. Conversion factors were obtained to estimate effective doses and organ doses from the volume CT dose index and dose-length product. The sex-averaged effective doses were approximately 4 mSv for perfusion CT of the brain and were between 23 and 26 mSv for the perfusion CT body protocols. The eye lens dose from the brain perfusion CT examination was approximately 153 mGy. The sex-averaged peak entrance skin dose (ESD) was 255 mGy for the brain perfusion CT studies, 157 mGy for the lung tumor perfusion CT studies, and 172 mGy for the liver perfusion CT studies. The perfusion CT protocols for imaging the brain, lung tumors, and the liver performed on a 320-MDCT scanner yielded patient doses that are safely below the threshold doses for deterministic effects. The eye lens dose, peak ESD, and effective doses can be estimated for other clinical perfusion CT examinations from the conversion factors that were derived in this study.

  9. Decreased spontaneous activity in AMPK alpha 2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism

    DEFF Research Database (Denmark)

    Møller, Lisbeth Liliendal Valbjørn; Sylow, Lykke; Gøtzsche, Casper René

    2016-01-01

    was tested in an open field test. Furthermore, we investigated maximal running capacity and voluntary running over a period of 19 days. AMPK α2 KD mice ran 30% less in daily distance compared to WT. Furthermore, AMPK α2 KD mice showed significantly decreased locomotor activity in the open field test compared...... through alterations of the brain dopamine levels specifically in the striatal region. To test this hypothesis, transgenic mice overexpressing an inactivatable dominant negative α2 AMPK construct (AMPK α2 KD) in muscles and littermate wildtype (WT) mice were tested. AMPK α2 KD mice have impaired running...... capacity and display reduced voluntary wheel running activity. Striatal content of dopamine and its metabolites were measured under basal physiological conditions and after cocaine-induced dopamine efflux from the ventral striatum by in vivo microdialysis. Moreover, cocaine-induced locomotor activity...

  10. Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men.

    Science.gov (United States)

    Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik; Vranes, Milan

    2016-09-01

    In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P creatine for improved bioenergetics in energy-demanding tissues.

  11. Effect of different commercial fat sources on brain, liver and blood lipid profiles of rats in growth phase

    OpenAIRE

    Angelis-Pereira, Michel Cardoso de; Barcelos, Maria de Fátima Píccolo; Pereira, Juciane de Abreu Ribeiro; Pereira, Rafaela Corrêa; Souza, Raimundo Vicente de

    2017-01-01

    Abstract Purpose: To investigate the fatty acid content of different fat sources and evaluate the effect of them on plasma and hepatic lipids and on the fatty acid profile of the brain tissue of Wistar rats. Methods: Thirty male albino Wistar rats received for 59 days, the following diets: diet added of margarine with low content of polyunsaturated fatty acids (PUFA); diet added of margarine with high content of PUFA; diet added of butter; diet added of hydrogenated vegetable fat; diet ad...

  12. Society of cardiovascular anesthesiologists: the effect of blood pressure regulation during aortic coarctation repair on brain, kidney, and muscle oxygen saturation measured by near-infrared spectroscopy: a randomized, clinical trial

    NARCIS (Netherlands)

    Moerman, Annelies; Bové, Thierry; François, Katrien; Jacobs, Stefan; Deblaere, Isabel; Wouters, Patrick; de Hert, Stefan

    2013-01-01

    In this study, we compared the effects of 3 frequently used arterial blood pressure-regulating agents on brain (rScO2), renal (SrO2), and muscle (SmO2) oxygen saturation, during aortic coarctation repair in children. Based on the reported adverse effect of sodium nitroprusside (SNP) on left-sided

  13. In vivo vitamin C deficiency in guinea pigs increases ascorbate transporters in liver but not kidney and brain.

    Science.gov (United States)

    Søgaard, Ditte; Lindblad, Maiken M; Paidi, Maya D; Hasselholt, Stine; Lykkesfeldt, Jens; Tveden-Nyborg, Pernille

    2014-07-01

    Moderate vitamin C (vitC) deficiency (plasma concentrations less than 23 μmol/L) affects as much as 10% of adults in the Western World and has been associated with an increased mortality in disease complexes such as cardiovascular disease and the metabolic syndrome. The distribution of vitC within the body is subjected to complex and nonlinear pharmacokinetics and largely depends on the sodium-dependent vitC-specific transporters, sodium-dependent vitamin C transporter 1 (SVCT1) and sodium-dependent vitamin C transporter 2 (SVCT2). Although currently not established, it is likely to expect that a state of deficiency may affect the expression of these transporters to preserve vitC concentrations in specific target tissues. We hypothesized that diet-induced states of vitC deficiency lead to alterations in the messenger RNA (mRNA) and/or protein expression of vitC transporters, thereby regulating vitC tissue distribution. Using guinea pigs as a validated model, this study investigated the effects of a diet-induced vitC deficiency (100 mg vitC/kg feed) or depletion (0 mg vitC/kg feed) on the expression of transporters SVCT1 and SVCT2 in selected tissues and the transport from plasma to cerebrospinal fluid (CSF). In deficient animals, SVCT1 was increased in the liver, whereas a decreased SVCT1 expression but increased SVCT2 mRNA in livers of depleted animals suggests a shift in transporter expression as response to the diet. In CSF, a constant plasma:CSF ratio shows unaltered vitC transport irrespective of dietary regime. The study adds novel information to the complex regulation maintaining vitC homeostasis in vivo during states of deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The effects of X-irradiation, N-ethyl-N-nitrosourea or combined treatment on O6-alkylguanine-DNA alkyltransferase activity in fetal rat brain and liver and the induction of CNS tumours

    International Nuclear Information System (INIS)

    Stammberger, I.; Nice, L.; Schmahl, W.

    1990-01-01

    Wistar rats were treated in utero on day 16 of gestation either by X-irradiation, N-ethyl-N-nitrosourea (ENU), or both in combination. The O 6 -alkylguanine-DNA alkyltransferase (AT) activity of the fetal brain and liver was analyzed and long-term observations were made to reveal any relationship between the O 6 -ethylguanine repair capability and tumour incidence in the organs of the offspring. The AT activity in the brain was affected to the same extent in the fetuses as in the dams. There was a 60.9% decrease in AT activity in fetuses 24 h after ENU treatment. This correlates with a significant increase in the incidence of brain tumours in the treated offspring (44.1%) compared to control animals. The inductive effect of X-irradiation on AT activity corresponded in turn with a reduction of the incidence of tumours after the combined treatment. In the liver of the rat fetuses, there was generally no effect of treatment on AT activity in contrast to the results obtained for the dams, where an increased AT activity was observed. There were no tumours of the liver observed in the offspring after either treatment alone or after combined treatment. It is suggested that the combined treatment of rat fetuses could significantly reduce the incidence of brain tumours in adult life. (author)

  15. The effects of X-irradiation, N-ethyl-N-nitrosourea or combined treatment on O sup 6 -alkylguanine-DNA alkyltransferase activity in fetal rat brain and liver and the induction of CNS tumours

    Energy Technology Data Exchange (ETDEWEB)

    Stammberger, I.; Nice, L. (Muenchen Univ. (Germany, F.R.). Walter-Straub-Institut fuer Pharmakologie und Toxikologie); Schmahl, W. (Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Neuherberg (Germany, F.R.). Inst. fuer Pathologie)

    1990-02-01

    Wistar rats were treated in utero on day 16 of gestation either by X-irradiation, N-ethyl-N-nitrosourea (ENU), or both in combination. The O{sup 6}-alkylguanine-DNA alkyltransferase (AT) activity of the fetal brain and liver was analyzed and long-term observations were made to reveal any relationship between the O{sup 6}-ethylguanine repair capability and tumour incidence in the organs of the offspring. The AT activity in the brain was affected to the same extent in the fetuses as in the dams. There was a 60.9% decrease in AT activity in fetuses 24 h after ENU treatment. This correlates with a significant increase in the incidence of brain tumours in the treated offspring (44.1%) compared to control animals. The inductive effect of X-irradiation on AT activity corresponded in turn with a reduction of the incidence of tumours after the combined treatment. In the liver of the rat fetuses, there was generally no effect of treatment on AT activity in contrast to the results obtained for the dams, where an increased AT activity was observed. There were no tumours of the liver observed in the offspring after either treatment alone or after combined treatment. It is suggested that the combined treatment of rat fetuses could significantly reduce the incidence of brain tumours in adult life. (author).

  16. Arsenic and nicotine co-exposure lead to some synergistic effects on oxidative stress and apoptotic markers in young rat blood, liver, kidneys and brain

    Directory of Open Access Journals (Sweden)

    Anshu Jain

    2015-01-01

    Full Text Available Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water or nicotine (0.25 mg/kg, sub-cutaneously for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism in male rats.

