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

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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

Functional evaluation of artificial skeletal muscle tissue constructs fabricated by a magnetic force-based tissue engineering technique.

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Yamamoto, Yasunori; Ito, Akira; Fujita, Hideaki; Nagamori, Eiji; Kawabe, Yoshinori; Kamihira, Masamichi

2011-01-01

Skeletal muscle tissue engineering is currently applied in a variety of research fields, including regenerative medicine, drug screening, and bioactuator development, all of which require the fabrication of biomimic and functional skeletal muscle tissues. In the present study, magnetite cationic liposomes were used to magnetically label C2C12 myoblast cells for the construction of three-dimensional artificial skeletal muscle tissues by an applied magnetic force. Skeletal muscle functions, such as biochemical and contractile properties, were evaluated for the artificial tissue constructs. Histological studies revealed that elongated and multinucleated myotubes were observed within the tissue. Expression of muscle-specific markers, such as myogenin, myosin heavy chain and tropomyosin, were detected in the tissue constructs by western blot analysis. Further, creatine kinase activity increased during differentiation. In response to electric pulses, the artificial tissue constructs contracted to generate a physical force (the maximum twitch force, 33.2 μN [1.06 mN/mm2]). Rheobase and chronaxie of the tissue were determined as 4.45 V and 0.72 ms, respectively. These results indicate that the artificial skeletal muscle tissue constructs fabricated in this study were physiologically functional and the data obtained for the evaluation of their functional properties may provide useful information for future skeletal muscle tissue engineering studies.

Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses.

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Aspenström-Fagerlund, Bitte; Nordkvist, Erik; Törnkvist, Anna; Wallgren, Per; Hoogenboom, Ron; Berendsen, Bjorn; Granelli, Kristina

2016-09-01

Toxic effects of chloramphenicol in humans caused the ban for its use in food-producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 μg kg(-1) for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 μg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine.

Direct plasma interaction with living tissue

Science.gov (United States)

Fridman, Gregory

For some time, plasma has been used in medicine to cauterize or cut tissue using heat and mechanical energy. In the recent decade, some researchers around the world have started to investigate how gas jets that pass through thermal plasma can be employed in medicine. This thesis presents the first investigation of biomedical uses of non-thermal plasma discharge which comes in direct contact with living tissue. It is demonstrated that the direct application of non-thermal plasma in air can cause rapid deactivation of bacteria on surfaces of tissues without causing any visible tissue damage. Medical need for such a device is discussed. Construction and operation of various types of non-thermal plasma power supplies and many types of treatment electrodes are presented as well. Application of this plasma to living organisms is shown to be safe from both the electrical perspective and from the biological perspective. Biological safety is revealed through a series of differential skin toxicity trials on human cadaver tissue, live hairless mouse skin tissue, live pig skin tissue, and finally in an open wound model on pigs. Direct non-thermal plasma in air is shown to deactivate bacteria about 100 times faster than indirect application using jets. A series of experiments reveal that this effectiveness is due to the ability of direct discharge to bring charges to tissue surfaces. It is demonstrated that neither ultraviolet (UV) radiation nor neutral active species such as hydroxyl radicals or ozone produced in plasma are responsible for the main effect on bacteria. Although much additional work remains on establishing detailed mechanism by which charges from plasma achieve this effect, the work carried out in this thesis clearly demonstrates that direct application of non-thermal plasma in air can be a very useful tool in medicine.

Stem Cells for Skeletal Muscle Tissue Engineering.

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Pantelic, Molly N; Larkin, Lisa M

2018-04-19

Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML. Satellite cells are the native precursors to skeletal muscle tissue, and are thus the most commonly studied starting source for SMTE. However, satellite cells are difficult to isolate and purify, and it is presently unknown whether they would be a practical source in clinical SMTE applications. Alternative myogenic stem cells, including adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells, umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells, each have myogenic potential and have been identified as possible starting sources for SMTE, although they have yet to be studied in detail for this purpose. These alternative stem cell varieties offer unique advantages and disadvantages that are worth exploring further to advance the SMTE field toward highly functional, safe, and practical VML treatments. The following review summarizes the current state of satellite cell-based SMTE, details the properties and practical advantages of alternative myogenic stem cells, and offers guidance to tissue engineers on how alternative myogenic stem cells can be incorporated into SMTE research.

Characterisation of connective tissue from the hypertrophic skeletal muscle of myostatin null mice.

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Elashry, Mohamed I; Collins-Hooper, Henry; Vaiyapuri, Sakthivel; Patel, Ketan

2012-06-01

Myostatin is a potent inhibitor of muscle development. Genetic deletion of myostatin in mice results in muscle mass increase, with muscles often weighing three times their normal values. Contracting muscle transfers tension to skeletal elements through an elaborate connective tissue network. Therefore, the connective tissue of skeletal muscle is an integral component of the contractile apparatus. Here we examine the connective tissue architecture in myostatin null muscle. We show that the hypertrophic muscle has decreased connective tissue content compared with wild-type muscle. Secondly, we show that the hypertrophic muscle fails to show the normal increase in muscle connective tissue content during ageing. Therefore, genetic deletion of myostatin results in an increase in contractile elements but a decrease in connective tissue content. We propose a model based on the contractile profile of muscle fibres that reconciles this apparent incompatible tissue composition phenotype. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Assessing reproductive status in elasmobranch fishes using steroid hormones extracted from skeletal muscle tissue

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Prohaska, Bianca K.; Tsang, Paul C. W.; Driggers, William B.; Hoffmayer, Eric R.; Wheeler, Carolyn R.; Brown, A. Christine; Sulikowski, James A.

2013-01-01

Elasmobranch fishes (sharks, skates, and rays) are particularly susceptible to anthropogenic threats, making a thorough understanding of their life history characteristics essential for proper management. Historically, elasmobranch reproductive data have been collected by lethal sampling, an approach that is problematic for threatened and endangered species. However, recent studies have demonstrated that non-lethal approaches can be as effective as lethal ones for assessment of the reproductive status of an animal. For example, plasma has been used to examine concentrations of steroid hormones. Additionally, skeletal muscle tissue, which can be obtained non-lethally and with minimal stress, can also be used to quantify concentrations of steroid hormones. Skeletal muscle progesterone, testosterone, and estradiol concentrations were determined to be statistically significant indicators of reproductive status in the oviparous Leucoraja erinacea, the yolk-dependent viviparous Squalus acanthias, and the yolk-sac placental viviparous Rhizoprionodon terraenovae. The results of the present study demonstrate that steroid hormones present in non-lethally harvested skeletal muscle tissue can be used as reliable indicators of reproductive status in elasmobranchs. PMID:27293612

The essence of biophysical cues in skeletal muscle tissue engineering

NARCIS (Netherlands)

Langelaan, M.L.P.

2010-01-01

Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications. Evidently, tissue engineered skeletal muscle can be used in the field of regenerative medicine to repair muscular defects or dystrophies. Engineered skeletal muscle constructs can also be used as a

Mechanical stimulation improves tissue-engineered human skeletal muscle

Science.gov (United States)

Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

2002-01-01

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

Directory of Open Access Journals (Sweden)

Darimont Christian

2004-08-01

Full Text Available Abstract Background Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114 could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Methods Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. Results In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG and diacylglycerol (DAG accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. Conclusions These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.

Dietary copper in excess of nutritional requirement reduces plasma and breast muscle cholesterol of chickens.

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Bakalli, R I; Pesti, G M; Ragland, W L; Konjufca, V

1995-02-01

Male commercial broiler strain chickens were fed from hatching to 42 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 250 mg copper/kg diet from cupric sulfate pentahydrate (for 35 or 42 d). Hypocholesterolemia (11.8% reduction) and decreased breast muscle cholesterol (20.4% reduction) were observed in copper-supplemented birds. There was a slight increase (P > .05) in breast muscle copper (14.5%), and all levels were very low (copper for 42 vs 35 d resulted in lower levels of cholesterol in the plasma (12.9 vs 10.8% reduction) and breast muscle (24.6 vs 16.2% reduction). Very similar results were found in two additional experiments in which hypocholesterolemia and reduced breast muscle cholesterol were associated with reduced plasma triglycerides and blood reduced glutathione. It is well known that hypercholesterolemia is a symptom of dietary copper deficiency. The data presented here indicate that blood and breast muscle cholesterol are inversely related to dietary copper in excess of the dietary requirement for maximal growth. The cholesterol content of the edible muscle tissue of broiler chickens can be reduced by approximately 25% after feeding a supranormal level of copper for 42 d without altering the growth of the chickens or substantially increasing the copper content of the edible meat.

Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues.

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Nassari, Sonya; Duprez, Delphine; Fournier-Thibault, Claire

2017-01-01

Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult.

Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications.

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Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu; Khademhosseini, Ali

2014-10-01

Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.

Function of skeletal muscle tissue formed after myoblast transplantation into irradiated mouse muscles.

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Wernig, A; Zweyer, M; Irintchev, A

2000-01-15

1. Pretreatment of muscles with ionising radiation enhances tissue formation by transplanted myoblasts but little is known about the effects on muscle function. We implanted myoblasts from an expanded, male-donor-derived, culture (i28) into X-ray irradiated (16 Gy) or irradiated and damaged soleus muscles of female syngeneic mice (Balb/c). Three to 6 months later the isometric contractile properties of the muscles were studied in vitro, and donor nuclei were visualised in muscle sections with a Y chromosome-specific DNA probe. 2. Irradiated sham-injected muscles had smaller masses than untreated solei and produced less twitch and tetanic force (all by about 18 %). Injection of 106 myoblasts abolished these deficiencies and innervation appeared normal. 3. Cryodamage of irradiated solei produced muscle remnants with few (1-50) or no fibres. Additional myoblast implantation led to formation of large muscles (25 % above normal) containing numerous small-diameter fibres. Upon direct electrical stimulation, these muscles produced considerable twitch (53 % of normal) and tetanic forces (35 % of normal) but innervation was insufficient as indicated by weak nerve-evoked contractions and elevated ACh sensitivity. 4. In control experiments on irradiated muscles, reinnervation was found to be less complete after botulinum toxin paralysis than after nerve crush indicating that proliferative arrest of irradiated Schwann cells may account for the observed innervation deficits. 5. Irradiation appears to be an effective pretreatment for improving myoblast transplantation. The injected cells can even produce organised contractile tissue replacing whole muscle. However, impaired nerve regeneration limits the functional performance of the new muscle.

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...

The suprachiasmatic nucleus drives day-night variations in postprandial triglyceride uptake into skeletal muscle and brown adipose tissue.

Science.gov (United States)

Moran-Ramos, Sofía; Guerrero-Vargas, Natali N; Mendez-Hernandez, Rebeca; Basualdo, Maria Del Carmen; Escobar, Carolina; Buijs, Ruud M

2017-12-01

What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression

Muscle Activity Adaptations to Spinal Tissue Creep in the Presence of Muscle Fatigue

Science.gov (United States)

Nougarou, François

2016-01-01

Aim The aim of this study was to identify adaptations in muscle activity distribution to spinal tissue creep in presence of muscle fatigue. Methods Twenty-three healthy participants performed a fatigue task before and after 30 minutes of passive spinal tissue deformation in flexion. Right and left erector spinae activity was recorded using large-arrays surface electromyography (EMG). To characterize muscle activity distribution, dispersion was used. During the fatigue task, EMG amplitude root mean square (RMS), median frequency and dispersion in x- and y-axis were compared before and after spinal creep. Results Important fatigue-related changes in EMG median frequency were observed during muscle fatigue. Median frequency values showed a significant main creep effect, with lower median frequency values on the left side under the creep condition (p≤0.0001). A significant main creep effect on RMS values was also observed as RMS values were higher after creep deformation on the right side (p = 0.014); a similar tendency, although not significant, was observed on the left side (p = 0.06). A significant creep effects for x-axis dispersion values was observed, with higher dispersion values following the deformation protocol on the left side (p≤0.001). Regarding y-axis dispersion values, a significant creep x fatigue interaction effect was observed on the left side (p = 0.016); a similar tendency, although not significant, was observed on the right side (p = 0.08). Conclusion Combined muscle fatigue and creep deformation of spinal tissues led to changes in muscle activity amplitude, frequency domain and distribution. PMID:26866911

Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy: Molecular and Morphological Evidence.

Science.gov (United States)

Hodges, Paul W; James, Gregory; Blomster, Linda; Hall, Leanne; Schmid, Annina; Shu, Cindy; Little, Chris; Melrose, James

2015-07-15

Longitudinal case-controlled animal study. To investigate putative cellular mechanisms to explain structural changes in muscle and adipose and connective tissues of the back muscles after intervertebral disc (IVD) injury. Structural back muscle changes are ubiquitous with back pain/injury and considered relevant for outcome, but their exact nature, time course, and cellular mechanisms remain elusive. We used an animal model that produces phenotypic back muscle changes after IVD injury to study these issues at the cellular/molecular level. Multifidus muscle was harvested from both sides of the spine at L1-L2 and L3-L4 IVDs in 27 castrated male sheep at 3 (n = 10) or 6 (n = 17) months after a surgical anterolateral IVD injury at both levels. Ten control sheep underwent no surgery (3 mo, n = 4; 6 mo, n = 6). Tissue was harvested at L4 for histological analysis of cross-sectional area of muscle and adipose and connective tissue (whole muscle), plus immunohistochemistry to identify proportion and cross-sectional area of individual muscle fiber types in the deepest fascicle. Quantitative polymerase chain reaction measured gene expression of typical cytokines/signaling molecules at L2. Contrary to predictions, there was no multifidus muscle atrophy (whole muscle or individual fiber). There was increased adipose and connective tissue (fibrotic proliferation) cross-sectional area and slow-to-fast muscle fiber transition at 6 but not 3 months. Within the multifidus muscle, increases in the expression of several cytokines (tumor necrosis factor α and interleukin-1β) and molecules that signal trophic/atrophic processes for the 3 tissue types (e.g., growth factor pathway [IGF-1, PI3k, Akt1, mTOR], potent tissue modifiers [calcineurin, PCG-1α, and myostatin]) were present. This study provides cellular evidence that refutes the presence of multifidus muscle atrophy accompanying IVD degeneration at this intermediate time point. Instead, adipose/connective tissue increased in

How to assess the plasma delivery of RONS into tissue fluid and tissue

Science.gov (United States)

Oh, Jun-Seok; Szili, Endre J.; Gaur, Nishtha; Hong, Sung-Ha; Furuta, Hiroshi; Kurita, Hirofumi; Mizuno, Akira; Hatta, Akimitsu; Short, Robert D.