  17. Effect of different commercial fat sources on brain, liver and blood lipid profiles of rats in growth phase.

    Science.gov (United States)

    Angelis-Pereira, Michel Cardoso de; Barcelos, Maria de Fátima Píccolo; Pereira, Juciane de Abreu Ribeiro; Pereira, Rafaela Corrêa; Souza, Raimundo Vicente de

    2017-12-01

    To investigate the fatty acid content of different fat sources and evaluate the effect of them on plasma and hepatic lipids and on the fatty acid profile of the brain tissue of Wistar rats. Thirty male albino Wistar rats received for 59 days, the following diets: diet added of margarine with low content of polyunsaturated fatty acids (PUFA); diet added of margarine with high content of PUFA; diet added of butter; diet added of hydrogenated vegetable fat; diet added of soybean oil. Fatty acid profile of the lipid sources, blood and hepatic lipids fractions and fatty acid profile of the brain tissue were determined. Margarine consumption of provided different responses as to concentrations of blood and hepatic lipid fractions. Intake of butter and hydrogenated increased LDL-c/HDL-c ratio, being the steepest increase promoted by hydrogenated vegetable fat, which also raised LDL-c levels expressively. All fats used in the treatments reduced the cerebral concentration of docosahexaenoic acid when compared to soybean oil (control). The different fat sources commonly consumed by population provided different responses in vivo. This is particularly relevant considering the role of these lipids in the incidence and prevention of cardiovascular diseases.

  18. Mitochondrial mosaics in the liver of 3 infants with mtDNA defects

    Directory of Open Access Journals (Sweden)

    Scalais Emmanuel

    2009-06-01

    Full Text Available Abstract Background In muscle cytochrome oxidase (COX negative fibers (mitochondrial mosaics have often been visualized. Methods COX activity staining of liver for light and electron microscopy, muscle stains, blue native gel electrophoresis and activity assays of respiratory chain proteins, their immunolocalisation, mitochondrial and nuclear DNA analysis. Results Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70%. Mutations in the nuclear encoded gene of POLG were subsequently found in both the 2nd and 3rd patients. Conclusion Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent

  19. Tissue oxygenation in brain, muscle, and fat in a rat model of sleep apnea: differential effect of obstructive apneas and intermittent hypoxia.

    Science.gov (United States)

    Almendros, Isaac; Farré, Ramon; Planas, Anna M; Torres, Marta; Bonsignore, Maria R; Navajas, Daniel; Montserrat, Josep M

    2011-08-01

    To test the hypotheses that the dynamic changes in brain oxygen partial pressure (PtO(2)) in response to obstructive apneas or to intermittent hypoxia differ from those in other organs and that the changes in brain PtO(2) in response to obstructive apneas is a source of oxidative stress. Prospective controlled animal study. University laboratory. 98 Sprague-Dawley rats. Cerebral cortex, skeletal muscle, or visceral fat tissues were exposed in anesthetized animals subjected to either obstructive apneas or intermittent hypoxia (apneic and hypoxic events of 15 s each and 60 events/h) for 1 h. Arterial oxygen saturation (SpO(2)) presented a stable pattern, with similar desaturations during both stimuli. The PtO(2) was measured by a microelectrode. During obstructive apneas, a fast increase in cerebral PtO(2) was observed (38.2 ± 3.4 vs. 54.8 ± 5.9 mm Hg) but not in the rest of tissues. This particular cerebral response was not found during intermittent hypoxia. The cerebral content of reduced glutathione was decreased after obstructive apneas (46.2% ± 15.2%) compared to controls (100.0% ± 14.7%), but not after intermittent hypoxia. This antioxidant consumption after obstructive apneas was accompanied by increased cerebral lipid peroxidation under this condition. No changes were observed for these markers in the other tissues. These results suggest that cerebral cortex could be protected in some way from hypoxic periods caused by obstructive apneas. The increased cerebral PtO(2) during obstructive apneas may, however, cause harmful effects (oxidative stress). The obstructive apnea model appears to be more adequate than the intermittent hypoxia model for studying brain changes associated with OSA.

  20. Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue.

    Science.gov (United States)

    Miao, Yifei; Wu, Wanfu; Dai, Yubing; Maneix, Laure; Huang, Bo; Warner, Margaret; Gustafsson, Jan-Åke

    2015-11-10

    The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

  1. The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial.

    Science.gov (United States)

    Blanco-Rojo, Ruth; Alcala-Diaz, Juan F; Wopereis, Suzan; Perez-Martinez, Pablo; Quintana-Navarro, Gracia M; Marin, Carmen; Ordovas, Jose M; van Ommen, Ben; Perez-Jimenez, Francisco; Delgado-Lista, Javier; Lopez-Miranda, Jose

    2015-10-16

    The aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function. The study was performed in 642 patients included in The effect of an olive oil rich Mediterranean diet on type 2 diabetes mellitus risk and incidence study (CORDIOPREV-DIAB). A total of 327 patients were randomised to a Mediterranean diet (35% fat; 22% from monounsaturated fatty acids) and 315 to a low-fat diet (Economia y Competitividad (AGL2012/39615) and by the Ministerio de Ciencia e Innovacion (PIE14/00005 and PI13/00023).

  2. Bioinformatical Analysis of Organ-Related (Heart, Brain, Liver, and Kidney and Serum Proteomic Data to Identify Protein Regulation Patterns and Potential Sepsis Biomarkers

    Directory of Open Access Journals (Sweden)

    Andreas Hohn

    2018-01-01

    Full Text Available During the last years, proteomic studies have revealed several interesting findings in experimental sepsis models and septic patients. However, most studies investigated protein alterations only in single organs or in whole blood. To identify possible sepsis biomarkers and to evaluate the relationship between protein alteration in sepsis affected organs and blood, proteomics data from the heart, brain, liver, kidney, and serum were analysed. Using functional network analyses in combination with hierarchical cluster analysis, we found that protein regulation patterns in organ tissues as well as in serum are highly dynamic. In the tissue proteome, the main functions and pathways affected were the oxidoreductive activity, cell energy generation, or metabolism, whereas in the serum proteome, functions were associated with lipoproteins metabolism and, to a minor extent, with coagulation, inflammatory response, and organ regeneration. Proteins from network analyses of organ tissue did not correlate with statistically significantly regulated serum proteins or with predicted proteins of serum functions. In this study, the combination of proteomic network analyses with cluster analyses is introduced as an approach to deal with high-throughput proteomics data to evaluate the dynamics of protein regulation during sepsis.

  3. 3D map of theranostic nanoparticles distribution in mice brain and liver by means of X-ray Phase Contrast Tomography

    Science.gov (United States)

    Longo, E.; Bravin, A.; Brun, F.; Bukreeva, I.; Cedola, A.; Fratini, M.; Le Guevel, X.; Massimi, L.; Sancey, L.; Tillement, O.; Zeitoun, P.; de La Rochefoucauld, O.

    2018-01-01

    The word "theranostic" derives from the fusion of two terms: therapeutic and diagnostic. It is a promising research field that aims to develop innovative therapies with high target specificity by exploiting the therapeutic and diagnostic properties, in particular for metal-based nanoparticles (NPs) developed to erase cancer. In the framework of a combined research program on low dose X-ray imaging and theranostic nanoparticles (NPs), high resolution Phase-Contrast Tomography images of mice organs injected with gadolinium and gold-NPs were acquired at the European Synchrotron Radiation Facility (ESRF). Both compounds are good X-ray contrast agents due to their high attenuation coefficient with respect to biological tissues, especially immediately above K-edge energy. X-ray tomography is a powerful non-invasive technique to image the 3D vasculature network in order to detect abnormalities. Phase contrast methods provide more detailed anatomical information with higher discrimination among soft tissues. We present the images of mice liver and brain injected with gold and gadolinium NPs, respectively. We discuss different image processing methods used aiming at enhancing the accuracy on localizing nanoparticles.

  4. Aluminium sulfate exposure: A set of effects on hydrolases from brain, muscle and digestive tract of juvenile Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Oliveira, Vagne Melo; Assis, Caio Rodrigo Dias; Costa, Helane Maria Silva; Silva, Raquel Pereira Freitas; Santos, Juliana Ferreira; Carvalho, Luiz Bezerra; Bezerra, Ranilson Souza

    2017-01-01

    Aluminium is a major pollutant due to its constant disposal in aquatic environments through anthropogenic activities. The physiological effects of this metal in fish are still scarce in the literature. This study investigated the in vivo and in vitro effects of aluminium sulfate on the activity of enzymes from Nile tilapia (Oreochromis niloticus): brain acetylcholinesterase (AChE), muscle cholinesterases (AChE-like and BChE-like activities), pepsin, trypsin, chymotrypsin and amylase. Fish were in vivo exposed during 14days when the following experimental groups were assayed: control group (CG), exposure to Al 2 (SO 4 ) 3 at 1μg·mL -1 (G1) and 3μg·mL -1 (G3) (concentrations compatible with the use of aluminium sulfate as coagulant in water treatment). In vitro exposure was performed using animals of CG treatment. Both in vivo and in vitro exposure increased cholinesterase activity in relation to controls. The highest cholinesterase activity was observed for muscle BChE-like enzyme in G3. In contrast, the digestive enzymes showed decreased activity in both in vivo and in vitro exposures. The highest inhibitory effect was observed for pepsin activity. The inhibition of serine proteases was also quantitatively analyzed in zymograms using pixel optical densitometry as area under the peaks (AUP) and integrated density (ID). These results suggest that the inhibition of digestive enzymes in combination with activation of cholinesterases in O. niloticus is a set of biochemical effects that evidence the presence of aluminium in the aquatic environment. Moreover, these enzymatic alterations may support further studies on physiological changes in this species with implications for its neurological and digestive metabolisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Liver Hemangioma

    Science.gov (United States)

    Liver hemangioma Overview A liver hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass in the liver. A liver hemangioma is made up of a tangle of blood vessels. Other terms for a liver hemangioma are hepatic hemangioma and cavernous hemangioma. Most ...