2016-08-01

The efficacy of helium (He) and argon (Ar) plasma jets are being investigated for different healthcare applications including wound and cancer therapy, sterilisation and surface disinfections. Current research points to a potential link between the generation of reactive oxygen and nitrogen species (RONS) and outcomes in a range of biological and medical applications. As new data accrue, further strengthening this link, it becomes important to understand the controlled delivery of RONS into solutions, tissue fluids and tissues. This paper investigates the use of He and Ar plasma jets to deliver three RONS (hydrogen peroxide—H2O2, nitrite—\\text{NO}2- and nitrate—\\text{NO}3- ) and molecular oxygen (O2) directly into deionised (DI) water, or indirectly into DI water through an agarose target. The DI water is used in place of tissue fluid and the agarose target serves as a surrogate of tissue. Direct plasma jet treatments deliver more RONS and O2 than the through-agarose treatments for equivalent treatments times. The former only deliver RONS whilst the plasma jets are ignited; the latter continues to deliver RONS into the DI water long after the plasmas are extinguished. The He plasma jet is more effective at delivering H2O2 and \\text{NO}2- directly into DI water, but the Ar plasma jet is more effective at nitrating the DI water in both direct and through-agarose treatments. DI water directly treated with the plasma jets is deoxygenated, with the He plasma jet purging more O2 than the Ar plasma jet. This effect is known as ‘sparging’. In contrast, for through-agarose treatments both jets oxygenated the DI water. These results indicate that in the context of direct and indirect plasma jet treatments of real tissue fluids and tissue, the choice of process gas (He or Ar) could have a profound effect on the concentrations of RONS and O2. Irrespective of operating gas, sparging of tissue fluid (in an open wound) for long prolonged periods during direct plasma

Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease.

Science.gov (United States)

Wens, Stephan C A; Schaaf, Gerben J; Michels, Michelle; Kruijshaar, Michelle E; van Gestel, Tom J M; In 't Groen, Stijn; Pijnenburg, Joon; Dekkers, Dick H W; Demmers, Jeroen A A; Verdijk, Lex B; Brusse, Esther; van Schaik, Ron H N; van der Ploeg, Ans T; van Doorn, Pieter A; Pijnappel, W W M Pim

2016-02-01

Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury. In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values normal in all patients, whereas CK-myocardial band levels were increased in 59% of patients. cTnT levels correlated with CK levels in all 3 subgroups (Pmass index measured with echocardiography was normal in all the 3 subgroups. cTnT mRNA expression in skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue. Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions. © 2016 American Heart Association, Inc.

Three-Dimensional Culture Model of Skeletal Muscle Tissue with Atrophy Induced by Dexamethasone.

Science.gov (United States)

Shimizu, Kazunori; Genma, Riho; Gotou, Yuuki; Nagasaka, Sumire; Honda, Hiroyuki

2017-06-15

Drug screening systems for muscle atrophy based on the contractile force of cultured skeletal muscle tissues are required for the development of preventive or therapeutic drugs for atrophy. This study aims to develop a muscle atrophy model by inducing atrophy in normal muscle tissues constructed on microdevices capable of measuring the contractile force and to verify if this model is suitable for drug screening using the contractile force as an index. Tissue engineered skeletal muscles containing striated myotubes were prepared on the microdevices for the study. The addition of 100 µM dexamethasone (Dex), which is used as a muscle atrophy inducer, for 24 h reduced the contractile force significantly. An increase in the expression of Atrogin-1 and MuRF-1 in the tissues treated with Dex was established. A decrease in the number of striated myotubes was also observed in the tissues treated with Dex. Treatment with 8 ng/mL Insulin-like Growth Factor (IGF-I) for 24 h significantly increased the contractile force of the Dex-induced atrophic tissues. The same treatment, though, had no impact on the force of the normal tissues. Thus, it is envisaged that the atrophic skeletal muscle tissues induced by Dex can be used for drug screening against atrophy.

The role of glucose, insulin and NEFA in regulating tissue triglyceride accumulation: Substrate cooperation in adipose tissue versus substrate competition in skeletal muscle.

Science.gov (United States)

Guzzardi, M A; Hodson, L; Guiducci, L; La Rosa, F; Salvadori, P A; Burchielli, S; Iozzo, P

2017-11-01

Metabolic factors initiating adipose tissue expansion and ectopic triglyceride accumulation are not completely understood. We aimed to investigate the independent role of circulating glucose, NEFA and insulin on glucose and NEFA uptake, and lipogenesis in skeletal muscle and subcutaneous adipose tissue (SCAT). Twenty-two pigs were stratified according to four protocols: 1) and 2) low NEFA + high insulin ± high glucose (hyperinsulinaemia-hyperglycaemia or hyperinsulinaemia-euglycaemia), 3) high NEFA + low insulin (fasting), 4) low NEFA + low insulin (nicotinic acid). Positron emission tomography with [ 18 F]fluoro-2-deoxyglucose and [ 11 C]acetate, was combined with [ 14 C]acetate and [U- 13 C]palmitate enrichment techniques to assess glucose and lipid metabolism. Hyperinsulinaemia increased glucose extraction, whilst hyperglycaemia enhanced glucose uptake in skeletal muscle and SCAT. In SCAT, during hyperglycaemia, elevated glucose uptake was accompanied by greater [U- 13 C]palmitate-TG enrichment compared to the other groups, and by a 39% increase in de novo lipogenesis (DNL) compared to baseline, consistent with a 70% increment in plasma lipogenic index. Conversely, in skeletal muscle, [U- 13 C]palmitate-TG enrichment was higher after prolonged fasting. Our data show the necessary role of hyperglycaemia-hyperinsulinaemia vs euglycaemia-hyperinsulinaemia in promoting expansion of TG stores in SCAT, by the consensual elevation in plasma NEFA and glucose uptake and DNL. In contrast, skeletal muscle NEFA uptake for TG synthesis is primarily driven by circulating NEFA levels. These results suggest that a) prolonged fasting or dietary regimens enhancing lipolysis might promote muscle steatosis, and b) the control of glucose levels, in association with adequate energy balance, might contribute to weight loss. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and

Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury.

Science.gov (United States)

Mackey, Abigail L; Kjaer, Michael

2017-03-01

Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibers as they undergo necrosis, followed closely by satellite cell-mediated myogenesis, have been mapped in detail. Much less is known about the adaptation throughout this process of both the connective tissue structures surrounding the myofibers and the fibroblasts, the cells responsible for synthesizing this connective tissue. However, the few studies investigating muscle connective tissue remodeling demonstrate a strong response that appears to be sustained for a long time after the major myofiber responses have subsided. While the use of electrical stimulation to induce eccentric contractions vs. voluntary eccentric contractions appears to lead to a greater extent of myofiber necrosis and regenerative response, this difference is not apparent when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning against this, however, is the association between muscle matrix protein remodeling and protection against reinjury, which suggests that a (so far undefined) period of vulnerability to reinjury may exist during the remodeling phases. The role of individual muscle matrix components and their spatial interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury. Copyright © 2017 the American Physiological Society.

Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion

DEFF Research Database (Denmark)

Carey, A.; Wolsk, Emil; Bruce, C.

2006-01-01

Aims/hypothesis  We compared metabolic gene expression in adipose tissue and skeletal muscle from patients with type 2 diabetes and from well-matched healthy control subjects. We hypothesised that gene expression would be discordantly regulated when comparing the two groups. Our secondary aim...... was to determine the effect of Interleukin-6 (IL6) infusion on circulating adipokines and on gene expression in human adipose tissue. To do this we used real-time RT-PCR. Methods  Both diabetic and control subjects underwent basal skeletal muscle and subcutaneous adipose tissue biopsies. A subset...... necrosis factor alpha, adiponectin and resistin were all unaffected by IL6 infusion, but plasma resistin was lower in the diabetic subjects than in control subjects. Conclusions/interpretation  The observation that PPARGC1A and the PPARs were upregulated in the adipose tissue of type 2 diabetic patients...

Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application

Science.gov (United States)

Dancik, Yuri; Anissimov, Yuri G; Jepps, Owen G; Roberts, Michael S

2012-01-01

AIMS To relate the varying dermal, subcutaneous and muscle microdialysate concentrations found in man after topical application to the nature of the drug applied and to the underlying physiology. METHODS We developed a physiologically based pharmacokinetic model in which transport to deeper tissues was determined by tissue diffusion, blood, lymphatic and intersitial flow transport and drug properties. The model was applied to interpret published human microdialysis data, estimated in vitro dermal diffusion and protein binding affinity of drugs that have been previously applied topically in vivo and measured in deep cutaneous tissues over time. RESULTS Deeper tissue microdialysis concentrations for various drugs in vivo vary widely. Here, we show that carriage by the blood to the deeper tissues below topical application sites facilitates the transport of highly plasma protein bound drugs that penetrate the skin, leading to rapid and significant concentrations in those tissues. Hence, the fractional concentration for the highly plasma protein bound diclofenac in deeper tissues is 0.79 times that in a probe 4.5 mm below a superficial probe whereas the corresponding fractional concentration for the poorly protein bound nicotine is 0.02. Their corresponding estimated in vivo lag times for appearance of the drugs in the deeper probes were 1.1 min for diclofenac and 30 min for nicotine. CONCLUSIONS Poorly plasma protein bound drugs are mainly transported to deeper tissues after topical application by tissue diffusion whereas the transport of highly plasma protein bound drugs is additionally facilitated by convective blood, lymphatic and interstitial transport to deep tissues. PMID:21999217

Hematology, plasma biochemistry, and tissue enzyme activities of invasive red lionfish captured off North Carolina, USA.

Science.gov (United States)

Anderson, E T; Stoskopf, M K; Morris, J A; Clarke, E O; Harms, C A

2010-12-01

The red lionfish Pterois volitans is important not only in the aquarium trade but also as an invasive species in the western Atlantic. Introduced to waters off the southeastern coast of the United States, red lionfish have rapidly spread along much of the East Coast and throughout Bermuda, the Bahamas, and much of the Caribbean. Hematology and plasma biochemistry were evaluated in red lionfish captured from the offshore waters of North Carolina to establish baseline parameters for individual and population health assessment. Blood smears were evaluated for total and differential white blood cell counts, and routine clinical biochemical profiles were performed on plasma samples. To improve the interpretive value of routine plasma biochemistry profiles, tissue enzyme activities (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], lactate dehydrogenase [LD], and creatine kinase [CK]) were analyzed from liver, kidney, skeletal muscle, gastrointestinal tract, and heart tissues from five fish. The hematological and plasma biochemical values were similar to those of other marine teleosts except that the estimated white blood cell counts were much lower than those routinely found in many species. The tissue enzyme activity findings suggest that plasma LD, CK, and AST offer clinical relevance in the assessment of red lionfish.

Initial plasma disappearance and tissue uptake of 131I-albumin in normal rabbits

International Nuclear Information System (INIS)

Bent-Hansen, L.

1991-01-01

The simultaneous plasma disappearance curves of 131I-albumin and 125I-fibrinogen were recorded in normal rabbits for 1 hr. Using fibrinogen as a plasma reference, the disappearance curves of albumin were shown to contain two separate phases of efflux: one fast from zero to 10 min. comprising 8% of the total tracer; and one slow appearing in the interval of 10 to 60 min. containing another 9% of the tracer. Total albumin escape was analyzed to yield an initial slope of 0.024 ± 0.004 min-1, corresponding to a wholebody unidirectional albumin clearance (Cl(0)) of 0.090 ± 0.009 ml(min*100 g)-1. The distribution of efflux was assessed by biopsy uptakes using the same tracers in spleen, kidney, heart, lung, liver, intestine, skin, muscle, and brain. The disappearance curve generally reflects a biphasic pattern of uptake in peripheral tissue, predominantly by muscle and lung. The rapid phase has contributions from the fast near equilibration of liver, and intestine and skin are significant codeterminants of the slow phase. Due to their low body masses highly perfused organs such as kidney, spleen, and heart have little influence on the plasma disappearance. In accordance, the Cl(0) determined for the wholebody was higher than initial clearances found in skin (0.053 ml(min*100 g)-1) and muscle (0.054 ml(min*100 g)-1), but much lower than those found in the highly perfused organs. The initial (unidirectional) rates of peripheral albumin transfer demonstrated, ranged from 10 to 30 times higher than estimates of lymphatic return, suggesting that transcapillary albumin exchange is mediated by high-rate bidirectional diffusion. The rapid decrease of net albumin exchange rates suggests a second, highly significant barrier located within the interstitial matrix, which restricts plasma escape and reduces plasma to lymph albumin transport

Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

Science.gov (United States)

Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

1994-01-01

Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

Human skeletal muscles replaced to a high degree by white adipose tissue.

Science.gov (United States)

Ina, Keisuke; Kitamura, Hirokazu; Masaki, Takayuki; Tatsukawa, Shuji; Yoshimatsu, Hironobu; Fujikura, Yoshihisa

2011-02-01

Extreme replacement of skeletal muscles by adipose tissue was found in an 86-year old Japanese male cadaver during dissection practice for medical students at Oita University School of Medicine. Especially, the bilateral sartorius muscles looked overall like adipose tissue. The man had suffered from diabetes mellitus, renal failure, hypertension and hypothyroidism before his death. He was also an alcohol drinker. He had been bedridden late in life. The cause of death was renal failure. In microscopy, the adipose tissue-like sartorius muscle was shown to consist of leptin-positive adipocytes with a small number of degenerated muscle fibers. Fatty replacement, or fatty degeneration, appears to result from endocrine and metabolic disorders, and being bedridden leads to muscle atrophy and damage, although the origin of the adipocytes which emerged in the degenerated muscles is unknown.

Dynamic adaptation of tendon and muscle connective tissue to mechanical loading

DEFF Research Database (Denmark)

Mackey, Abigail; Heinemeier, Katja Maria; Koskinen, Satu Osmi Anneli

2008-01-01

The connective tissue of tendon and skeletal muscle is a crucial structure for force transmission. A dynamic adaptive capacity of these tissues in healthy individuals is evident from reports of altered gene expression and protein levels of the fibrillar and network-forming collagens, when subjected...... in this article provide strong evidence for the highly adaptable nature of connective tissue in muscle and tendon....

A PEGylated platelet free plasma hydrogel based composite scaffold enables stable vascularization and targeted cell delivery for volumetric muscle loss.

Science.gov (United States)

Aurora, Amit; Wrice, Nicole; Walters, Thomas J; Christy, Robert J; Natesan, Shanmugasundaram

2018-01-01

Extracellular matrix (ECM) scaffolds are being used for the clinical repair of soft tissue injuries. Although improved functional outcomes have been reported, ECM scaffolds show limited tissue specific remodeling response with concomitant deposition of fibrotic tissue. One plausible explanation is the regression of blood vessels which may be limiting the diffusion of oxygen and nutrients across the scaffold. Herein we develop a composite scaffold as a vasculo-inductive platform by integrating PEGylated platelet free plasma (PFP) hydrogel with a muscle derived ECM scaffold (m-ECM). In vitro, adipose derived stem cells (ASCs) seeded onto the composite scaffold differentiated into two distinct morphologies, a tubular network in the hydrogel, and elongated structures along the m-ECM scaffold. The composite scaffold showed a high expression of ITGA5, ITGB1, and FN and a synergistic up-regulation of ang1 and tie-2 transcripts. The in vitro ability of the composite scaffold to provide extracellular milieu for cell adhesion and molecular cues to support vessel formation was investigated in a rodent volumetric muscle loss (VML) model. The composite scaffold delivered with ASCs supported robust and stable vascularization. Additionally, the composite scaffold supported increased localization of ASCs in the defect demonstrating its ability for localized cell delivery. Interestingly, ASCs were observed homing in the injured muscle and around the perivascular space possibly to stabilize the host vasculature. In conclusion, the composite scaffold delivered with ASCs presents a promising approach for scaffold vascularization. The versatile nature of the composite scaffold also makes it easily adaptable for the repair of soft tissue injuries. Decellularized extracellular matrix (ECM) scaffolds when used for soft tissue repair is often accompanied by deposition of fibrotic tissue possibly due to limited scaffold vascularization, which limits the diffusion of oxygen and nutrients

Administration of exercise-conditioned plasma alters muscle catalase kinetics in rat: An argument for in vivo-like Km instead of in vitro-like Vmax

Directory of Open Access Journals (Sweden)

Aristidis S. Veskoukis

2018-05-01

Full Text Available Maximal velocity (Vmax is a well established biomarker for the assessment of tissue redox status. There is scarce evidence, though, that it does not probably reflect sufficiently in vivo tissue redox profile. Instead, the Michaelis constant (Km could more adequately image tissue oxidative stress and, thus, be a more physiologically relevant redox biomarker. Therefore, the aim of the present study was to side-by-side compare Vmax and Km of an antioxidant enzyme after implementing an in vivo set up that induces alterations in tissue redox status. Forty rats were divided into two groups including rats injected with blood plasma originating from rats that had previously swam until exhaustion and rats injected with blood plasma originating from sedentary rats. Tail-vein injections were performed daily for 21 days. Catalase Vmax and Km measured in gastrocnemius muscle were increased after administration of the exercise-conditioned plasma, denoting enhancement of the enzyme activity but impairment of its affinity for the substrate, respectively. These alterations are potential adaptations stimulated by the administered plasma pointing out that blood is an active fluid capable of regulating tissue homeostasis. Our findings suggest that Km adequately reflects in vivo modifications of skeletal muscle catalase and seems to surpass Vmax regarding its physiological relevance and biological interpretation. In conclusion, Km can be regarded as an in vivo-like biomarker that satisfactorily images the intracellular environment, as compared to Vmax that could be aptly parallelized with a biomarker that describes tissue oxidative stress in an in vitro manner.

Enhancement of contractile force generation of artificial skeletal muscle tissues by mild and transient heat treatment.

Science.gov (United States)

Sato, Masanori; Ikeda, Kazushi; Kanno, Shota; Ito, Akira; Kawabe, Yoshinori; Kamihira, Masamichi

2014-01-01

Artificial skeletal muscle tissues composed of cells are expected to be used for applications of regenerative medicine and drug screening. Generally, however, the physical forces generated by tissue-engineered skeletal muscle are lower than those of skeletal muscle tissues found in the body. Local hyperthermia is used for many diseases including muscle injuries. It was recently reported that mild heat treatment improved skeletal muscle functions. In this study, we investigated the effects of mild heat treatment on the tissue-engineered skeletal muscle tissues in vitro. We used magnetite cationic liposomes to label C2C12 myoblast cells magnetically, and constructed densely packed artificial skeletal muscle tissues by using magnetic force. Cell culture at 39°C promoted the differentiation of myoblast cells into myotubes. Moreover, the mild and transient heat treatment improved the contractile properties of artificial skeletal muscle tissue constructs. These findings indicate that the culture method using heat treatment is a useful approach to enhance functions of artificial skeletal muscle tissue.

Tissue Engineered Strategies for Skeletal Muscle Injury

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Umile Giuseppe Longo

2012-01-01

Full Text Available Skeletal muscle injuries are common in athletes, occurring with direct and indirect mechanisms and marked residual effects, such as severe long-term pain and physical disability. Current therapy consists of conservative management including RICE protocol (rest, ice, compression, and elevation, nonsteroidal anti-inflammatory drugs, and intramuscular corticosteroids. However, current management of muscle injuries often does not provide optimal restoration to preinjury status. New biological therapies, such as injection of platelet-rich plasma and stem-cell-based therapy, are appealing. Although some studies support PRP application in muscle-injury management, reasons for concern persist, and further research is required for a standardized and safe use of PRP in clinical practice. The role of stem cells needs to be confirmed, as studies are still limited and inconsistent. Further research is needed to identify mechanisms involved in muscle regeneration and in survival, proliferation, and differentiation of stem cells.

MR muscle tractography study on VX2 soft-tissue tumor in rabbits

International Nuclear Information System (INIS)

Li Yonggang; Guo Liang; Xie Daohai; Hu Chunhogn; Guo Maofeng; Zhu Wei; Chen Jianhua; Xing Jianming; Wang Renfa

2008-01-01

Objective: To determine if diffusion tensor imaging (DTI) and muscle fiber tracts of muscle disease are feasible. Methods: Twenty Newzealand white rabbits were implanted with 0.2 ml VX 2 tumor tissue suspension in the right proximal thighs. MRI and DTI were performed on these rabbits and DTI of muscle fiber tracts in the muscles around the lesions were reconstructed. The fractional anisotropy(FA) and volume ratio anisotropy(VrA) of the tumor and the normal muscle were analyzed. The correlation study between MRI and pathological findings was done. Results: All experimental animal models of rabbit VX 2 soft tissue tumors were successfully established. The difference of FA between the central parenchyma area and the necrosis area, the peripheral area of the tumor, the adjacent and contralateral normal muscle was statistically significant (P 0.05). The difference of FA and VrA between the adjacent and contralateral normal muscle was not statistically significant (P>0.05). The arrangement of normal muscle was regular on DTI of muscle tract. The muscle around the tumor lesions was infiltrated and destructed, which demonstrated irregular and interrupted muscle fiber on muscle tractography. Conclusion: DTI is advantageous to demonstrate the structure of soft tissue tumors and its border, which should be helpful in the structure and function research of muscle, as well as in the diagnosis of muscle diseases. (authors)

Thyroid hormones and deiodinase activity in plasma and tissues in relation to high levels of organohalogen contaminants in East Greenland polar bears (Ursus maritimus).

Science.gov (United States)

Gabrielsen, Kristin Møller; Krokstad, Julie Stene; Villanger, Gro Dehli; Blair, David A D; Obregon, Maria-Jesus; Sonne, Christian; Dietz, Rune; Letcher, Robert J; Jenssen, Bjørn Munro

2015-01-01

Previous studies have shown relationships between organohalogen contaminants (OHCs) and circulating levels of thyroid hormones (THs) in arctic wildlife. However, there is a lack of knowledge concerning the possible functional effects of OHCs on TH status in target tissues for TH-dependent activity. The relationships between circulating (plasma) levels of OHCs and various TH variables in plasma as well as in liver, muscle and kidney tissues from East Greenland sub-adult polar bears (Ursus maritimus) sampled in 2011 (n=7) were therefore investigated. The TH variables included 3.3',5.5'-tetraiodothyronine or thyroxine (T4), 3.3',5-triiodothyronine (T3) and type 1 (D1) and type 2 (D2) deiodinase activities. Principal component analysis (PCA) combined with correlation analyses demonstrated negative relationships between individual polychlorinated biphenyls (PCBs) and their hydroxylated (OH-) metabolites and T4 in both plasma and muscle. There were both positive and negative relationships between individual OHCs and D1 and D2 activities in muscle, liver and kidney tissues. In general, PCBs, OH-PCBs and polybrominated dipehenyl ethers (PBDEs) were positively correlated to D1 and D2 activities, whereas organochlorine pesticides and byproducts (OCPs) were negatively associated with D1 and D2 activities. These results support the hypothesis that OHCs can affect TH status and action in the target tissues of polar bears. TH levels and deiodinase activities in target tissues can be sensitive endpoints for exposure of TH-disrupting compounds in arctic wildlife, and thus, tissue-specific responses in target organs should be further considered when assessing TH disruption in wildlife studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Differences in muscle pain and plasma creatine kinase activity after ...

African Journals Online (AJOL)

encephalopathy,18 and the decrement in muscle power associated with muscle damage.6 ... A high degree of intra-individual variability in plasma. CK activity was ..... 21. Komi PV. Stretch-shortening cycle exercise: a powerful model to study.

A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle.

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Reijo Laaksonen

Full Text Available BACKGROUND: Aggressive lipid lowering with high doses of statins increases the risk of statin-induced myopathy. However, the cellular mechanisms leading to muscle damage are not known and sensitive biomarkers are needed to identify patients at risk of developing statin-induced serious side effects. METHODOLOGY: We performed bioinformatics analysis of whole genome expression profiling of muscle specimens and UPLC/MS based lipidomics analyses of plasma samples obtained in an earlier randomized trial from patients either on high dose simvastatin (80 mg, atorvastatin (40 mg, or placebo. PRINCIPAL FINDINGS: High dose simvastatin treatment resulted in 111 differentially expressed genes (1.5-fold change and p-value<0.05, while expression of only one and five genes was altered in the placebo and atorvastatin groups, respectively. The Gene Set Enrichment Analysis identified several affected pathways (23 gene lists with False Discovery Rate q-value<0.1 in muscle following high dose simvastatin, including eicosanoid synthesis and Phospholipase C pathways. Using lipidomic analysis we identified previously uncharacterized drug-specific changes in the plasma lipid profile despite similar statin-induced changes in plasma LDL-cholesterol. We also found that the plasma lipidomic changes following simvastatin treatment correlate with the muscle expression of the arachidonate 5-lipoxygenase-activating protein. CONCLUSIONS: High dose simvastatin affects multiple metabolic and signaling pathways in skeletal muscle, including the pro-inflammatory pathways. Thus, our results demonstrate that clinically used high statin dosages may lead to unexpected metabolic effects in non-hepatic tissues. The lipidomic profiles may serve as highly sensitive biomarkers of statin-induced metabolic alterations in muscle and may thus allow us to identify patients who should be treated with a lower dose to prevent a possible toxicity.

Assessment of DNA quality in processed tuna muscle tissues

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Zora Piskatá

2016-06-01

Full Text Available Authentication of tuna fish products is necessary to assure consumers of accurate labelling of food products. The quality of species specific DNA crucially affects the efficiency of amplification during the subsequent PCR. The problem in DNA detection in canned products lies in the possibility of the fragmentation of DNA during the processing technologies and the use of ingredients (oil, salt, spice, that may inhibit the PCR reaction. In this study three DNA extraction methods were compared: DNeasy Blood and Tissue Kit, DNeasy mericon Food Kit and Chemagic DNA tissue 10 Kit. The quantity and quality of DNA were evaluated by measuring DNA concentration and ratios A260/A280. Several parameters were estimated: the effect of whole and mechanically treated muscle, sterilization procedure used in canned process (high temperature in combination with high pressure and addition of raw materials. The highest DNA concentrations were observed in non-processed muscle that is not influenced by the sterilization process. Canned whole muscle demonstrated lower DNA yield, and furthermore, the mechanical treatment (canned ground resulted in lower values of DNA concentration that was registered by using all three types of DNA extraction kits. DNeasy mericon Food Kit produced DNA of higher concentration in non-processed sample, Chemagic DNA tissue 10 Kit delivered higher DNA yields than kits DNeasy Blood and Tissue Kit and DNeasy mericon Food Kit in canned samples, although the purity was lower, but still within the range 1.7 - 2.0. DNA was considered to be satisfactorily pure in all three types of samples and using all three types of DNA isolation. In case of the samples enriched of ingredients and treated with sterilization process as whole or ground muscle Chemagic DNA tissue 10 Kit produced in all samples (whole and ground muscle the highest values of DNA concentration, but almost all values of A260/A280 were lower than 1.7. Therefore DNeasy mericon Food Kit

Administration of exercise-conditioned plasma alters muscle catalase kinetics in rat: An argument for in vivo-like Km instead of in vitro-like Vmax.