  6. Nutritional support of children with chronic liver disease

    African Journals Online (AJOL)

    The effect that chronic liver disease has on a child's nutritional status and ... even children with less severe liver disease require nutritional .... Reduced muscle bulk .... pain and fractures, palpation of the spine and assessment of pubertal stage.

  7. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  8. Primary hydatid cyst in gastrocnemius muscle

    Directory of Open Access Journals (Sweden)

    Saswata Bharati

    2012-01-01

    Full Text Available Cystic echinococcosis, which is caused by the larval stages of Echinococcus granulosus, results from the presence of one or more massive cysts or hydatids, and can involve any organ, including the liver, lungs, heart, brain, kidneys, and long bones. Muscle hydatidosis is usually secondary in nature, resulting from spread of larval tissue from a primary site after spontaneous or trauma-induced cyst rupture or after release of viable parasite material during invasive treatment procedures. Primary muscle hydatidosis is extremely uncommon, because implantation at this site would require passage through the filters of the liver and lung. Intramuscular hydatid cyst can cause a variety of diagnostic problems, especially in the absence of typical radiologic findings. We present an unusual case of a primary hydatid cyst found in the popliteal fossa of the right knee of a 52-year-old woman, presenting as an enlarging soft-tissue tumor for 6 months associated with pain. The mass initially was diagnosed to be Backer′s cyst by ultrasonography, but later it was confirmed postoperatively through histopathological studies to be due to hydatid disease. In regions where hydatidosis is endemic, hydatid cyst should be included in the differential diagnosis of any unusual muscular mass.

  9. Mice Lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are Protected Against Conjugated Linoleic Acid-Induced Fatty Liver but Develop Inflammation and Insulin Resistance in the Brain.

    Science.gov (United States)

    Sartorius, Tina; Drescher, Andrea; Panse, Madhura; Lastovicka, Petr; Peter, Andreas; Weigert, Cora; Kostenis, Evi; Ullrich, Susanne; Häring, Hans-Ulrich

    2015-01-01

    Conjugated linoleic acids (CLAs) affect body fat distribution, induce insulin resistance and stimulate insulin secretion. The latter effect is mediated through the free fatty acid receptor-1 (GPR40/FFAR1). This study examines whether GPR40/FFAR1 interacts with tissue specific metabolic changes induced by CLAs. After chronic application of CLAs C57BL/6J wild type (WT) and GPR40/FFAR1 (Ffar1(-/-)) knockout mice developed insulin resistance. Although CLAs accumulated in liver up to 46-fold genotype-independently, hepatic triglycerides augmented only in WT mice. This triglyceride deposition was not associated with increased inflammation. In contrast, in brain of CLA fed Ffar1(-/-) mice mRNA levels of TNF-α were 2-fold higher than in brain of WT mice although CLAs accumulated genotype-independently in brain up to 4-fold. Concomitantly, Ffar1(-/-) mice did not respond to intracerebroventricular (i.c.v.) insulin injection with an increase in cortical activity while WT mice reacted as assessed by radiotelemetric electrocorticography (ECoG) measurements. In vitro incubation of primary murine astrocytes confirmed that CLAs stimulate neuronal inflammation independent of GPR40/FFAR1. This study discloses that GPR40/FFAR1 indirectly modulates organ-specific effects of CLAs: the expression of functional GPR40/FFAR1 counteracts CLA-induced inflammation and insulin resistance in the brain, but favors the development of fatty liver. © 2015 S. Karger AG, Basel.

  10. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Matthews, V B; Åström, Maj-Brit; Chan, M H S

    2009-01-01

    C12 skeletal muscle cells were electrically stimulated to mimic contraction. L6 myotubes and isolated rat extensor digitorum longus muscles were treated with BDNF and phosphorylation of the proteins AMP-activated protein kinase (AMPK) (Thr(172)) and acetyl coenzyme A carboxylase beta (ACCbeta) (Ser...... kinase (p44/42 Thr(202)/Tyr(204)) phosphorylation in these muscles. In addition, phosphorylation of ACCbeta was markedly elevated in the Bdnf electroporated muscles. CONCLUSIONS/INTERPRETATION: These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing...

  11. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...

  12. Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor 1

    DEFF Research Database (Denmark)

    Bisgaard, H.C.; Holmskov, U.; Santoni-Rugiu, E.

    2002-01-01

    The regenerative capacity of mammalian adult liver reflects the ability of a number of cell populations within the hepatic lineage to take action. Limited information is available regarding factors and mechanisms that determine the specific lineage level at which liver cells contribute to liver......), were specifically associated with the emergence of ductular (oval) cell populations in injured liver. Subsequent cloning and characterization of the rat DMBT1 homologue revealed a highly inducible expression in ductular reactions composed of transit-amplifying ductular (oval) cells, but not in ductular...... reactions after ligation of the common bile duct. In human liver diseases, DMBT1 was expressed in ductular reactions after infection with hepatitis B and acetaminophen intoxication, but not in primary biliary cirrhosis, primary sclerosing cholangitis, and obstruction of the large bile duct. The expression...

  13. Autoimmune liver disease 2007.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

    2008-01-01

    Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

  14. O2 supplementation to secure the near-infrared spectroscopy determined brain and muscle oxygenation in vascular surgical patients: a presentation of 100 cases

    Directory of Open Access Journals (Sweden)

    Kim Zillo Rokamp

    2014-02-01

    Full Text Available This study addresses three questions for securing tissue oxygenation in brain (rScO2 and muscle (SmO2 for 100 patients (age 71 ± 6 yrs; mean ± SD undergoing vascular surgery: i Does preoxygenation (inhaling 100% oxygen before anesthesia increase tissue oxygenation, ii Does inhalation of 70% oxygen during surgery prevent a critical reduction in rScO2 (< 50%, and iii is a decrease in rScO2 and/or SmO2 related to reduced blood pressure and/or cardiac output? Intravenous anesthesia was provided to all patients and the intraoperative inspired oxygen fraction was set to 0.70 while tissue oxygenation was determined by INVOS 5100C. Preoxygenation increased rScO2 (from 65 ± 8% to 72 ± 9%; P < 0.05 and SmO2 (from 75 ± 9% to 78 ± 9%; P < 0.05 and during surgery rScO2 and SmO2 were maintained at the baseline level in most patients. Following anesthesia and tracheal intubation an eventual change in rScO2 correlated to cardiac output and cardiac stroke volume (coefficient of contingence=0.36; P=0.0003 rather to a change in mean arterial pressure and for five patients rScO2 was reduced to below 50%. We conclude that i increased oxygen delivery enhances tissue oxygenation, ii oxygen supports tissue oxygenation but does not prevent a critical reduction in cerebral oxygenation sufficiently, and iii an eventual decrease in tissue oxygenation seems related to a reduction in cardiac output rather than to hypotension.

  15. Gene cloning and mRNA expression of glutamate dehydrogenase in the liver, brain and intestine of the swamp eel, Monopterus albus, exposed to freshwater, terrestrial conditions, environmental ammonia or salinity stress

    Directory of Open Access Journals (Sweden)

    C Y Toh

    2011-12-01

    Full Text Available The swamp eel, Monopterus albus, is an obligatory air-breathing teleost which can survive long period of emersion, has high environmental and tissue ammonia tolerance, and acclimate from fresh to brackish water. This study was undertaken to clone and sequence gdh expressed in the liver, intestine and brain of M. albus, to verify whether more than one form of gdh were expressed, and to examine the gdh mRNA expressions in these three organs in fish exposed to various adverse conditions using quantitative real-time PCR. Only one gdh gene sequence, consisted of a 133 bp 5’ UTR, a CDS region spanning 1629 bp and a 3’ UTR of approximately 717 bp, was obtained from the liver, intestine and brain of M. albus. The translated Gdh amino acid sequence from the liver of M. albus had 542 residues and was confirmed to be Gdh1a. It had sequence identity of >90% with Oncorhynchus mykiss Gdh1a, Salmo salar Gdh1a1, Bostrychus sinensis Gdh1a and Tribolodon hakonensis Gdh1a, and formed a monophyletic clade with B. sinensis Gdh1a, Tetraodon nigroviridis Gdh1a, Chaenocephalus aceratus Gdh1a, Salmo salar Gdh1a1 and Gdh1a2 and O. mykiss Gdh1a. An increase in mRNA expression of gdh1a could be essential for increased glutamate production in support of increases in glutamine synthesis under certain environmental condition. Indeed, exposure of M. albus to 1 day of terrestrial conditions or 75 mmol l-1 NH4Cl, but not brackish water, resulted in a significant increase in gdh1a mRNA expression in the liver. However, exposure to brackish water, but not terrestrial conditions or 75 mmol l-1 NH4Cl, lead to a significant increase in the intestinal mRNA expression of gdh1a. By contrast, all the three experimental conditions had no significant effects on the mRNA expression of gdh1a in the brain of M. albus. Our results indicate for the first time that gdh mRNA expression was differentially up-regulated in the liver and intestine of M. albus, in responses to ammonia toxicity and