Science.gov (United States)

Veskoukis, Aristidis S; Paschalis, Vassilis; Kyparos, Antonios; Nikolaidis, Michalis G

2018-05-01

Maximal velocity (V max ) is a well established biomarker for the assessment of tissue redox status. There is scarce evidence, though, that it does not probably reflect sufficiently in vivo tissue redox profile. Instead, the Michaelis constant (K m ) could more adequately image tissue oxidative stress and, thus, be a more physiologically relevant redox biomarker. Therefore, the aim of the present study was to side-by-side compare V max and K m of an antioxidant enzyme after implementing an in vivo set up that induces alterations in tissue redox status. Forty rats were divided into two groups including rats injected with blood plasma originating from rats that had previously swam until exhaustion and rats injected with blood plasma originating from sedentary rats. Tail-vein injections were performed daily for 21 days. Catalase V max and K m measured in gastrocnemius muscle were increased after administration of the exercise-conditioned plasma, denoting enhancement of the enzyme activity but impairment of its affinity for the substrate, respectively. These alterations are potential adaptations stimulated by the administered plasma pointing out that blood is an active fluid capable of regulating tissue homeostasis. Our findings suggest that K m adequately reflects in vivo modifications of skeletal muscle catalase and seems to surpass V max regarding its physiological relevance and biological interpretation. In conclusion, K m can be regarded as an in vivo-like biomarker that satisfactorily images the intracellular environment, as compared to V max that could be aptly parallelized with a biomarker that describes tissue oxidative stress in an in vitro manner. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Strain-time cell death threshold for skeletal muscle in a tissue-engineered model system for deep tissue injury

NARCIS (Netherlands)

Gefen, A.; Nierop, van B.J.; Bader, D.L.; Oomens, C.W.J.

2008-01-01

Deep tissue injury (DTI) is a severe pressure ulcer that results from sustained deformation of muscle tissue overlying bony prominences. In order to understand the etiology of DTI, it is essential to determine the tolerance of muscle cells to large mechanical strains. In this study, a new

Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism

Science.gov (United States)

Thrush, A B; Antoun, G; Nikpay, M; Patten, D A; DeVlugt, C; Mauger, J-F; Beauchamp, B L; Lau, P; Reshke, R; Doucet, É; Imbeault, P; Boushel, R; Gibbings, D; Hager, J; Valsesia, A; Slack, R S; Al-Dirbashi, O Y; Dent, R; McPherson, R; Harper, M-E

2018-01-01

Background/Objectives: Inter-individual variability in weight loss during obesity treatment is complex and poorly understood. Here we use whole body and tissue approaches to investigate fuel oxidation characteristics in skeletal muscle fibers, cells and distinct circulating protein biomarkers before and after a high fat meal (HFM) challenge in those who lost the most (obese diet-sensitive; ODS) vs the least (obese diet-resistant; ODR) amount of weight in a highly controlled weight management program. Subjects/Methods: In 20 weight stable-matched ODS and ODR women who previously completed a standardized clinical weight loss program, we analyzed whole-body energetics and metabolic parameters in vastus lateralis biopsies and plasma samples that were obtained in the fasting state and 6 h after a defined HFM, equivalent to 35% of total daily energy requirements. Results: At baseline (fasting) and post-HFM, muscle fatty acid oxidation and maximal oxidative phosphorylation were significantly greater in ODS vs ODR, as was reactive oxygen species emission. Plasma proteomics of 1130 proteins pre and 1, 2, 5 and 6 h after the HFM demonstrated distinct group and interaction differences. Group differences identified S-formyl glutathione hydratase, heat shock 70 kDA protein 1A/B (HSP72), and eukaryotic translation initiation factor 5 (eIF5) to be higher in ODS vs ODR. Group-time differences included aryl hydrocarbon interacting protein (AIP), peptidylpropyl isomerase D (PPID) and tyrosine protein-kinase Fgr, which increased in ODR vs ODS over time. HSP72 levels correlated with muscle oxidation and citrate synthase activity. These proteins circulate in exosomes; exosomes isolated from ODS plasma increased resting, leak and maximal respiration rates in C2C12 myotubes by 58%, 21% and 51%, respectively, vs those isolated from ODR plasma. Conclusions: Findings demonstrate distinct muscle metabolism and plasma proteomics in fasting and post-HFM states corresponding in diet

Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges.

Science.gov (United States)

Duffy, Rebecca M; Feinberg, Adam W

2014-01-01

Skeletal muscle is a scalable actuator system used throughout nature from the millimeter to meter length scales and over a wide range of frequencies and force regimes. This adaptability has spurred interest in using engineered skeletal muscle to power soft robotics devices and in biotechnology and medical applications. However, the challenges to doing this are similar to those facing the tissue engineering and regenerative medicine fields; specifically, how do we translate our understanding of myogenesis in vivo to the engineering of muscle constructs in vitro to achieve functional integration with devices. To do this researchers are developing a number of ways to engineer the cellular microenvironment to guide skeletal muscle tissue formation. This includes understanding the role of substrate stiffness and the mechanical environment, engineering the spatial organization of biochemical and physical cues to guide muscle alignment, and developing bioreactors for mechanical and electrical conditioning. Examples of engineered skeletal muscle that can potentially be used in soft robotics include 2D cantilever-based skeletal muscle actuators and 3D skeletal muscle tissues engineered using scaffolds or directed self-organization. Integration into devices has led to basic muscle-powered devices such as grippers and pumps as well as more sophisticated muscle-powered soft robots that walk and swim. Looking forward, current, and future challenges include identifying the best source of muscle precursor cells to expand and differentiate into myotubes, replacing cardiomyocytes with skeletal muscle tissue as the bio-actuator of choice for soft robots, and vascularization and innervation to enable control and nourishment of larger muscle tissue constructs. © 2013 Wiley Periodicals, Inc.

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...

Current opportunities and challenges in skeletal muscle tissue engineering

NARCIS (Netherlands)

Koning, Merel; Harmsen, Martin C; van Luyn, Marja J A; Werker, Paul M N

The purpose of this article is to give a concise review of the current state of the art in tissue engineering (TE) of skeletal muscle and the opportunities and challenges for future clinical applicability. The endogenous progenitor cells of skeletal muscle, i.e. satellite cells, show a high

Quantitative ultrasound tissue characterization in shoulder and thigh muscles – a new approach

Directory of Open Access Journals (Sweden)

Jørgensen Kurt

2006-01-01

Full Text Available Abstract Background The echogenicity patterns of ultrasound scans contain information of tissue composition in muscles. The aim was: (1 to develop a quantitative ultrasound image analysis to characterize tissue composition in terms of intensity and structure of the ultrasound images, and (2 to use the method for characterization of ultrasound images of the supraspinatus muscle, and the vastus lateralis muscle. Methods Computerized texture analyses employing first-order and higher-order grey-scale statistics were developed to objectively characterize ultrasound images of m. supraspinatus and m. vastus lateralis from 9 healthy participants. Results The mean grey-scale intensity was higher in the vastus lateralis muscle (p -2 and for m. supraspinatus: 0.016 mm-2. Conclusion The higher intensity and the higher number of blobs in the vastus lateralis muscle indicates that the thigh muscle contained more non-contractile components than the supraspinatus muscle, and that the muscle was coarser. The image analyses supplemented each other and gave a more complete description of the tissue composition in the muscle than the mean grey-scale value alone.

Connective tissue injury in calf muscle tears and return to play: MRI correlation.

Science.gov (United States)

Prakash, Ashutosh; Entwisle, Tom; Schneider, Michal; Brukner, Peter; Connell, David

2017-10-26

The aim of our study was to assess a group of patients with calf muscle tears and evaluate the integrity of the connective tissue boundaries and interfaces. Further, we propose a novel MRI grading system based on integrity of the connective tissue and assess any correlation between the grading score and time to return to play. We have also reviewed the anatomy of the calf muscles. We retrospectively evaluated 100 consecutive patients with clinical suspicion and MRI confirmation of calf muscle injury. We evaluated each calf muscle tear with MRI for the particular muscle injured, location of injury within the muscle and integrity of the connective tissue structure at the interface. The muscle tears were graded 0-3 depending on the degree of muscle and connective tissue injury. The time to return to play for each patient and each injury was found from the injury records and respective sports doctors. In 100 patients, 114 injuries were detected. Connective tissue involvement was observed in 63 out of 100 patients and failure (grade 3 injury) in 18. Mean time to return to play with grade 0 injuries was 8 days, grade 1 tears was 17 days, grade 2 tears was 25 days and grade 3 tears was 48 days (pmuscle tears. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Skeletal muscle aging: stem cell function and tissue homeostasis

OpenAIRE

Victor, Pedro Sousa

2012-01-01

Muscle aging, in particular, is characterized by the reduction of tissue mass and function, which are particularly prominent in geriatric individuals undergoing sarcopenia. The age-associated muscle wasting is also associated with a decline in regenerative ability and a reduction in resident muscle stem cell (satellite cell) number and function. Although sarcopenia is one of the major contributors to the general loss of physiological function, the mechanisms involved in age-related loss of mu...

Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury

DEFF Research Database (Denmark)

Mackey, Abigail Louise; Kjaer, Michael

2017-01-01

Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibres as they undergo necrosis, followed closely by satellite cell mediated myogenesis, have been mapped in detail. Much less is known about...... the adaptation throughout this process of both the connective tissue structures surrounding the myofibres, and the fibroblasts, the cells responsible for synthesising this connective tissue. However, the few studies investigating muscle connective tissue remodelling demonstrate a strong response that appears...

β-adrenergic relaxation of smooth muscle: differences between cells and tissues

International Nuclear Information System (INIS)

Scheid, C.R.

1987-01-01

The present studies were carried out in an attempt to resolve the controversy about the Na + dependence of β-adrenergic relaxation in smooth muscle. Previous studies on isolated smooth muscle cells from the toad stomach had suggested that at least some of the actions of β-adrenergic agents, including a stimulatory effect on 45 Ca efflux, were dependent on the presence of a normal transmembrane Na + gradient. Studies by other investigators using tissues derived from mammalian sources had suggested that the relaxing effect of β-adrenergic agents was Na + independent. Uncertainty remained as to whether these discrepancies reflected differences between cells and tissues or differences between species. Thus, in the present studies, the authors utilized both tissues and cells from the same source, the stomach muscle of the toad Bufo marinus, and assessed the Na + dependence of β-adrenergic relaxation. They found that elimination of a normal Na + gradient abolished β-adrenergic relaxation of isolated cells. In tissues, however, similar manipulations had no effect on relaxation. The reasons for this discrepancy are unclear but do not appear to be attributable to changes in smooth muscle function following enzymatic dispersion. Thus the controversy concerning the mechanisms of β-adrenergic relaxation may reflect inherent differences between tissues and cells

Tenascin-Y, a component of distinctive connective tissues, supports muscle cell growth.

Science.gov (United States)

Hagios, C; Brown-Luedi, M; Chiquet-Ehrismann, R

1999-12-15

Chicken tenascin-Y is an extracellular matrix protein most closely related to the mammalian tenascin-X. It is highly expressed in the connective tissue of skeletal muscle (C. Hagios, M. Koch, J. Spring, M. Chiquet, and R. Chiquet-Ehrismann, 1996, J. Cell Biol. 134, 1499-1512). Here we demonstrate the presence of tenascin-Y in specific areas of the connective tissues in developing lung, kidney, and skin. In skin tenascin-Y shows a complementary expression pattern to tenascin-C, whereas in the lung and kidney the sites of expression are partly overlapping. Tenascin-Y is also present in embryonic skeletal muscle where it is expressed in the developing connective tissue in between the muscle fibers. This connective tissue is also the major site of alpha5 integrin expression. We purified recombinantly expressed tenascin-Y and tested its effect on cell adhesion and its influence on muscle cell growth and differentiation. C2C12 myoblasts were able to adhere to tenascin-Y and showed extensive formation of actin-rich processes without generation of stress fibers. Furthermore, we found that tenascin-Y influenced cell morphology of chick embryo fibroblasts over prolonged times in culture and that it supports primary muscle cell growth and restricts muscle cell differentiation. Copyright 1999 Academic Press.

Glucose rapidly decreases plasma membrane GLUT4 content in rat skeletal muscle.

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Marette, A; Dimitrakoudis, D; Shi, Q; Rodgers, C D; Klip, A; Vranic, M

1999-02-01

We have previously demonstrated that chronic hyperglycemia per se decreases GLUT4 glucose transporter expression and plasma membrane content in mildly streptozotocin- (STZ) diabetic rats (Biochem. J. 284, 341-348, 1992). In the present study, we investigated the effect of an acute rise in glycemia on muscle GLUT4 and GLUT1 protein contents in the plasma membrane, in the absence of insulin elevation. Four experimental groups of rats were analyzed in the postabsorptive state: 1. Control rats. 2. Hyperglycemic STZ-diabetic rats with moderately reduced fasting insulin levels. 3. STZ-diabetic rats made normoglycemic with phlorizin treatment. 4. Phlorizin-treated (normoglycemic) STZ-diabetic rats infused with glucose for 40 min. The uniqueness of the latter model is that glycemia can be rapidly raised without any concomitant increase in plasma insulin levels. Plasma membranes were isolated from hindlimb muscle and GLUT1 and GLUT4 proteins amounts determined by Western blot analysis. As predicted, STZ-diabetes caused a significant decrease in the abundance of GLUT4 in the isolated plasma membranes. Normalization of glycemia for 3 d with phlorizin treatment restored plasma membrane GLUT4 content in muscle of STZ-diabetic rats. A sudden rise in glycemia over a period of 40 min caused the GLUT4 levels in the plasma membrane fraction to decrease to those of nontreated STZ-diabetic rats. In contrast to the GLUT4 transporter, plasma membrane GLUT1 abundance was not changed by the acute glucose challenge. It is concluded that glucose can have regulatory effect by acutely reducing plasma membrane GLUT4 protein contents in rat skeletal muscle. We hypothesize that this glucose-induced downregulation of plasma membrane GLUT4 could represent a protective mechanism against excessive glucose uptake under hyperglycemic conditions accompanied by insulin resistance.

Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.

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Grant, R W; Vester Boler, B M; Ridge, T K; Graves, T K; Swanson, K S

2013-08-01

Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation

Methylation-sensitive amplification polymorphism analysis of fat and muscle tissues in pigs.

Science.gov (United States)

Ma, J D; Li, M Z; Zhou, S L; Zhou, C W; Li, X W

2012-09-26

DNA methylation may be involved in regulating the expression of protein-coding genes, resulting in different fat and muscle phenotypes. Using a methylation-sensitive amplified polymorphism approach, we obtained 7423 bands by selective amplification of genomic DNA from six different fat depots and two heterogeneous muscle types from Duroc/Landrace/Yorkshire cross-bred pigs. The degrees of DNA methylation, determined by the percentages of hemi- and fully methylated sites relative to the total number of CCGG sites, were similar in male and female pigs for each specific tissue [χ(2) test; P (two-tailed) > 0.05]. Gender bias was therefore ignored. There were significant differences in the degree of DNA methylation among the eight tissue types [χ(2) test; P(total) (two-tailed) = 0.009]. However, similar degrees of methylation were observed among the six fat depots [χ(2) test; P(fat) (two-tailed) = 0.24 > 0.05]and between the two muscle types [χ(2) test; P(muscle) (two-tailed) = 0.76 > 0.05]. We conclude that the degree of DNA methylation differs between porcine fat and muscle tissue, but that the methylation status of a particular tissue type is similar, despite being deposited at different body sites.

Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends.

Science.gov (United States)

Qazi, Taimoor H; Mooney, David J; Pumberger, Matthias; Geissler, Sven; Duda, Georg N

2015-01-01

Skeletal muscles have a robust capacity to regenerate, but under compromised conditions, such as severe trauma, the loss of muscle functionality is inevitable. Research carried out in the field of skeletal muscle tissue engineering has elucidated multiple intrinsic mechanisms of skeletal muscle repair, and has thus sought to identify various types of cells and bioactive factors which play an important role during regeneration. In order to maximize the potential therapeutic effects of cells and growth factors, several biomaterial based strategies have been developed and successfully implemented in animal muscle injury models. A suitable biomaterial can be utilized as a template to guide tissue reorganization, as a matrix that provides optimum micro-environmental conditions to cells, as a delivery vehicle to carry bioactive factors which can be released in a controlled manner, and as local niches to orchestrate in situ tissue regeneration. A myriad of biomaterials, varying in geometrical structure, physical form, chemical properties, and biofunctionality have been investigated for skeletal muscle tissue engineering applications. In the current review, we present a detailed summary of studies where the use of biomaterials favorably influenced muscle repair. Biomaterials in the form of porous three-dimensional scaffolds, hydrogels, fibrous meshes, and patterned substrates with defined topographies, have each displayed unique benefits, and are discussed herein. Additionally, several biomaterial based approaches aimed specifically at stimulating vascularization, innervation, and inducing contractility in regenerating muscle tissues are also discussed. Finally, we outline promising future trends in the field of muscle regeneration involving a deeper understanding of the endogenous healing cascades and utilization of this knowledge for the development of multifunctional, hybrid, biomaterials which support and enable muscle regeneration under compromised conditions

The Effects of Muscle Mass on Homocyst(e)ine Levels in Plasma and Urine.

Science.gov (United States)

Malinow, M René; Lister, Craig L; DE Crée, Carl

The present study was designed to examine the relationship between homocyst(e)ine (H[e]) levels and muscle mass. Two experimental groups each of 24 Caucasian males, one consisting of higher-muscle mass subjects (HMM) and the other of lower-muscle mass subjects (LMM) participated in this study. Muscle mass was estimated from 24-hour urine collections of creatinine (Crt). Muscle mass was 40.3 ± 15.9 kg in HMM and 37.2 ± 11.4 kg in LMM (P= 0.002). Mean plasma H(e) levels in HMM were 10.29 ± 2.9 nmol/mL, and in LMM were 10.02 ± 2.4 nmol/L (Not significant, [NS]). Urinary H(e) levels (UH[e]) were 9.95 ± 4.3 nmol/mL and 9.22 ± 2.9 nmol/mL for HMM and LMM, respectively (NS). Plasma H(e) levels correlated well with UH(e) (HMM: r= 0.58, P= 0.009; LMM: r= 0.66, P= 0.004). Muscle mass and was not correlated to either plasma H(e) or UH(e). However, in HMM trends were identified for body mass to be correlated with UH(e) (r= 0.39, P= 0.10) and UCrt (r= 0.41, P= 0.08). Surprisingly, in HMM plasma and UCrt were only weakly correlated (r= 0.44, P= 0.06). Our results do not support a causal relationship between the amount of muscle mass and H(e) levels in plasma or urine.

Low-intensity infrared lasers alter actin gene expression in skin and muscle tissue

International Nuclear Information System (INIS)

Fonseca, A S; Mencalha, A L; Campos, V M A; Ferreira-Machado, S C; Peregrino, A A F; Magalhães, L A G; Geller, M; Paoli, F

2013-01-01

The biostimulative effect of low-intensity lasers is the basis for treatment of diseases in soft tissues. However, data about the influence of biostimulative lasers on gene expression are still scarce. The aim of this work was to evaluate the effects of low-intensity infrared lasers on the expression of actin mRNA in skin and muscle tissue. Skin and muscle tissue of Wistar rats was exposed to low-intensity infrared laser radiation at different fluences and frequencies. One and 24 hours after laser exposure, tissue samples were withdrawn for total RNA extraction, cDNA synthesis and evaluation of actin gene expression by quantitative polymerase chain reaction. The data obtained show that laser radiation alters the expression of actin mRNA differently in skin and muscle tissue of Wistar rats depending of the fluence, frequency and time after exposure. The results could be useful for laser dosimetry, as well as to justify the therapeutic protocols for treatment of diseases of skin and muscle tissues based on low-intensity infrared laser radiation. (paper)

A swimming robot actuated by living muscle tissue

Directory of Open Access Journals (Sweden)

Herr Hugh

2004-10-01

Full Text Available Abstract Biomechatronics is the integration of biological components with artificial devices, in which the biological component confers a significant functional capability to the system, and the artificial component provides specific cellular and tissue interfaces that promote the maintenance and functional adaptation of the biological component. Based upon functional performance, muscle is potentially an excellent mechanical actuator, but the larger challenge of developing muscle-actuated, biomechatronic devices poses many scientific and engineering challenges. As a demonstratory proof of concept, we designed, built, and characterized a swimming robot actuated by two explanted frog semitendinosus muscles and controlled by an embedded microcontroller. Using open loop stimulation protocols, the robot performed basic swimming maneuvers such as starting, stopping, turning (turning radius ~400 mm and straight-line swimming (max speed >1/3 body lengths/second. A broad spectrum antibiotic/antimycotic ringer solution surrounded the muscle actuators for long term maintenance, ex vivo. The robot swam for a total of 4 hours over a 42 hour lifespan (10% duty cycle before its velocity degraded below 75% of its maximum. The development of functional biomechatronic prototypes with integrated musculoskeletal tissues is the first critical step toward the long term objective of controllable, adaptive and robust biomechatronic robots and prostheses.

Monitoring temporal microstructural variations of skeletal muscle tissues by multispectral Mueller matrix polarimetry

Science.gov (United States)

Dong, Yang; He, Honghui; He, Chao; Ma, Hui

2017-02-01

Mueller matrix polarimetry is a powerful tool for detecting microscopic structures, therefore can be used to monitor physiological changes of tissue samples. Meanwhile, spectral features of scattered light can also provide abundant microstructural information of tissues. In this paper, we take the 2D multispectral backscattering Mueller matrix images of bovine skeletal muscle tissues, and analyze their temporal variation behavior using multispectral Mueller matrix parameters. The 2D images of the Mueller matrix elements are reduced to the multispectral frequency distribution histograms (mFDHs) to reveal the dominant structural features of the muscle samples more clearly. For quantitative analysis, the multispectral Mueller matrix transformation (MMT) parameters are calculated to characterize the microstructural variations during the rigor mortis and proteolysis processes of the skeletal muscle tissue samples. The experimental results indicate that the multispectral MMT parameters can be used to judge different physiological stages for bovine skeletal muscle tissues in 24 hours, and combining with the multispectral technique, the Mueller matrix polarimetry and FDH analysis can monitor the microstructural variation features of skeletal muscle samples. The techniques may be used for quick assessment and quantitative monitoring of meat qualities in food industry.

An acellular biologic scaffold does not regenerate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury.

Science.gov (United States)

Aurora, Amit; Roe, Janet L; Corona, Benjamin T; Walters, Thomas J

2015-10-01

Extracellular matrix (ECM) derived scaffolds continue to be investigated for the treatment of volumetric muscle loss (VML) injuries. Clinically, ECM scaffolds have been used for lower extremity VML repair; in particular, MatriStem™, a porcine urinary bladder matrix (UBM), has shown improved functional outcomes and vascularization, but limited myogenesis. However, efficacy of the scaffold for the repair of traumatic muscle injuries has not been examined systematically. In this study, we demonstrate that the porcine UBM scaffold when used to repair a rodent gastrocnemius musculotendinous junction (MTJ) and tibialis anterior (TA) VML injury does not support muscle tissue regeneration. In the MTJ model, the scaffold was completely resorbed without tissue remodeling, suggesting that the scaffold may not be suitable for the clinical repair of muscle-tendon injuries. In the TA VML injury, the scaffold remodeled into a fibrotic tissue and showed functional improvement, but not due to muscle fiber regeneration. The inclusion of physical rehabilitation also did not improve functional response or tissue remodeling. We conclude that the porcine UBM scaffold when used to treat VML injuries may hasten the functional recovery through the mechanism of scaffold mediated functional fibrosis. Thus for appreciable muscle regeneration, repair strategies that incorporate myogenic cells, vasculogenic accelerant and a myoconductive scaffold need to be developed. Published by Elsevier Ltd.

Effects of a combined mechanical stimulation protocol: Value for skeletal muscle tissue engineering

NARCIS (Netherlands)

Boonen, K.J.M.; Langelaan, M.L.P.; Polak, R.B.; Schaft, van der D.W.J.; Baaijens, F.P.T.; Post, M.J.

2010-01-01

Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications for regenerative medicine, in vitro physiological model systems, and in vitro meat production. Besides conventional biochemical cues to promote muscle tissue maturation in vitro, biophysical stimuli

Muscle connective tissue content of endurance-trained and inactive individuals

DEFF Research Database (Denmark)

Mackey, Abigail; Donnelly, A E; Roper, H P

2005-01-01

Although it is known that exercise exerts a positive regulatory effect on collagen synthesis, the effects of endurance training on muscle endomysial connective tissue in man are not so well documented. To investigate this, a single muscle biopsy was collected from two groups of volunteers...

Tolerance to low temperatures of Toxocara cati larvae in chicken muscle tissue

DEFF Research Database (Denmark)

Taira, Kensuke; Saitoh, Yasuhide; Okada, Natsuki

2012-01-01

Infectivity of Toxocara cati larvae in muscle tissue of chickens after storage at 4 degrees C and -25 degrees C was assessed in a mouse bioassay to provide information on the risk of meat-borne toxocarosis. Muscle tissue samples of 30-day old T. cati infections were stored at 4 degrees C for 14...

Biochemical composition of muscle tissue of penaeid prawns

Digital Repository Service at National Institute of Oceanography (India)

Achuthankutty, C.T.; Parulekar, A.H.

Biochemical composition of muscle tissue of females belonging to four species of penaeid prawns, viz. Metapenaeus affinis, M. dobsoni, Penaeus merguiensis and Parapenaeopsis stylifera, inhabiting the coastal waters of Goa, India, was estimated...

Ontogenesis of muscle and adipose tissues and their interactions in ruminants and other species.

Science.gov (United States)

Bonnet, M; Cassar-Malek, I; Chilliard, Y; Picard, B

2010-07-01

The lean-to-fat ratio, that is, the relative masses of muscle and adipose tissue, is a criterion for the yield and quality of bovine carcasses and meat. This review describes the interactions between muscle and adipose tissue (AT) that may regulate the dynamic balance between the number and size of muscle v. adipose cells. Muscle and adipose tissue in cattle grow by an increase in the number of cells (hyperplasia), mainly during foetal life. The total number of muscle fibres is set by the end of the second trimester of gestation. By contrast, the number of adipocytes is never set. Number of adipocytes increases mainly before birth until 1 year of age, depending on the anatomical location of the adipose tissue. Hyperplasia concerns brown pre-adipocytes during foetal life and white pre-adipocytes from a few weeks after birth. A decrease in the number of secondary myofibres and an increase in adiposity in lambs born from mothers severely underfed during early pregnancy suggest a balance in the commitment of a common progenitor into the myogenic or adipogenic lineages, or a reciprocal regulation of the commitment of two distinct progenitors. The developmental origin of white adipocytes is a subject of debate. Molecular and histological data suggested a possible transdifferentiation of brown into white adipocytes, but this hypothesis has now been challenged by the characterization of distinct precursor cells for brown and white adipocytes in mice. Increased nutrient storage in fully differentiated muscle fibres and adipocytes, resulting in cell enlargement (hypertrophy), is thought to be the main mechanism, whereby muscle and fat masses increase in growing cattle. Competition or prioritization between adipose and muscle cells for the uptake and metabolism of nutrients is suggested, besides the successive waves of growth of muscle v. adipose tissue, by the inhibited or delayed adipose tissue growth in bovine genotypes exhibiting strong muscular development. This

Photobiomodulation in human muscle tissue: an advantage in sports performance?