  16. Muscles and their myokines.

    Science.gov (United States)

    Pedersen, Bente Klarlund

    2011-01-15

    In the past, the role of physical activity as a life-style modulating factor has been considered as that of a tool to balance energy intake. Although it is important to avoid obesity, physical inactivity should be discussed in a much broader context. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular diseases, cancer, dementia and even depression. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an 'exercise factor', which could be released from skeletal muscle during contraction and mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We have suggested that cytokines or other peptides that are produced, expressed and released by muscle fibres and exert autocrine, paracrine or endocrine effects should be classified as 'myokines'. Given that skeletal muscle is the largest organ in the human body, our discovery that contracting skeletal muscle secretes proteins sets a novel paradigm: skeletal muscle is an endocrine organ producing and releasing myokines, which work in a hormone-like fashion, exerting specific endocrine effects on other organs. Other myokines work via paracrine mechanisms, exerting local effects on signalling pathways involved in muscle metabolism. It has been suggested that myokines may contribute to exercise-induced protection against several chronic diseases.

  17. Muscle Deoxygenation Causes Muscle Fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

    1999-01-01

    Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.

  18. Magnetic resonance imaging (MRI) of liver and brain in haematologic-organic patients with fever of unknown origin; Magnetresonanztomographie (MRT) der Leber und des Gehirns bei haematologisch-onkologischen Patienten mit Fieber unbekannter Ursache

    Energy Technology Data Exchange (ETDEWEB)

    Heussel, C.P.; Kauczor, H.U.; Poguntke, M.; Schadmand-Fischer, S.; Mildenberger, P.; Thelen, M. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Radiologie; Heussel, G. [Mainz Univ. (Germany). 3. Medizinische Klinik und Poliklinik

    1998-08-01

    To examine the advantage of liver and brain MRI in clinically anomalous haematological patients with fever of unknown origin. Material and Methods: Twenty liver MRI (T{sub 2}-TSE, T{sub 2}-HASTE, T{sub 1}-FLASH{+-}Gd dynamic) and 16 brain MRI (T{sub 2}-TSE, FLAIR, T{sub 1}-TSE{+-}Gd) were performed searching for a focus of fever with a suspected organ system. Comparison with clinical follow-up. Results: suspected organ system. Comparison with clinical follow-up. Results: A focus was detected in 11/20 liver MRI. Candidiasis (n=3), mycobacteriosis (n=2), relapse of haematological disease (n=3), graft versus host disease (n=1), non-clarified (n=2). The remaining 9 cases with normal MRI were not suspicious of infectious hepatic disease during follo-wup. In brain MRI, 3/16 showed a focus (toxoplasmosis, aspergillosis, mastoiditis). Clinical indication for an infectious involvement of the brain was found in 4/16 cases 2--5 months after initially normal brain MRI. No suspicion of an infectious involvement of brain was present in the remaining 9/16 cases. Conclusion: In case of fever of unknown origin and suspicion of liver involvement, MRI of the liver should be performed due to data given in literature and its sensitivity of 100%. Because of the delayed detectability of cerebral manifestations, in cases of persisting suspicion even a previously normal MRI of the brain should be repeated. (orig.) [Deutsch] Untersuchung des Nutzens der MRT der Leber und des Gehirns bei klinisch auffaelligen haematologischen Patienten mit Fieber unbekannter Ursache. Material und Methoden: Es wurden 20 MRT der Leber (T{sub 2}-TSE, T{sub 2}-HASTE, T{sub 1}-FLASH{+-}Gd dynamisch) und 16 MRT des Gehirns (T{sub 2}-TSE, FLAIR, T{sub 1}-TSE{+-}Gd) zur Fokussuche bei Infektionsverdacht und Organhinweisen durchgefuehrt. Es erfolgte der Abgleich mit dem weiteren klinischen Verlauf. Ergebnisse: 11/20 MRT-Untersuchungen der Leber zeigten einen Herdbefund: Candidiasis (n=3), Mykobakteriose (n=2

  19. Muscle Cramps

    Science.gov (United States)

    ... Talk to your provider about the risks and benefits of medicines. How can I prevent muscle cramps? To prevent muscle cramps, you can Stretch your muscles, especially before exercising. If you often get leg cramps at night, ...

  20. Multiresidue screening method for detection of benzimidazoles and their metabolites in liver and muscle by high-performance liquid chromatography: method development and validation according to Commission Decision 2002/657/EC

    Directory of Open Access Journals (Sweden)

    Marilena Gili

    2014-02-01

    Full Text Available The use of veterinary drugs may cause the presence of residues in food of animal origin if appropriate withdrawal periods are not respected. A high-performance liquid chromatography (HPLC method has been developed for the simultaneous detection of 11 benzimidazole residues, including metabolites – albendazole, albendazole sulphoxide, albendazole sulphone, fenbendazole, fenbendazole sulphoxide (oxfendazole, fenbendazole sulphone, flubendazole, mebendazole, oxibendazole, thiabendazole, 5-hydroxythiabendazole – in bovine, ovine, equine, swine, rabbit and poultry liver and in bovine, swine and fish muscle. After extraction with a dicloromethane/acetonitrile solution (35/65 v/v containing 5% ammonium hydroxide, the solvent was evaporated to dryness, the residue was dissolved in HCl 0.1 M, defatted with hexane, purified on a strong cation exchange solid-phase extraction cartridge and analysed in HPLC with diode array and fluorescence detectors. The method was validated as screening qualitative method evaluating, according to Commission Decision 2002/657/EC criteria, specificity, CCb and b error at cut off level of 25 mg/kg and ruggedness.

  1. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  2. CT numbers of liver and spleen in normal children

    International Nuclear Information System (INIS)

    Kim, Young Kim

    2002-01-01

    To determine the mean liver CT numbers, and differences between liver and spleen, and liver and back muscle CT numbers in normal children, and to correlate the findings with sex and age. One hundred and five normal children aged 2-14 years underwent pre-contrast CT scanning. Mean CT numbers of the liver, spleen, and back muscles were calculated, as well as the differences in CT numbers between the liver and spleen (liver-spleen CT numbers), and between the liver-back muscle CT numbers were 70.22±6.51 HU, 53.28±3.57 HU, 17.13±6.57 HU, and 11.88±5.94 HU, respectively. Mean liver CT numbers and the difference between liver and back muscle CT numbers were not different by age. By sex, all the CT numbers did not vary according to age. The sex of a subject did not affect the CT number. The children's mean liver CT number was 70.22±6.51 HU and the difference between liver and spleen CT numbers was 17.13±6.57 HU. Younger children had higher liver CT and liver-spleen CT numbers than older children. No CT numbers varied according to sex

  3. Liver spots

    Science.gov (United States)

    ... skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun ...

  4. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

  5. Liver disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  6. Cytochemical demonstration of mercury deposits in trout liver and kidney following methyl mercury intoxication: differentiation of two mercury pools by selenium

    DEFF Research Database (Denmark)

    Baatrup, E; Danscher, G

    1988-01-01

    and the selected organs were determined by measuring the uptake of 203Hg-labeled MeHg. Spleen, liver, and kidney had the highest concentrations after both experimental periods, while the largest relative increases were found in brain, muscle, and kidney. The subcellular distribution of mercury accumulations...... was demonstrated cytochemically in liver and kidney using the silver enhancement method by which accumulations of mercury-sulfides and/or mercury-selenides are made visible for light and electron microscopy. When sections prepared from the liver and kidney from fish, injected with selenium 2 hr prior to being...... pronounced in the kidney. The HgSe pool, supposed to represent methyl mercury, was shown by the presence of silver deposits at new locations as well as by an increase in the amount of deposits within lysosomes. The new locations included (1) secretory-like vesicles and the bile canaliculi of the liver...

  7. Fatty infiltration of the liver: evaluation by proton spectroscopic imaging

    International Nuclear Information System (INIS)

    Heiken, J.P.; Lee, J.K.; Dixon, W.T.

    1985-01-01

    The reliability of proton spectroscopic imaging in evaluating fatty infiltration of the liver was investigated in 35 subjects (12 healthy volunteers and 23 patients with fatty livers). With this modified spin-echo technique, fatty liver could be separated from normal liver both visually and quantitatively. On the opposed image, normal liver had an intermediate signal intensity, greater than that of muscle, whereas fatty liver had a lower signal intensity, equal to or less than that of muscle. In normal livers, the lipid signal fraction was less than 10%, while in fatty livers it was greater than 10% and usually exceeded 20%. With this technique, nonuniform fatty infiltration of the liver can be differentiated from hepatic metastases, and the technique may prove useful in the differentiation of some hepatic disorders

  8. Development and validation of a new GC-MS method for the detection of tramadol, O-desmethyltramadol, 6-acetylmorphine and morphine in blood, brain, liver and kidney of Wistar rats treated with the combination of heroin and tramadol.

    Science.gov (United States)

    Mahdy, Tarek; El-Shihi, Taha H; Emara, Mostafa M; Chericoni, Silvio; Giusiani, Mario; Giorgi, Mario

    2012-10-01

    Heroin is one of the most dangerous abused drugs in the world. Tramadol is an additive recently found at high concentration levels in street heroin seizures in Egypt. This substance could affect the usual analytical method for the detection of heroin and metabolites, as well as the pharmacokinetic and disposition of single analytes. One shortfall regarding this issue is present in the literature. This study describes a validated, simple, sensitive and selective method to determine tramadol, O-desmethyltramadol, 6-acetylmorphine and free morphine in the blood, brain, liver and kidney of Wistar rats, intraperitoneally treated with a combination of heroin and tramadol (10 and 70 mg/kg, respectively) using liquid-liquid extraction and gas chromatography-mass spectrometry detection. The calibration curves of tramadol, O-desmethyltramadol and 6-acetylmorphine in blood were linear in the concentration range from 25-5,000 ng/mL and morphine was found in the concentration range 50-5,000 ng/mL. The analytes were detected in all tested matrices, except 6-acetylmorphine, which was not detected in liver. The highest concentrations of tramadol and O-desmethyltramadol were observed in kidney (22,9381 and 28,498 ng/g), while 6-acetylmorphine and morphine were found at the highest levels in brain (3,280 and 3,899 ng/g, respectively). The present method is simple, rapid and sensitive and can be used to study the pharmacokinetics, disposition and interaction of these drugs in several animal models.

  9. Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy?

    Directory of Open Access Journals (Sweden)

    Valeria Barresi

    2014-04-01

    Full Text Available Despite ongoing clinical trials, the efficacy of anti-angiogenic drugs for the treatment of brain metastases (BM is still questionable. The lower response rate to anti-angiogenic therapy in the presence of BM than in metastatic disease involving other sites suggests that BM may be insensitive to these drugs, although the biological reasons underlining this phenomenon are still to be clarified. With the aim of assessing whether the targets of anti-angiogenic therapies are actually present in BM, in the present study, we analyzed the microvessel density (MVD, a measure of neo-angiogenesis, and the vascular phenotype (mature vs. immature in the tumor tissue of a series of BM derived from different primary tumors. By using immunohistochemistry against endoglin, a specific marker for newly formed vessels, we found that neo-angiogenesis widely varies in BM depending on the site of the primary tumor, as well as on its histotype. According to our results, BM from lung cancer displayed the highest MVD counts, while those from renal carcinoma had the lowest. Then, among BM from lung cancer, those from large cell and adenocarcinoma histotypes had significantly higher MVD counts than those originating from squamous cell carcinoma (p = 0.0043; p = 0.0063. Of note, MVD counts were inversely correlated with the maturation index of the endoglin-stained vessels, reflected by the coverage of smooth muscle actin (SMA positive pericytes (r = −0.693; p < 0.0001. Accordingly, all the endoglin-positive vessels in BM from pulmonary squamous cell carcinoma and renal carcinoma, displayed a mature phenotype, while vessels with an immature phenotype were found in highly vascularized BM from pulmonary large cell and adenocarcinoma. The low MVD and mature phenotype observed in BM from some primary tumors may account for their low sensitivity to anti-angiogenic therapies. Although our findings need to be validated in correlative studies with a clinical response, this should

  10. Markers of liver function and inflammatory cytokines modulation by ...

    African Journals Online (AJOL)

    Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic ... and is associated with over nutrition and under activity, ... of these subjects with leptin reduced liver fat and liver enzyme ... tissue, muscle-released interleukin-6 inhibition of tumor.

  11. Fatty Liver

    International Nuclear Information System (INIS)

    Filippone, A.; Digiovandomenico, V.; Digiovandomenico, E.; Genovesi, N.; Bonomo, L.

    1991-01-01

    The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a 'skip area', in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of 'Skip area'. Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between broght liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical 'skip area', by demonstrating normal density - which suggests that CT can characterize normal tissue in atypical 'skip area'

  12. Ventilatory strategy during liver transplantation

    DEFF Research Database (Denmark)

    Sørensen, Henrik; Grocott, Hilary P; Niemann, Mads

    2014-01-01

    BACKGROUND: As measured by near infrared spectroscopy (NIRS), cerebral oxygenation (ScO2) may be reduced by hyperventilation in the anhepatic phase of liver transplantation surgery (LTx). Conversely, the brain may be subjected to hyperperfusion during reperfusion of the grafted liver. We investig......, this retrospective analysis suggests that attention to maintain a targeted EtCO2 would result in a more stable ScO2 during the operation....

  13. Edward F. Adolph distinguished lecture: muscle as an endocrine organ: IL-6 and other myokines

    DEFF Research Database (Denmark)

    Pedersen, Bente K

    2009-01-01

    Skeletal muscle is an endocrine organ that produces and releases myokines in response to contraction. Some myokines are likely to work in a hormone-like fashion, exerting specific endocrine effects on other organs such as the liver, the brain, and the fat. Other myokines will work locally via......, technological, and scholarly horizons. This finding represents a breakthrough within integrative physiology and contributes to our understanding of why regular exercise protects against a wide range of chronic diseases. Thus the myokine field provides a conceptual basis for the molecular mechanisms underlying...

  14. Brain glycogen in health and disease.

    Science.gov (United States)

    Duran, Jordi; Guinovart, Joan J

    2015-12-01

    Glycogen is present in the brain at much lower concentrations than in muscle or liver. However, by characterizing an animal depleted of brain glycogen, we have shown that the polysaccharide plays a key role in learning capacity and in activity-dependent changes in hippocampal synapse strength. Since glycogen is essentially found in astrocytes, the diverse roles proposed for this polysaccharide in the brain have been attributed exclusively to these cells. However, we have demonstrated that neurons have an active glycogen metabolism that contributes to tolerance to hypoxia. However, these cells can store only minute amounts of glycogen, since the progressive accumulation of this molecule leads to neuronal loss. Loss-of-function mutations in laforin and malin cause Lafora disease. This condition is characterized by the presence of high numbers of insoluble polyglucosan bodies, known as Lafora bodies, in neuronal cells. Our findings reveal that the accumulation of this aberrant glycogen accounts for the neurodegeneration and functional consequences, as well as the impaired autophagy, observed in models of this disease. Similarly glycogen synthase is responsible for the accumulation of corpora amylacea, which are polysaccharide-based aggregates present in the neurons of aged human brains. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism is important under stress conditions and that neuronal glycogen accumulation contributes to neurodegenerative diseases and to aging-related corpora amylacea formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. In vitro study of the biological activity of RNAs after incubation of hog liver, heart and brain tissue at room temperature

    DEFF Research Database (Denmark)

    Reichert, G H; Issinger, O G

    1985-01-01

    The biological activity of RNA, isolated from tissue which was incubated for 1, 3, or 6 hours at room temperature (simulation of post-mortem conditions), was preserved. However, the different organs used differ from each other. When liver is used, qualitative differences in the in vitro translati...... RNase inhibitors during thawing to reduce the loss of biological activity....

  16. Comparing Outcomes of Donation After Cardiac Death Versus Donation After Brain Death in Liver Transplant Recipients with Hepatitis C: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Malcolm Wells

    2014-01-01

    Full Text Available BACKGROUND: Liver transplantation (LT using organs donated after cardiac death (DCD is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV infection remains unclear due to the limited experience and number of publications addressing this issue.

  17. Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

    International Nuclear Information System (INIS)

    Shahbazian, F.M.

    1985-01-01

    Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of [ 14 C]valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements

  18. The Duchenne brain

    NARCIS (Netherlands)

    Doorenweerd, N.

    2017-01-01

    Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness caused by DMD gene mutations leading to absence of the full-length dystrophin protein in muscle. Multiple dystrophin isoforms are expressed in brain, but little is known about their function. DMD is associated with

  19. Liver Disease

    Science.gov (United States)

    ... and ridding your body of toxic substances. Liver disease can be inherited (genetic) or caused by a variety of factors that damage the ... that you can't stay still. Causes Liver disease has many ... or semen, contaminated food or water, or close contact with a person who is ...