Science.gov (United States)

Ferraresi, Cleber; Huang, Ying-Ying; Hamblin, Michael R

2016-12-01

Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to stimulate, heal, and regenerate damaged tissue. Both preconditioning (light delivered to muscles before exercise) and PBM applied after exercise can increase sports performance in athletes. This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The parameters used were categorized into those with positive effects or no effects on muscle performance and recovery. Randomized controlled trials and case-control studies in both healthy trained and untrained participants, and elite athletes were retrieved from MEDLINE up to 2016. Performance metrics included fatigue, number of repetitions, torque, hypertrophy; measures of muscle damage and recovery such as creatine kinase and delayed onset muscle soreness. Searches retrieved 533 studies, of which 46 were included in the review (n = 1045 participants). Studies used single laser probes, cluster of laser diodes, LED clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be permitted in athletic competition by international regulatory authorities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

Directory of Open Access Journals (Sweden)

Marcelo G. Pereira

2014-09-01

Full Text Available This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA. Young male Wistar rats were supplemented with leucine (1.35 g/kg per day; then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA of regenerating myofibers (p > 0.05 from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I and Smad2/3 in regenerating muscles (p < 0.05. Leucine also reduced neonatal myosin heavy chain (MyHC-n (p < 0.05, increased adult MyHC-II expression (p < 0.05 and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05. Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

Association between selenium plasma levels and muscle function in hemodialysis patients

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Milena B Stockler-Pinto

2012-06-01

Full Text Available Selenium (Se is a well-known antioxidant with a critical role in the proper functioning of nervous and muscle functions. In the last decade, many authors have suggested that Se may be a potent protective agent for neurons and myocytes through selenoprotein expression in the brain, as well as in skeletal and cardiac muscles. Low Se status has been associated with reduced coordination, motor speed and muscle strength. Reduced muscle function is common in hemodialysis (HD patients; however, no study evaluated the association between muscle function and Se levels in HD patients. The objective of this study was to correlate muscle function with Se plasma levels in HD patients. Twenty HD patients (12 men, 54.5±15.2 yr; 81.7±52.8 months on HD from RenalCor Clinic at Rio de Janeiro, Brazil were studied. Blood samples were collected during fasting, before a regular HD session. The Se plasma levels were determined by atomic absorption spectrophotometry with hydride generation (Hitachi, Z-500 and handgrip strength (HGS was measured three times with a mechanical dynamometer (Jamar after HD sessions in the non-fistula side and the highest value was used for analysis. HGS values less than the 10th percentile of an age-, gender- and regional specific reference were considered as muscle function loss. Plasma Se levels (31.9±14.8 μg/L were below the normal range (60-120 μg/L and all patients were Se deficient. HGS values were significantly greater in males (31.0±11.5 kg vs 14.0±6.8 kg for females (p=0.001 and the muscle function loss was observed in 50% of patients and, those with muscle function loss presented low Se levels (26.5±12.1 μg/L when compared to patients with preserved muscle function (39.12±14.5 μg/L (p=0.05. These data suggest that Se can have an important role on muscle function in HD patients. However, more research is needed to better understand this possible relationship in CKD patients.

Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects

DEFF Research Database (Denmark)

Bruun, Jens M; Helge, Jørn W; Richelsen, Bjørn

2006-01-01

Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle...... (SM) in 27 severely obese subjects (mean body mass index: 45.8 kg/m2). Plasma samples, subcutaneous abdominal AT biopsies, and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR. The intervention reduced body weight (P

On the search for new anticancer drugs 14: the plasma pharmacokinetics and tissue distribution of spin-labeled thio-TEPA (SL-O-TT).

Science.gov (United States)

Gutierrez, P L; Cohen, B E; Sosnovsky, G; Davis, T A; Egorin, M J

1985-01-01

We defined the plasma and tissue concentrations and pharmacokinetics of SL-O-TT, a spin-labeled analog of thio-TEPA, in 35-44-g male Swiss Webster mice that had received spin-labeled thio-TEPA at a dosage of 10 mg/kg. Concentrations of spin-labeled thio-TEPA in ethyl acetate extracts of tissue and plasma were determined by gas-liquid chromatography and electron spin resonance spectroscopy. Plasma concentrations of spin-labeled thio-TEPA declined in a biexponential fashion that was well described by the equation: Ct = 21.5e-0.276t + 2.30e-0.026t indicating a half-life alpha of 2.5 min and a half-life beta of 26.6 min. After 2 h there was still spin-labeled thio-TE-PA in plasma, but not in tissues. In tissues, no spin-labeled thio-TEPA was detected with gas-liquid chromatography 15 min after injection, but with electron-spin resonance label was found in lung and skeletal muscle. The main metabolite of spin-labeled thio-TEPA is spin-labeled TEPA, where oxidative desulfurization is invoked as the main metabolic mechanism. Reduction of the spin label to the hydroxylamine was also observed with time.

Development and evaluation of a removable tissue-engineered muscle with artificial tendons.

Science.gov (United States)

Nakamura, Tomohiro; Takagi, Shunya; Kamon, Takafumi; Yamasaki, Ken-Ichi; Fujisato, Toshia

2017-02-01

Tissue-engineered skeletal muscles were potentially useful as physiological and biochemical in vitro models. Currently, most of the similar models were constructed without tendons. In this study, we aimed to develop a simple, highly versatile tissue-engineered muscle with artificial tendons, and to evaluate the contractile, histological and molecular dynamics during differentiation. C2C12 cells were embedded in a cold type-І collagen gel and placed between two artificial tendons on a silicone sheet. The construct shrank and tightly attached to the artificial tendons with differentiation, finally detaching from the silicone sheet within 1 week of culture onset. We successfully developed a tissue-engineered skeletal muscle with two artificial tendons from C2C12 myoblasts embedded in type-І collagen gel. The isometric twitch contractile force (TCF) significantly increased during differentiation. Time to Peak Tension (TPT) and Half-Relaxation Time (1/2RT) were significantly shortened during differentiation. Myogenic regulatory factors were maximally expressed at 2 weeks, and subsequently decreased at 3 weeks of culture. Histological analysis indicated that myotube formation increased markedly from 2 weeks and well-ordered sarcomere structures were observed on the surface of the 3D engineered muscle at 3 weeks of culture. These results suggested that robust muscle structure occurred by 3 weeks in the tissue-engineered skeletal muscle. Moreover, during the developmental process, the artificial tendons might contribute to well-ordered sarcomere formation. Our results indicated that this simple culture system could be used to evaluate the effects of various pharmacological and mechanical cues on muscle contractility in a variety of research areas. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Cyclic AMP system in muscle tissue during prolonged hypokinesia

Science.gov (United States)

Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.

1980-01-01

Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

Histological Evaluation of Decellularized Skeletal Muscle Tissue Using Two Different Decellularization Agents

Directory of Open Access Journals (Sweden)

Hana Hrebíková

2017-02-01

Full Text Available The aim of the present study was to determine effect of two decellularized agents, sodium dodecyl sulphate (SDS and Triton X-100, to the skeletal muscle tissue. Final scaffold was evaluated by several histological techniques to analyse preservation of essential structures including collagen and elastic fibres, basement membranes, glycosaminoglycans and also to confirm elimination of nuclear and cytoplasmic components which are redundant in effectively prepared decellularized scaffolds. Comparison of tissue scaffolds processed with different detergents proved that SDS is superior to Triton X-100 as it can effectively decellularize muscle tissue.

The assessment of cold atmospheric plasma treatment of DNA in synthetic models of tissue fluid, tissue and cells

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Szili, Endre J.; Gaur, Nishtha; Hong, Sung-Ha; Kurita, Hirofumi; Oh, Jun-Seok; Ito, Masafumi; Mizuno, Akira; Hatta, Akimitsu; Cowin, Allison J.; Graves, David B.; Short, Robert D.

2017-07-01

There is a growing literature database that demonstrates the therapeutic potential of cold atmospheric plasma (herein referred to as plasma). Given the breadth of proposed applications (e.g. from teeth whitening to cancer therapy) and vast gamut of plasma devices being researched, it is timely to consider plasma interactions with specific components of the cell in more detail. Plasma can produce highly reactive oxygen and nitrogen species (RONS) such as the hydroxyl radical (OH•), peroxynitrite (ONOO-) and superoxide (\\text{O}2- ) that would readily modify essential biomolecules such as DNA. These modifications could in principle drive a wide range of biological processes. Against this possibility, the reported therapeutic action of plasmas are not underpinned by a particularly deep knowledge of the potential plasma-tissue, -cell or -biomolecule interactions. In this study, we aim to partly address this issue by developing simple models to study plasma interactions with DNA, in the form of DNA-strand breaks. This is carried out using synthetic models of tissue fluid, tissue and cells. We argue that this approach makes experimentation simpler, more cost-effective and faster than compared to working with real biological materials and cells. Herein, a helium plasma jet source was utilised for these experiments. We show that the plasma jet readily induced DNA-strand breaks in the tissue fluid model and in the cell model, surprisingly without any significant poration or rupture of the phospholipid membrane. In the plasma jet treatment of the tissue model, DNA-strand breaks were detected in the tissue mass after pro-longed treatment (on the time-scale of minutes) with no DNA-strand breaks being detected in the tissue fluid model underneath the tissue model. These data are discussed in the context of the therapeutic potential of plasma.

Plasma and muscle myostatin in relation to type 2 diabetes

DEFF Research Database (Denmark)

Brandt, Claus; Nielsen, Anders R; Fischer, Christian P

2012-01-01

Myostatin is a secreted growth factor expressed in skeletal muscle tissue, which negatively regulates skeletal muscle mass. Recent animal studies suggest a role for myostatin in insulin resistance. We evaluated the possible metabolic role of myostatin in patients with type 2 diabetes and healthy...

Platelet-rich plasma (PRP for acute muscle injury: a systematic review.

Directory of Open Access Journals (Sweden)

Mohamad Shariff A Hamid

Full Text Available INTRODUCTION: Acute muscle injury is one of the commonest injuries that often result in loss of training and competition time. The best management for muscle injury has not been identified. Sports medicine practitioners used several approaches in attempt to accelerate time to recovery from muscle injury. More recently growing interest focussed on autologous blood product injection. METHODS: A literature search was conducted systematically using OvidMEDLINE, PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published until December 2012. Controlled trials and controlled laboratory studies comparing different strategies to promote early recovery of muscle injury were included. The methodological quality of studies was assessed. RESULTS: There are limited studies on the effects of PRP therapy for muscle injury. Three in vivo laboratory studies and one pilot human study were reviewed. The laboratory studies reported histological evidence on significant acceleration of muscle healing in animals treated with autologous conditioned serum (ACS, platelet-rich plasma (PRP and platelet rich fibrin matrix (PRFM. A pilot human study found athletes treated with repeated ACS injection recovers significantly faster than retrospective controls. CONCLUSION: Several in vivo laboratory studies suggest beneficial effects of ACS, PRP and PRFM in accelerating muscle recovery. Evidence to suggest similar effects on humans is however limited, as valuable information from robust human controlled trials is still not available at this moment. Hence, more studies of satisfactory methodological quality with platelet-rich plasma interventions on muscle injury are justified.

Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins

International Nuclear Information System (INIS)

Sakai, T.; Kisiel, W.

1990-01-01

Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which 125 I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity

Calprotectin is released from human skeletal muscle tissue during exercise

DEFF Research Database (Denmark)

Mortensen, Ole Hartvig; Andersen, Kasper; Fischer, Christian

2008-01-01

Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained...... in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at approximately 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known...... as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of approximately 50...

Quantitatively differentiating microstructural variations of skeletal muscle tissues by multispectral Mueller matrix imaging

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Dong, Yang; He, Honghui; He, Chao; Ma, Hui

2016-10-01

Polarized light is sensitive to the microstructures of biological tissues and can be used to detect physiological changes. Meanwhile, spectral features of the scattered light can also provide abundant microstructural information of tissues. In this paper, we take the backscattering polarization Mueller matrix images of bovine skeletal muscle tissues during the 24-hour experimental time, and analyze their multispectral behavior using quantitative Mueller matrix parameters. In the processes of rigor mortis and proteolysis of muscle samples, multispectral frequency distribution histograms (FDHs) of the Mueller matrix elements can reveal rich qualitative structural information. In addition, we analyze the temporal variations of the sample using the multispectral Mueller matrix transformation (MMT) parameters. The experimental results indicate that the different stages of rigor mortis and proteolysis for bovine skeletal muscle samples can be judged by these MMT parameters. The results presented in this work show that combining with the multispectral technique, the FDHs and MMT parameters can characterize the microstructural variation features of skeletal muscle tissues. The techniques have the potential to be used as tools for quantitative assessment of meat qualities in food industry.

Maternal nutrition induces gene expression changes in fetal muscle and adipose tissues in sheep.

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Peñagaricano, Francisco; Wang, Xin; Rosa, Guilherme Jm; Radunz, Amy E; Khatib, Hasan

2014-11-28

Maternal nutrition during different stages of pregnancy can induce significant changes in the structure, physiology, and metabolism of the offspring. These changes could have important implications on food animal production especially if these perturbations impact muscle and adipose tissue development. Here, we evaluated the impact of different maternal isoenergetic diets, alfalfa haylage (HY; fiber), corn (CN; starch), and dried corn distillers grains (DG; fiber plus protein plus fat), on the transcriptome of fetal muscle and adipose tissues in sheep. Prepartum diets were associated with notable gene expression changes in fetal tissues. In longissimus dorsi muscle, a total of 224 and 823 genes showed differential expression (FDR ≤0.05) in fetuses derived from DG vs. CN and HY vs. CN maternal diets, respectively. Several of these significant genes affected myogenesis and muscle differentiation. In subcutaneous and perirenal adipose tissues, 745 and 208 genes were differentially expressed (FDR ≤0.05), respectively, between CN and DG diets. Many of these genes are involved in adipogenesis, lipogenesis, and adipose tissue development. Pathway analysis revealed that several GO terms and KEGG pathways were enriched (FDR ≤0.05) with differentially expressed genes associated with tissue and organ development, chromatin biology, and different metabolic processes. These findings provide evidence that maternal nutrition during pregnancy can alter the programming of fetal muscle and fat tissues in sheep. The ramifications of the observed gene expression changes, in terms of postnatal growth, body composition, and meat quality of the offspring, warrant future investigation.

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells.

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Eoh, Joon H; Shen, Nian; Burke, Jacqueline A; Hinderer, Svenja; Xia, Zhiyong; Schenke-Layland, Katja; Gerecht, Sharon

2017-04-01

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have

The Muscle Metabolome Differs between Healthy and Frail Older Adults.