  20. Liver scintigraphy

    International Nuclear Information System (INIS)

    Tateno, Yukio

    1996-01-01

    Liver scintigraphy can be classified into 3 major categories according to the properties of the radiopharmaceuticals used, i.e., methods using radiopharmaceuticals which are (1) incorporated by hepatocytes, (2) taken up by reticulo endothelial cells, and (3) distributed in the blood pool of the liver. Of these three categories, the liver scintigraphy of the present research falls into category 2. Radiopharmaceuticals which are taken up by endothelial cells include 198 Au colloids and 99m Tc-labelled colloids. Liver scintigraphy takes advantage of the property by which colloidal microparticles are phagocytosed by Kupffer cells, and reflect the distribution of endothelial cells and the intensity of their phagocytic capacity. This examination is indicated in the following situations: (i) when you suspect a localized intrahepatic lesion (tumour, abscess, cyst, etc.), (ii) when you want to follow the course of therapy of a localized lesion, (iii) when you suspect liver cirrhosis, (iv) when you want to know the severity of liver cirrhosis or hepatitis, (v) when there is hepatomegaly and you want to determine the morphology of the liver, (vi) differential diagnosis of upper abdominal masses, and (vii) when there are abnormalities of the right diaphragm and you want to know their relation to the liver

  1. Liver regeneration

    NARCIS (Netherlands)

    Chamuleau, R. A.; Bosman, D. K.

    1988-01-01

    Despite great advances in analysing hemodynamic, morphological and biochemical changes during the process of liver regeneration, the exact (patho)physiological mechanism is still unknown. A short survey of literature is given of the kinetics of liver regeneration and the significance of different

  2. The glycosylation status of the murine hepatitis coronavirus M protein affects the interferogenic capacity of the virus in vitro and its ability to replicate in the liver but not the brain

    International Nuclear Information System (INIS)

    Haan, Cornelis A.M. de; Wit, Marel de; Kuo, Lili; Montalto-Morrison, Cynthia; Haagmans, Bart L.; Weiss, Susan R.; Masters, Paul S.; Rottier, Peter J.M.

    2003-01-01

    The coronavirus M protein, the most abundant coronaviral envelope component, is invariably glycosylated, which provides the virion with a diffuse, hydrophilic cover on its outer surface. Remarkably, while the group 1 and group 3 coronaviruses all have M proteins with N-linked sugars, the M proteins of the group 2 coronaviruses [e.g., mouse hepatitis virus (MHV)] are O-glycosylated. The conservation of the N- and O-glycosylation motifs suggests that each of these types of carbohydrate modifications is beneficial to their respective virus. Since glycosylation of the M protein is not required for virus assembly, the oligosaccharides are likely to be involved in the virus-host interaction. In order to investigate the role of the M protein glycosylation in the host, two genetically modified MHVs were generated by using targeted RNA recombination. The recombinant viruses carried M proteins that were either N-glycosylated or not glycosylated at all, and these were compared with the parental, O-glycosylated, virus. The M protein glycosylation state did not influence the tissue culture growth characteristics of the recombinant viruses. However, it affected their interferogenic capacity as measured using fixed, virus-infected cells. Viruses containing M proteins with N-linked sugars induced type I interferons to higher levels than viruses carrying M proteins with O-linked sugars. MHV with unglycosylated M proteins appeared to be a poor interferon inducer. In mice, the recombinant viruses differed in their ability to replicate in the liver, but not in the brain, whereas their in vivo interferogenic capacity did not appear to be affected by their glycosylation status. Strikingly, their abilities to replicate in the liver correlated with their in vitro interferogenic capacity. This apparent correlation might be explained by the functioning of lectins, such as the mannose receptor, which are abundantly expressed in the liver but also play a role in the induction of interferon

  3. Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats.

    Science.gov (United States)

    Amin, Mohamed M; Arbid, Mahmoud S

    2017-02-01

    Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.

  4. Muscle Contraction.

    Science.gov (United States)

    Sweeney, H Lee; Hammers, David W

    2018-02-01

    SUMMARYMuscle cells are designed to generate force and movement. There are three types of mammalian muscles-skeletal, cardiac, and smooth. Skeletal muscles are attached to bones and move them relative to each other. Cardiac muscle comprises the heart, which pumps blood through the vasculature. Skeletal and cardiac muscles are known as striated muscles, because the filaments of actin and myosin that power their contraction are organized into repeating arrays, called sarcomeres, that have a striated microscopic appearance. Smooth muscle does not contain sarcomeres but uses the contraction of filaments of actin and myosin to constrict blood vessels and move the contents of hollow organs in the body. Here, we review the principal molecular organization of the three types of muscle and their contractile regulation through signaling mechanisms and discuss their major structural and functional similarities that hint at the possible evolutionary relationships between the cell types. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. Efficacy of liver parenchymal enhancement and liver volume to standard liver volume ratio on Gd-EOB-DTPA-enhanced MRI for estimation of liver function

    Energy Technology Data Exchange (ETDEWEB)

    Yoneyama, Tomohide; Fukukura, Yoshihiko; Kamimura, Kiyohisa; Takumi, Koji; Umanodan, Aya; Nakajo, Masayuki [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Radiology, Kagoshima City (Japan); Ueno, Shinichi [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Surgical Oncology and Digestive Surgery, Kagoshima City (Japan)

    2014-04-15

    We aimed to develop and assess the efficacy of a liver function index that combines liver enhancement and liver volume to standard liver volume (LV/SLV) ratio on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. In all, 111 patients underwent a Gd-EOB-DTPA-enhanced MRI, including T1 mapping, before and 20 min after Gd-EOB-DTPA administration. We calculated the following Gd-EOB-DTPA-enhanced MRI-based liver function indices: relative enhancement of the liver, corrected enhancement of the liver-to-spleen ratio, LSC{sub N}20, increase rate of the liver-to-muscle ratio, reduction rate of T1 relaxation time of the liver, ΔR1 of the liver and K{sub Hep}; the indices were multiplied by the LV/SLV ratio. We calculated the correlations between an indocyanine green (ICG) clearance and the Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio, by using Pearson correlation analysis. There were significant correlations between all Gd-EOB-DTPA-enhanced MRI-based liver function indices and ICG clearance (r = -0.354 to -0.574, P < 0.001). All Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio (r = -0.394 to -0.700, P < 0.001) were more strongly correlated with the ICG clearance than those without multiplication by the LV/SLV ratio. Gd-EOB-DTPA-enhanced MRI-based liver function indices that combine liver enhancement and the LV/SLV ratio may more reliably estimate liver function. (orig.)

  6. [Liver transplantation].

    Science.gov (United States)

    Pompili, Maurizio; Mirante, Vincenzo Giorgio; Rapaccini, Gian Ludovico; Gasbarrini, Giovanni

    2004-01-01

    Liver transplantation represents the first choice treatment for patients with fulminant acute hepatitis and for patients with chronic liver disease and advanced functional failure. Patients in the waiting list for liver transplantation are classified according to the severity of their clinical conditions (evaluated using staging systems mostly based on hematochemical parameters related to liver function). This classification, together with the blood group and the body size compatibility, remains the main criterion for organ allocation. The main indications for liver transplantation are cirrhosis (mainly HCV-, HBV- and alcohol-related) and hepatocellular carcinoma emerging in cirrhosis in adult patients, biliary atresia and some inborn errors of metabolism in pediatric patients. In adults the overall 5-year survival ranges between 60 and 70%, in both American and European series. Even better results have been reported for pediatric patients: in fact, the 5-year survival rate for children ranges between 70 and 80% in the main published series. In this study we evaluated the main medical problems correlated with liver transplantation such as immunosuppressive treatment, acute and chronic rejection, infectious complications, the recurrence of the liver disease leading to transplantation, and cardiovascular and metabolic complications.

  7. Benign Liver Tumors

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  8. Liver Function Tests

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  9. Progression of Liver Disease

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  10. Liver (Hepatocellular) Cancer Screening

    Science.gov (United States)

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  11. High-resolution respirometry of fine-needle muscle biopsies in pre-manifest Huntington's disease expansion mutation carriers shows normal mitochondrial respiratory function.

    Directory of Open Access Journals (Sweden)

    Eva Buck

    Full Text Available Alterations in mitochondrial respiration are an important hallmark of Huntington's disease (HD, one of the most common monogenetic causes of neurodegeneration. The ubiquitous expression of the disease causing mutant huntingtin gene raises the prospect that mitochondrial respiratory deficits can be detected in skeletal muscle. While this tissue is readily accessible in humans, transgenic animal models offer the opportunity to cross-validate findings and allow for comparisons across organs, including the brain. The integrated respiratory chain function of the human vastus lateralis muscle was measured by high-resolution respirometry (HRR in freshly taken fine-needle biopsies from seven pre-manifest HD expansion mutation carriers and nine controls. The respiratory parameters were unaffected. For comparison skeletal muscle isolated from HD knock-in mice (HdhQ111 as well as a broader spectrum of tissues including cortex, liver and heart muscle were examined by HRR. Significant changes of mitochondrial respiration in the HdhQ knock-in mouse model were restricted to the liver and the cortex. Mitochondrial mass as quantified by mitochondrial DNA copy number and citrate synthase activity was stable in murine HD-model tissue compared to control. mRNA levels of key enzymes were determined to characterize mitochondrial metabolic pathways in HdhQ mice. We demonstrated the feasibility to perform high-resolution respirometry measurements from small human HD muscle biopsies. Furthermore, we conclude that alterations in respiratory parameters of pre-manifest human muscle biopsies are rather limited and mirrored by a similar absence of marked alterations in HdhQ skeletal muscle. In contrast, the HdhQ111 murine cortex and liver did show respiratory alterations highlighting the tissue specific nature of mutant huntingtin effects on respiration.