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Fazelzadeh, Parastoo; Hangelbroek, Roland W J; Tieland, Michael; de Groot, Lisette C P G M; Verdijk, Lex B; van Loon, Luc J C; Smilde, Age K; Alves, Rodrigo D A M; Vervoort, Jacques; Müller, Michael; van Duynhoven, John P M; Boekschoten, Mark V

2016-02-05

Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects, and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference group. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies.

Tissue-specific stem cells: Lessons from the skeletal muscle satellite cell

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Brack, Andrew S.; Rando, Thomas A.

2012-01-01

In 1961, the satellite cell was first identified when electron microscopic examination of skeletal muscle demonstrated a cell wedged between the plasma membrane of the muscle fiber and the basement membrane. In recent years it has been conclusively demonstrated that the satellite cell is the primary cellular source for muscle regeneration and is equipped with the potential to self renew, thus functioning as a bone fide skeletal muscle stem cell (MuSC). As we move past the 50th anniversary of the satellite cell, we take this opportunity to discuss the current state of the art and dissect the unknowns in the MuSC field. PMID:22560074

Hypoxia Enhances Differentiation of Adipose Tissue-Derived Stem Cells toward the Smooth Muscle Phenotype

Directory of Open Access Journals (Sweden)

Fang Wang

2018-02-01

Full Text Available Smooth muscle differentiated adipose tissue-derived stem cells are a valuable resource for regeneration of gastrointestinal tissues, such as the gut and sphincters. Hypoxia has been shown to promote adipose tissue-derived stem cells proliferation and maintenance of pluripotency, but the influence of hypoxia on their smooth myogenic differentiation remains unexplored. This study investigated the phenotype and contractility of adipose-derived stem cells differentiated toward the smooth myogenic lineage under hypoxic conditions. Oxygen concentrations of 2%, 5%, 10%, and 20% were used during differentiation of adipose tissue-derived stem cells. Real time reverse transcription polymerase chain reaction and immunofluorescence staining were used to detect the expression of smooth muscle cells-specific markers, including early marker smooth muscle alpha actin, middle markers calponin, caldesmon, and late marker smooth muscle myosin heavy chain. The specific contractile properties of cells were verified with both a single cell contraction assay and a gel contraction assay. Five percent oxygen concentration significantly increased the expression levels of α-smooth muscle actin, calponin, and myosin heavy chain in adipose-derived stem cell cultures after 2 weeks of induction (p < 0.01. Cells differentiated in 5% oxygen conditions showed greater contraction effect (p < 0.01. Hypoxia influences differentiation of smooth muscle cells from adipose stem cells and 5% oxygen was the optimal condition to generate smooth muscle cells that contract from adipose stem cells.

Levels of arsenic, cadmium, lead and mercury in the branchial plate and muscle tissue of mobulid rays

International Nuclear Information System (INIS)

Ooi, Michelle S.M.; Townsend, Kathy A.; Bennett, Michael B.; Richardson, Anthony J.; Fernando, Daniel; Villa, Cesar A.; Gaus, Caroline

2015-01-01

Highlights: • Branchial plate and muscle tissue from mobulid rays were analysed for certain metals. • Mean concentrations of cadmium in Mobula japanica were above the EC ML. • Mean inorganic arsenic concentration in Mobula japanica muscle equalled the FSANZ ML. • Mean concentration of lead in Manta alfredi muscle tissue exceeded EC and Codex MLs. • There were significant correlations between the types of tissues for some metals. - Abstract: Mobulid rays are targeted in fisheries for their branchial plates, for use in Chinese medicine. Branchial plate and muscle tissue from Mobula japanica were collected from fish markets in Sri Lanka, and muscle tissue biopsies from Manta alfredi in Australia. These were analysed for arsenic, cadmium, lead and mercury and compared to maximum levels (MLs) set by Food Standards Australia and New Zealand (FSANZ), European Commission (EC) and Codex Alimentarius Commission. The estimated intake for a vulnerable human age group was compared to minimal risk levels set by the Agency for Toxic Substances and Disease Registry. The mean inorganic arsenic concentration in M. japanica muscle was equivalent to the FSANZ ML while cadmium exceeded the EC ML. The mean concentration of lead in M. alfredi muscle tissue exceeded EC and Codex MLs. There were significant positive linear correlations between branchial plate and muscle tissue concentrations for arsenic, cadmium and lead

Meet the new meat: tissue engineered skeletal muscle

NARCIS (Netherlands)

Langelaan, M.L.P.; Boonen, K.J.M.; Polak, R.B.; Baaijens, F.P.T.; Post, M.J.; Schaft, van der D.W.J.

2010-01-01

Contemporary large-scale farming and transportation of livestock brings along a high risk of infectious animal diseases and environmental burden through greenhouse gas emission. A new approach to produce meat and thereby reducing these risks is found in tissue engineering of skeletal muscle. This

Not just quantity: gluteus maximus muscle characteristics in able-bodied and SCI individuals--implications for tissue viability.

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Wu, Gary A; Bogie, Kath M

2013-08-01

Some individuals with spinal cord injury (SCI) remain pressure ulcer (PU) free whilst others experience a recurring cycle of tissue breakdown. Detailed analysis of gluteal muscle characteristics may provide insights to local tissue viability variability. The study hypothesis was that SCI individuals have altered muscle composition compared to able-bodied (AB). Ten AB and ten SCI received a supine pelvic CT scan, with contrast. Cross-sectional area (CSA) and overall muscle volume were derived using image analysis. Gluteal muscle tissue type was classified at the S2/S3 sacral vertebrae midpoint, the superior greater trochanters margin (GT) and the inferior ischial tuberosities margin (IT) using the linear transformation Hounsfield Unit scale. SCI gluteal CSA was less than for AB throughout the muscle, with the greatest relative atrophy at the IT (48%). Average AB gluteal volume was nearly double SCI. Eight SCI had over 20% infiltrative adipose tissue, three with over 50%. SCI gluteal CSA and intramuscular fat infiltration were significantly negatively correlated (p SCI IT axial slices showed less lean muscle and higher intramuscular fat infiltration than more proximally (p SCI gluteal muscle characteristics were indicative of impaired tissue viability. SCI disuse muscle atrophy was anticipated; the analytic approach further indicated that intramuscular atrophy was not uniform. SCI muscle composition showed increased proportions of both low density muscle and adipose tissue. CT scan with contrast is effective for gluteal muscle characterization. This assessment technique may contribute to determination of personalized risk for PU development and other secondary complications. Published by Elsevier Ltd.

Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors.

Science.gov (United States)

Ansari, Sahar; Chen, Chider; Xu, Xingtian; Annabi, Nasim; Zadeh, Homayoun H; Wu, Benjamin M; Khademhosseini, Ali; Shi, Songtao; Moshaverinia, Alireza

2016-06-01

Repair and regeneration of muscle tissue following traumatic injuries or muscle diseases often presents a challenging clinical situation. If a significant amount of tissue is lost the native regenerative potential of skeletal muscle will not be able to grow to fill the defect site completely. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material, present an advantageous alternative therapeutic option for muscle tissue engineering in comparison to current treatment modalities available. To date, there has been no report on application of gingival mesenchymal stem cells (GMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of the current study were to develop an injectable 3D RGD-coupled alginate scaffold with multiple growth factor delivery capacity for encapsulating GMSCs, and to evaluate the capacity of encapsulated GMSCs to differentiate into myogenic tissue in vitro and in vivo where encapsulated GMSCs were transplanted subcutaneously into immunocompromised mice. The results demonstrate that after 4 weeks of differentiation in vitro, GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited muscle cell-like morphology with high levels of mRNA expression for gene markers related to muscle regeneration (MyoD, Myf5, and MyoG) via qPCR measurement. Our quantitative PCR analyzes revealed that the stiffness of the RGD-coupled alginate regulates the myogenic differentiation of encapsulated GMSCs. Histological and immunohistochemical/fluorescence staining for protein markers specific for myogenic tissue confirmed muscle regeneration in subcutaneous transplantation in our in vivo animal model. GMSCs showed significantly greater capacity for myogenic regeneration in comparison to hBMMSCs (p alginate hydrogel with multiple growth factor delivery capacity is a promising candidate for muscle tissue engineering.

Mechanic effect of pulsed focused ultrasound in tumor and muscle tissue evaluated by MRI, histology, and microarray analysis

International Nuclear Information System (INIS)

Hundt, Walter; Yuh, Esther L.; Steinbach, Silke; Bednarski, Mark D.; Guccione, Samira

2010-01-01

The purpose of this study was to investigate the effect of pulsed high-intensity focused ultrasound (HIFU) to tumor and muscle tissue. Pulsed HIFU was applied to tumor and muscle tissue in C3H/Km mice. Three hours after HIFU treatment pre- and post-contrast T1-wt, T2-wt images and a diffusion-wt STEAM-sequence were obtained. After MR imaging, the animals were euthenized and the treated tumor and muscle was taken out for histology and functional genomic analysis. In the tumor tissue a slight increase of the diffusion coefficient could be found. In the muscle tissue T2 images showed increased signal intensity and post-contrast T1 showed a decreased contrast uptake in the center and a severe contrast uptake in the surrounding muscle tissue. A significant increase of the diffusion coefficient was found. Gene expression analysis revealed profound changes in the expression levels of 29 genes being up-regulated and 3 genes being down-regulated in the muscle tissue and 31 genes being up-regulated and 15 genes being down-regulated in the SCCVII tumor tissue. Seven genes were up-regulated in both tissue types. The highest up-regulated gene in the tumor and muscle tissue encoded for Mouse histone H2A.1 gene (FC = 13.2 ± 20.6) and Apolipoprotein E (FC = 12.8 ± 27.4) respectively MHC class III (FC = 83.7 ± 67.4) and hsp70 (FC = 75.3 ± 85.0). Immunoblot confirmed the presence of HSP70 protein in the muscle tissue. Pulsed HIFU treatment on tumor and muscle tissue results in dramatic changes in gene expression, indicating that the effect of pulsed HIFU is in some regard dependent and also independent of the tissue type.

Creating Interactions between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System.

Science.gov (United States)

Smith, Alec S T; Passey, Samantha L; Martin, Neil R W; Player, Darren J; Mudera, Vivek; Greensmith, Linda; Lewis, Mark P

2016-01-01

Effective models of mammalian tissues must allow and encourage physiologically (mimetic) correct interactions between co-cultured cell types in order to produce culture microenvironments as similar as possible to those that would normally occur in vivo. In the case of skeletal muscle, the development of such a culture model, integrating multiple relevant cell types within a biomimetic scaffold, would be of significant benefit for investigations into the development, functional performance, and pathophysiology of skeletal muscle tissue. Although some work has been published regarding the behaviour of in vitro muscle models co-cultured with organotypic slices of CNS tissue or with stem cell-derived neurospheres, little investigation has so far been made regarding the potential to maintain isolated motor neurons within a 3D biomimetic skeletal muscle culture platform. Here, we review the current state of the art for engineering neuromuscular contacts in vitro and provide original data detailing the development of a 3D collagen-based model for the co-culture of primary muscle cells and motor neurons. The devised culture system promotes increased myoblast differentiation, forming arrays of parallel, aligned myotubes on which areas of nerve-muscle contact can be detected by immunostaining for pre- and post-synaptic proteins. Quantitative RT-PCR results indicate that motor neuron presence has a positive effect on myotube maturation, suggesting neural incorporation influences muscle development and maturation in vitro. The importance of this work is discussed in relation to other published neuromuscular co-culture platforms along with possible future directions for the field. © 2016 S. Karger AG, Basel.

Meat Science and Muscle Biology Symposium: manipulating meat tenderness by increasing the turnover of intramuscular connective tissue.

Science.gov (United States)

Purslow, P P; Archile-Contreras, A C; Cha, M C

2012-03-01

Controlled reduction of the connective tissue contribution to cooked meat toughness is an objective that would have considerable financial impact in terms of added product value. The amount of intramuscular connective tissue in a muscle appears connected to its in vivo function, so reduction of the overall connective tissue content is not thought to be a viable target. However, manipulation of the state of maturity of the collagenous component is a biologically viable target; by increasing connective tissue turnover, less mature structures can be produced that are functional in vivo but more easily broken down on cooking at temperatures above 60°C, thus improving cooked meat tenderness. Recent work using cell culture models of fibroblasts derived from muscle and myoblasts has identified a range of factors that alter the activity of the principal enzymes responsible for connective tissue turnover, the matrix metalloproteinases (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same animal show different cell proliferation and MMP activity, which may relate to the different connective tissue content and architecture in functionally different muscles. Expression of MMP by fibroblasts is increased by vitamins that can counter the negative effects of oxidative stress on new collagen synthesis. Preliminary work using in situ zymography of myotubes in culture also indicates increased MMP activity in the presence of epinephrine and reactive oxidative species. Comparison of the relative changes in MMP expression from muscle cells vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli. Muscle cells are likely to produce more of the total MMP in muscle tissue as a whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary between oxidative and glycolytic muscle fibers within the same muscle. The implication is that the different muscle fiber composition of different muscles eaten as meat may influence the

Modeling microwave electromagnetic field absorption in muscle tissues

Science.gov (United States)

Felbacq, D.; Clerjon, S.; Damez, J. L.; Zolla, F.

2002-07-01

Absorption of electromagnetic energy in human tissues is an important issue with respect to the safety of low-level exposure. Simulation is a way to a better understanding of electromagnetic dosimetry. This letter presents a comparison between results obtained from a numerical simulation and experimental data of absorbed energy by a muscle. Simulation was done using a bidimensional double-scale homogenization scheme leading to the effective permittivity tensor. Experimental measurements were performed at 10 GHz on bovine muscle, 30 hours after slaughter, thanks to the open-ended rectangular waveguide method. Results show a good agreement between measurements and simulated data.

Engineering skeletal muscle tissues from murine myoblast progenitor cells and application of electrical stimulation

NARCIS (Netherlands)

Schaft, van der D.W.J.; Spreeuwel, van A.C.C.; Boonen, K.J.M.; Langelaan, M.L.P.; Bouten, C.V.C.; Baaijens, F.P.T.