  12. Basic models modeling resistance training: an update for basic scientists interested in study skeletal muscle hypertrophy.

    Science.gov (United States)

    Cholewa, Jason; Guimarães-Ferreira, Lucas; da Silva Teixeira, Tamiris; Naimo, Marshall Alan; Zhi, Xia; de Sá, Rafaele Bis Dal Ponte; Lodetti, Alice; Cardozo, Mayara Quadros; Zanchi, Nelo Eidy

    2014-09-01

    Human muscle hypertrophy brought about by voluntary exercise in laboratorial conditions is the most common way to study resistance exercise training, especially because of its reliability, stimulus control and easy application to resistance training exercise sessions at fitness centers. However, because of the complexity of blood factors and organs involved, invasive data is difficult to obtain in human exercise training studies due to the integration of several organs, including adipose tissue, liver, brain and skeletal muscle. In contrast, studying skeletal muscle remodeling in animal models are easier to perform as the organs can be easily obtained after euthanasia; however, not all models of resistance training in animals displays a robust capacity to hypertrophy the desired muscle. Moreover, some models of resistance training rely on voluntary effort, which complicates the results observed when animal models are employed since voluntary capacity is something theoretically impossible to measure in rodents. With this information in mind, we will review the modalities used to simulate resistance training in animals in order to present to investigators the benefits and risks of different animal models capable to provoke skeletal muscle hypertrophy. Our second objective is to help investigators analyze and select the experimental resistance training model that best promotes the research question and desired endpoints. © 2013 Wiley Periodicals, Inc.

  13. Enlarged Liver

    Science.gov (United States)

    ... of liver damage. Medicinal herbs. Certain herbs, including comfrey, ma huang and mistletoe, can increase your risk ... herbs to avoid include germander, chaparral, senna, mistletoe, comfrey, ma huang, valerian root, kava, celandine and green ...

  14. Biliary strictures and liver transplantation : clinical and biomedical aspects

    NARCIS (Netherlands)

    Sebib Korkmaz, Kerem

    2014-01-01

    The current thesis describes short and long term results of orthotopic liver transplantation (OLT) performed with livers from donation after brain death (DBD) and livers from donation after cardiac death (DCD) with an emphasis on biliary complications, especially nonanastomotic biliary strictures

  15. Image-derived input function in dynamic human PET/CT: methodology and validation with 11C-acetate and 18F-fluorothioheptadecanoic acid in muscle and 18F-fluorodeoxyglucose in brain

    International Nuclear Information System (INIS)

    Croteau, Etienne; Lavallee, Eric; Hubert, Laurent; Rousseau, Jacques A.; Lecomte, Roger; Labbe, Sebastien M.; Carpentier, Andre C.; Pifferi, Fabien; Cunnane, Stephen C.; Benard, Francois

    2010-01-01

    Despite current advances in PET/CT systems, blood sampling still remains the standard method to obtain the radiotracer input function for tracer kinetic modelling. The purpose of this study was to validate the use of image-derived input functions (IDIF) of the carotid and femoral arteries to measure the arterial input function (AIF) in PET imaging. The data were obtained from two different research studies, one using 18 F-FDG for brain imaging and the other using 11 C-acetate and 18 F-fluoro-6-thioheptadecanoic acid ( 18 F-FTHA) in femoral muscles. The method was validated with two phantom systems. First, a static phantom consisting of syringes of different diameters containing radioactivity was used to determine the recovery coefficient (RC) and spill-in factors. Second, a dynamic phantom built to model bolus injection and clearance of tracers was used to establish the correlation between blood sampling, AIF and IDIF. The RC was then applied to the femoral artery data from PET imaging studies with 11 C-acetate and 18 F-FTHA and to carotid artery data from brain imaging with 18 F-FDG. These IDIF data were then compared to actual AIFs from patients. With 11 C-acetate, the perfusion index in the femoral muscle was 0.34±0.18 min -1 when estimated from the actual time-activity blood curve, 0.29±0.15 min -1 when estimated from the corrected IDIF, and 0.66±0.41 min -1 when the IDIF data were not corrected for RC. A one-way repeated measures (ANOVA) and Tukey's test showed a statistically significant difference for the IDIF not corrected for RC (p 18 F-FTHA there was a strong correlation between Patlak slopes, the plasma to tissue transfer rate calculated using the true plasma radioactivity content and the corrected IDIF for the femoral muscles (vastus lateralis r=0.86, p=0.027; biceps femoris r=0.90, p=0.017). On the other hand, there was no correlation between the values derived using the AIF and those derived using the uncorrected IDIF. Finally, in the brain imaging

  16. Possible link between Hg and Cd accumulation in the brain of long-finned pilot whales (Globicephala melas)

    Energy Technology Data Exchange (ETDEWEB)

    Gajdosechova, Zuzana [Trace Element Speciation Laboratory, Department of Chemistry, Meston Walk, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom); Brownlow, Andrew [SAC Wildlife Unit, Inverness (United Kingdom); Cottin, Nicolas T.; Fernandes, Mariana [Trace Element Speciation Laboratory, Department of Chemistry, Meston Walk, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom); Read, Fiona L. [Oceanlab, University of Aberdeen, Main Street, Newburgh AB41 6AA (United Kingdom); Urgast, Dagmar S.; Raab, Andrea; Feldmann, Jörg; Krupp, Eva M. [Trace Element Speciation Laboratory, Department of Chemistry, Meston Walk, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom)

    2016-03-01

    The bioaccumulation of metals was investigated by analysis of liver, kidney, muscle and brain tissue of a pod of 21 long-finned pilot whales (Globicephala melas) of all ages stranded in Scotland, UK. The results are the first to report cadmium (Cd) passage through the blood–brain barrier of pilot whales and provide a comprehensive study of the long-term (up to 35 years) mammalian exposure to the environmental pollutants. Additionally, linear accumulation of mercury (Hg) was observed in all studied tissues, whereas for Cd this was only observed in the liver. Total Hg concentration above the upper neurochemical threshold was found in the sub-adult and adult brains and methylmercury (MeHg) of 2.2 mg/kg was found in the brain of one individual. Inter-elemental analysis showed significant positive correlations of Hg with selenium (Se) and Cd with Se in all studied tissues. Furthermore, differences in the elemental concentrations in the liver and brain tissues were found between juvenile, sub-adult and adult groups. The highest concentrations of manganese, iron, zinc, Se, Hg and MeHg were noted in the livers, whereas Cd predominantly accumulated in the kidneys. High concentrations of Hg and Cd in the tissues of pilot whales presented in this study reflect ever increasing toxic stress on marine mammals. - Highlights: • Trace elements were measured in a pod of 21 pilot whales stranded in Scotland. • Bioaccumulation of mercury and methyl mercury was found in all studied tissues. • Cadmium age related accumulation was observed in the liver and brain tissues. • Cadmium-selenium correlations suggest formation of cadmium-selenium complexes.

  17. Possible link between Hg and Cd accumulation in the brain of long-finned pilot whales (Globicephala melas)

    International Nuclear Information System (INIS)

    Gajdosechova, Zuzana; Brownlow, Andrew; Cottin, Nicolas T.; Fernandes, Mariana; Read, Fiona L.; Urgast, Dagmar S.; Raab, Andrea; Feldmann, Jörg; Krupp, Eva M.

    2016-01-01

    The bioaccumulation of metals was investigated by analysis of liver, kidney, muscle and brain tissue of a pod of 21 long-finned pilot whales (Globicephala melas) of all ages stranded in Scotland, UK. The results are the first to report cadmium (Cd) passage through the blood–brain barrier of pilot whales and provide a comprehensive study of the long-term (up to 35 years) mammalian exposure to the environmental pollutants. Additionally, linear accumulation of mercury (Hg) was observed in all studied tissues, whereas for Cd this was only observed in the liver. Total Hg concentration above the upper neurochemical threshold was found in the sub-adult and adult brains and methylmercury (MeHg) of 2.2 mg/kg was found in the brain of one individual. Inter-elemental analysis showed significant positive correlations of Hg with selenium (Se) and Cd with Se in all studied tissues. Furthermore, differences in the elemental concentrations in the liver and brain tissues were found between juvenile, sub-adult and adult groups. The highest concentrations of manganese, iron, zinc, Se, Hg and MeHg were noted in the livers, whereas Cd predominantly accumulated in the kidneys. High concentrations of Hg and Cd in the tissues of pilot whales presented in this study reflect ever increasing toxic stress on marine mammals. - Highlights: • Trace elements were measured in a pod of 21 pilot whales stranded in Scotland. • Bioaccumulation of mercury and methyl mercury was found in all studied tissues. • Cadmium age related accumulation was observed in the liver and brain tissues. • Cadmium-selenium correlations suggest formation of cadmium-selenium complexes.

  18. Robust Brain-Computer Interfaces

    NARCIS (Netherlands)

    Reuderink, B.

    2011-01-01

    A brain-computer interface (BCI) enables direct communication from the brain to devices, bypassing the traditional pathway of peripheral nerves and muscles. Current BCIs aimed at patients require that the user invests weeks, or even months, to learn the skill to intentionally modify their brain

  19. Nutritional Therapy in Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Ahmed Hammad

    2017-10-01

    Full Text Available Protein-energy malnourishment is commonly encountered in patients with end-stage liver disease who undergo liver transplantation. Malnutrition may further increase morbidity, mortality and costs in the post-transplantation setting. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognized. The metabolic abnormalities induced by liver failure render the conventional assessment of nutritional status to be challenging. Preoperative loss of skeletal muscle mass, namely, sarcopenia, has a significant detrimental impact on post-transplant outcomes. It is essential to provide sufficient nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the needed energy intake. Herein, the latest currently employed perioperative nutritional interventions in liver transplant recipients are thoroughly illustrated including synbiotics, micronutrients, branched-chain amino acid supplementation, immunonutrition formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary counselling, exercise and rehabilitation.

  20. Your Muscles

    Science.gov (United States)

    ... and you need to throw up. The muscles push the food back out of the stomach so it comes up ... body the power it needs to lift and push things. Muscles in your neck and the top part of your back aren't as large, but they are capable ...

  1. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    International Nuclear Information System (INIS)

    Klin, Yael; Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram; Teichberg, Vivian I.

    2010-01-01

    Research highlights: → Blood glutamate has a half-life time of 2-3 min. → Blood glutamate is submitted to rapid decarboxylation. → Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. → The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1- 14 C] Glutamic acid (L-[1- 14 C] Glu), L-[G- 3 H] Glutamic acid (L-[G- 3 H] Glu) or D-[2,3- 3 H] Aspartic acid (D-[2,3- 3 H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1- 14 C] Glu and L-[G- 3 H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3- 3 H] Asp. L-[1- 14 C] Glu was subjected in blood to a rapid decarboxylation with the loss of 14 CO 2 . The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U- 14 C] Glu or D-[2,3- 3 H] Asp radioactivity capture. L-[U- 14 C] Glu and D-[2,3- 3 H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues, mainly in non-metabolized form. The liver plays a central role in glutamate metabolism

  2. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Klin, Yael [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel); Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram [The Division of Anesthesiology, Soroka Medical Center and Ben Gurion University of the Negev, Beer-Sheva (Israel); Teichberg, Vivian I., E-mail: Vivian.teichberg@weizmann.ac.il [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel)

    2010-09-03

    Research highlights: {yields} Blood glutamate has a half-life time of 2-3 min. {yields} Blood glutamate is submitted to rapid decarboxylation. {yields} Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. {yields} The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1-{sup 14}C] Glutamic acid (L-[1-{sup 14}C] Glu), L-[G-{sup 3}H] Glutamic acid (L-[G-{sup 3}H] Glu) or D-[2,3-{sup 3}H] Aspartic acid (D-[2,3-{sup 3}H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1-{sup 14}C] Glu and L-[G-{sup 3}H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3-{sup 3}H] Asp. L-[1-{sup 14}C] Glu was subjected in blood to a rapid decarboxylation with the loss of {sup 14}CO{sub 2}. The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U-{sup 14}C] Glu or D-[2,3-{sup 3}H] Asp radioactivity capture. L-[U-{sup 14}C] Glu and D-[2,3-{sup 3}H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues

  3. Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice.

    Science.gov (United States)

    de Sousa Rodrigues, Maria Elizabeth; Bekhbat, Mandakh; Houser, Madelyn C; Chang, Jianjun; Walker, Douglas I; Jones, Dean P; Oller do Nascimento, Claudia M P; Barnum, Christopher J; Tansey, Malú G

    2017-01-01

    The mechanisms underlying the association between chronic psychological stress, development of metabolic syndrome (MetS), and behavioral impairment in obesity are poorly understood. The aim of the present study was to assess the effects of mild chronic psychological stress on metabolic, inflammatory, and behavioral profiles in a mouse model of diet-induced obesity. We hypothesized that (1) high-fat high-fructose diet (HFHF) and psychological stress would synergize to mediate the impact of inflammation on the central nervous system in the presence of behavioral dysfunction, and that (2) HFHF and stress interactions would impact insulin and lipid metabolism. C57Bl/6 male mice underwent a combination of HFHF and two weeks of chronic psychological stress. MetS-related conditions were assessed using untargeted plasma metabolomics, and structural and immune changes in the gut and liver were evaluated. Inflammation was measured in plasma, liver, gut, and brain. Our results show a complex interplay of diet and stress on gut alterations, energetic homeostasis, lipid metabolism, and plasma insulin levels. Psychological stress and HFHF diet promoted changes in intestinal tight junctions proteins and increases in insulin resistance and plasma cholesterol, and impacted the RNA expression of inflammatory factors in the hippocampus. Stress promoted an adaptive anti-inflammatory profile in the hippocampus that was abolished by diet treatment. HFHF increased hippocampal and hepatic Lcn2 mRNA expression as well as LCN2 plasma levels. Behavioral changes were associated with HFHF and stress. Collectively, these results suggest that diet and stress as pervasive factors exacerbate MetS-related conditions through an inflammatory mechanism that ultimately can impact behavior. This rodent model may prove useful for identification of possible biomarkers and therapeutic targets to treat metabolic syndrome and mood disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. NMR of 19F emulsions: methodological developments and application to evaluation of oxi-metry and dynamic biodistribution in the liver and spleen and to detection of tumor angiogenesis in the rodent brain

    International Nuclear Information System (INIS)

    Giraudeau, C.

    2012-01-01

    This study aimed at developing a method for detection of brain tumors at 7 tesla thanks to 19 F MRI contrast agents. We particularly assessed the potential of this method to highlight tumor angiogenesis with RGD-functionalized contrast agents targeting αvβ3integrin, a bio-marker over-expressed at the surface of new capillary blood vessels. Owing to low local concentrations in contrast agent, the first step consisted in optimizing a multi spin echo sequence dedicated to a well-known biocompatible per-fluorocarbon, perfluoro-octylbromide (PFOB). We show that careful adjustment of sequence parameters allows cancellation of J-modulation and T2 enhancement, and yields an excellent sensitivity in vitro. Our sequence was then tested for oxygenation measurements in the mouse liver and spleen after injection of a PFOB emulsion. The results demonstrate very good accuracy of the measurements after one single infusion of emulsion. We also perform a dynamic biodistribution study in order to monitor emulsion nano-particle uptake in the liver and spleen. Moreover, we show that stealth of emulsions grafted with different quantities of polyethylene glycol (PEG) can be assessed by fitting experimental data with a pharmacokinetic empirical model. Our sequence was finally used to visualize αvβ3-targeted nano-particles in a U87 glioblastoma mouse model. Concentrations found in tumors after injection of an RGD-functionalized emulsion and a control emulsion are compared. Concentrations are found to be significantly higher with the RGD emulsion than with the control emulsion, suggesting specific binding of functionalized nano-particles with αvβ3 integrin. The last part is dedicated to a new diffusion-weighted 19 F NMR spectroscopy sequence. This method aims at suppressing vascular signal coming from circulating PFOB nano-particles in order to evaluate signal coming from bound nano-particles only. (author) [fr

  5. Autoimmune paediatric liver disease.

    Science.gov (United States)

    Mieli-Vergani, Giorgina; Vergani, Diego

    2008-06-07

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

  6. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

    Science.gov (United States)

    Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

  7. Association between muscle mass and a single measurement of ...

    African Journals Online (AJOL)

    cause mortality significantly. It is strongly associated with the risk of heart attack, coronary artery disease, cardiovascular disease, stroke and liver disease. The relationship between muscle mass and a diagnosis of hypertension in a sample of ...

  8. Amoebic liver

    African Journals Online (AJOL)

    lymphadenopathy were noted. The right-sided pleural effusion with relaxation atelectasis was also con- firmed (Fig. 4). The diagnosis of pos- sible amoebic liver abscess complicat- ed by rupture to the gallbladder was made at that stage. Ultrasound-guided abscess drainage was done and approximately 300 ml of pus was.

  9. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic (Liver) ... kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a blood ...

  10. American Liver Foundation

    Science.gov (United States)

    ... Cirrhosis Clinical Trials Galactosemia Gilbert Syndrome Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Hepatocellular Carcinoma Lysosomal Acid Lipase Deficiency(LALD) Intrahepatic Cholestasis of Pregnancy (ICP) Liver Biopsy Liver Cancer Liver Cysts Liver Function Tests ...

  11. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  12. Muscle cramps

    Science.gov (United States)

    ... the lower leg/calf Back of the thigh (hamstrings) Front of the thigh (quadriceps) Cramps in the ... Names Cramps - muscle Images Chest stretch Groin stretch Hamstring stretch Hip stretch Thigh stretch Triceps stretch References ...

  13. Muscle atrophy

    Science.gov (United States)

    ... People who cannot actively move one or more joints can do exercises using braces or splints . When ... A.M. Editorial team. Muscle Disorders Read more Neuromuscular Disorders Read more NIH MedlinePlus Magazine Read more ...