2013-01-01

Engineered muscle tissues can be used for several different purposes, which include the production of tissues for use as a disease model in vitro, e.g. to study pressure ulcers, for regenerative medicine and as a meat alternative 1. The first reported 3D muscle constructs have been made many years

Relationships of mercury concentrations across tissue types, muscle regions and fins for two shark species

KAUST Repository

O'Bryhim, Jason R.

2017-01-31

Mercury (Hg) exposure poses a threat to both fish and human health. Sharks are known to bioaccumulate Hg, however, little is known regarding how Hg is distributed between different tissue groups (e.g. muscle regions, organs). Here we evaluated total mercury (THg) concentrations from eight muscle regions, four fins (first dorsal, left and right pectorals, caudal-from both the inner core and trailing margin of each fin), and five internal organs (liver, kidney, spleen, heart, epigonal organ) from two different shark species, bonnethead (Sphyrna tiburo) and silky shark (Carcharhinus falciformis) to determine the relationships of THg concentrations between and within tissue groups. Total Hg concentrations were highest in the eight muscle regions with no significant differences in THg concentrations between the different muscle regions and muscle types (red and white). Results from tissue collected from any muscle region would be representative of all muscle sample locations. Total Hg concentrations were lowest in samples taken from the fin inner core of the first dorsal, pectoral, and caudal (lower lobe) fins. Mercury concentrations for samples taken from the trailing margin of the dorsal, pectoral, and caudal fins (upper and lower lobe) were also not significantly different from each other for both species. Significant relationships were found between THg concentrations in dorsal axial muscle tissue and the fin inner core, liver, kidney, spleen and heart for both species as well as the THg concentrations between the dorsal fin trailing margin and the heart for the silky shark and all other sampled tissue types for the bonnethead shark. Our results suggest that biopsy sampling of dorsal muscle can provide data that can effectively estimate THg concentrations in specific organs without using more invasive, or lethal methods.

Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension.

Science.gov (United States)

Nyberg, M; Mortensen, S P; Hellsten, Y

2013-03-01

Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

DEFF Research Database (Denmark)

Mulla, N A; Simonsen, L; Bülow, J

2000-01-01

, a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease......One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid...... metabolism during a 3 h post-exercise period. Six subjects were studied twice. In one experiment, they exercised for 90 min at 40% of maximal O2 consumption (VO2,max) and in the other experiment they exercised at 60% VO2,max for 60 min. For both experiments, catheters were inserted in an artery...

A Simplified Method for Tissue Engineering Skeletal Muscle Organoids in Vitro

Science.gov (United States)

Shansky, Janet; DelTatto, Michael; Chromiak, Joseph; Vandenburgh, Herman

1996-01-01

Tissue-engineered three dimensional skeletal muscle organ-like structures have been formed in vitro from primary myoblasts by several different techniques. This report describes a simplified method for generating large numbers of muscle organoids from either primary embryonic avian or neonatal rodent myoblasts, which avoids the requirements for stretching and other mechanical stimulation.

Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

Science.gov (United States)

Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

2018-06-01

 Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

Gene Expression and DNA Methylation of PPARGC1A in Muscle and Adipose Tissue From Adult Offspring of Women With Diabetes in Pregnancy

DEFF Research Database (Denmark)

Kelstrup, Louise; Hjort, Line; Houshmand-Øregaard, Azadeh

2016-01-01

) and of women from the background population (O-BP) using a clinical examination, oral glucose tolerance test, and gene expression and DNA methylation of PPARGC1A in skeletal muscle and SAT. Plasma glucose was significantly higher for both O-GDM and O-T1D compared with O-BP (P expression...... in muscle was lower in O-GDM compared with O-BP (P = 0.0003), whereas no differences were found between O-T1D and O-BP in either tissue. PPARGC1A DNA methylation percentages in muscle and SAT were similar among all groups. Decreased PPARGC1A gene expression in muscle has previously been associated...... with abnormal insulin function and may thus contribute to the increased risk of metabolic disease in O-GDM. The unaltered PPARGC1A gene expression in muscle of O-T1D suggests that factors other than intrauterine hyperglycemia may contribute to the decreased PPARGC1A expression in O-GDM....

Automated segmentation of muscle and adipose tissue on CT images for human body composition analysis

Science.gov (United States)

Chung, Howard; Cobzas, Dana; Birdsell, Laura; Lieffers, Jessica; Baracos, Vickie

2009-02-01

The ability to compute body composition in cancer patients lends itself to determining the specific clinical outcomes associated with fat and lean tissue stores. For example, a wasting syndrome of advanced disease associates with shortened survival. Moreover, certain tissue compartments represent sites for drug distribution and are likely determinants of chemotherapy efficacy and toxicity. CT images are abundant, but these cannot be fully exploited unless there exist practical and fast approaches for tissue quantification. Here we propose a fully automated method for segmenting muscle, visceral and subcutaneous adipose tissues, taking the approach of shape modeling for the analysis of skeletal muscle. Muscle shape is represented using PCA encoded Free Form Deformations with respect to a mean shape. The shape model is learned from manually segmented images and used in conjunction with a tissue appearance prior. VAT and SAT are segmented based on the final deformed muscle shape. In comparing the automatic and manual methods, coefficients of variation (COV) (1 - 2%), were similar to or smaller than inter- and intra-observer COVs reported for manual segmentation.

Methods for demonstration of enzyme activity in muscle fibres at the muscle/bone interface in demineralized tissue

DEFF Research Database (Denmark)

Kirkeby, S; Vilmann, H

1981-01-01

A method for demonstration of activity for ATPase and various oxidative enzymes (succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase) in muscle/bone sections of fixed and demineralized tissue has been developed. It was found that it is possible to preserve...... considerable amounts of the above mentioned enzymes in the muscle fibres at the muscle/bone interfaces. The best results were obtained after 20 min fixation, and 2-3 weeks of storage in MgNa2EDTA containing media. As the same technique previously has been used to describe patterns of resorption and deposition...

Finite-element simulation of blood perfusion in muscle tissue during compression and sustained contraction.

Science.gov (United States)

Vankan, W J; Huyghe, J M; Slaaf, D W; van Donkelaar, C C; Drost, M R; Janssen, J D; Huson, A

1997-09-01

Mechanical interaction between tissue stress and blood perfusion in skeletal muscles plays an important role in blood flow impediment during sustained contraction. The exact mechanism of this interaction is not clear, and experimental investigation of this mechanism is difficult. We developed a finite-element model of the mechanical behavior of blood-perfused muscle tissue, which accounts for mechanical blood-tissue interaction in maximally vasodilated vasculature. Verification of the model was performed by comparing finite-element results of blood pressure and flow with experimental measurements in a muscle that is subject to well-controlled mechanical loading conditions. In addition, we performed simulations of blood perfusion during tetanic, isometric contraction and maximal vasodilation in a simplified, two-dimensional finite-element model of a rat calf muscle. A vascular waterfall in the venous compartment was identified as the main cause for blood flow impediment both in the experiment and in the finite-element simulations. The validated finite-element model offers possibilities for detailed analysis of blood perfusion in three-dimensional muscle models under complicated loading conditions.

Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue

NARCIS (Netherlands)

Gallagher, D.; Kuznia, P.; Heshka, S.; Albu, J.; Heymsfield, S.B.; Goodpaster, B.H.; Visser, M.; Harris, T.B.

2005-01-01

BACKGROUND: The manner in which fat depot volumes and distributions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. OBJECTIVE: The objective was to quantify a previously unstudied and novel intermuscular AT (IMAT) depot and subcutaneous AT, visceral AT (VAT), and

The comparative morphology of the muscle tissues and changes in constituents in the pig types.

Science.gov (United States)

Fehér, G; Fazekas, S; Sándor, I; Kollár, N

1990-09-01

The authors have revealed the main value characteristics of pork production by testing in five different types of pig the volume of contractile and collagen proteins, that of proteoglycans, the constituents of blood and the enzymes of the blood plasma. The contractile proteins of the muscle tissues basically determine the quality of pork. The same applies to the water retention capacity, colloidal characteristics and glycogen content of meat. The amount of contractile proteins has decreased in the best meat producing types of pig. Parallel with the decrease of white meat, and with the increase in the volume of ham, chop and chuck the contractile protein content of muscles decreased. The scientific fact according to which there is a certain correlation among the changes in the volume of contractile proteins, blood sugar level, blood serum CPK and the intensity of activity of the LDH enzymes promotes the qualifying of live animals and the work of the geneticists aiming at the increasing of the contractile protein content of the muscle tissues of pigs by selection. According to tests carried out by us the primary cause of PSE changes is a decreased volume of contractile proteins. Increased stress sensitivity and all the other factors have but a secondary importance and are all consequential. The decrease in the quantity of contractile proteins or--it is better to put it this way--the lack of the proper amount of such proteins characterizing a fully developed pig's organism is caused by the nowadays usual breeding technologies and can be well explained by those selection activities which aim at a one-sided kind of pork production.

Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle,

Directory of Open Access Journals (Sweden)

Samanta Portão de Carlos

2014-08-01

Full Text Available OBJECTIVE: To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively] in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS for 7, 15, 30, 45, or 60 days. METHODS: Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group: a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively. RESULTS: Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice, the greatest differences (increases in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle. CONCLUSION: Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD.

Fatty acid composition of muscle and heart tissue of Nile perch ...

African Journals Online (AJOL)

The fatty acid composition in the heart tissue and muscle tissue of the Nile perch, Lates niloticus, and Nile tilapia, Oreochromis niloticus populations from Lakes Kioga and Victoria was determined by methanolysis and gas chromatography of the resulting fatty acid methyl esters. The analytical data were treated by ...

Study of the response of the penile corporal tissue and cavernosus muscles to micturition

Directory of Open Access Journals (Sweden)

El Sibai Olfat

2008-03-01

Full Text Available Abstract Background The reaction of the corpora cavernosa (CC, the corpus spongiosum (CS, the bulbocavernosus (BCM and ischiocavernosus (ICM muscles to passage of urine through the urethra during micturition is not known. We investigated the hypothesis that the passage of urine through the urethra stimulates the corporal tissue and cavernosus muscles. Methods In 30 healthy men (mean age 42.8 ± 11.7 years, the electromyographic activity (EMG of the CC, CS, BCM, and ICM were recorded before and during micturition, and on interruption of and straining during micturition. These tests were repeated after individual anesthetization of urethra, corporal tissue, and cavernosus muscles. Results During micturition, the slow wave variables (frequency, amplitude, conduction velocity of the CC and CS decreased while the motor unit action potentials of the BCM and ICM increased; these EMG changes were mild and returned to the basal values on interruption or termination of micturition. Micturition after individual anesthetization of urethra, corporal tissue and cavernosal muscles did not effect significant EMG changes in these structures, while saline administration produced changes similar to those occurring before saline administration. Conclusion The decrease of sinusoidal and increase of cavernosus muscles' EMG activity during micturition apparently denotes sinusoidal relaxation and cavernosus muscles contraction. Sinusoidal muscle relaxation and cavernosus muscles contraction upon micturition are suggested to be mediated through a 'urethro-corporocavernosal reflex'. These sinusoidal and cavernosus muscle changes appear to produce a mild degree of penile tumescence and stretch which might assist in urinary flow during micturition.

Two-layer tissue engineered urethra using oral epithelial and muscle derived cells.

Science.gov (United States)

Mikami, Hiroshi; Kuwahara, Go; Nakamura, Nobuyuki; Yamato, Masayuki; Tanaka, Masatoshi; Kodama, Shohta

2012-05-01

We fabricated novel tissue engineered urethral grafts using autologously harvested oral cells. We report their viability in a canine model. Oral tissues were harvested by punch biopsy and divided into mucosal and muscle sections. Epithelial cells from mucosal sections were cultured as epithelial cell sheets. Simultaneously muscle derived cells were seeded on collagen mesh matrices to form muscle cell sheets. At 2 weeks the sheets were joined and tubularized to form 2-layer tissue engineered urethras, which were autologously grafted to surgically induced urethral defects in 10 dogs in the experimental group. Tissue engineered grafts were not applied to the induced urethral defect in control dogs. The dogs were followed 12 weeks postoperatively. Urethrogram and histological examination were done to evaluate the grafting outcome. We successfully fabricated 2-layer tissue engineered urethras in vitro and transplanted them in dogs in the experimental group. The 12-week complication-free rate was significantly higher in the experimental group than in controls. Urethrogram confirmed urethral patency without stricture in the complication-free group at 12 weeks. Histologically urethras in the transplant group showed a stratified epithelial layer overlying well differentiated submucosa. In contrast, urethras in controls showed severe fibrosis without epithelial layer formation. Two-layer tissue engineered urethras were engineered using cells harvested by minimally invasive oral punch biopsy. Results suggest that this technique can encourage regeneration of a functional urethra. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effect of heat stress on contractility of tissue-engineered artificial skeletal muscle.

Science.gov (United States)

Takagi, Shunya; Nakamura, Tomohiro; Fujisato, Toshia

2018-01-23

The effects of heat stress on tissue like skeletal muscle have been widely studied. However, the mechanism responsible for the effect of heat stress is still unclear. A useful experimental tissue model is necessary because muscle function in cell culture may differ from native muscle and measuring its contractility is difficult. We previously reported three-dimensional tissue-engineered artificial skeletal muscle (TEM) that can be easily set in a measurement apparatus for quantitative evaluation of contractility. We have now applied TEM to the investigation of heat stress. We analyzed contractility immediately after thermal exposure at 39 °C for 24 or 48 h to evaluate the acute effects and after thermal exposure followed by normal culture to evaluate the aftereffects. Peak twitch contractile force and time-to-peak twitch were used as contractile parameters. Heat stress increased the TCF in the early stage (1 week) after normal culture; the TCF decreased temporarily in the middle to late stages (2-3 weeks). These results suggest that heat stress may affect both myoblast fusion and myotube differentiation in the early stage of TEM culture, but not myotube maturation in the late stage. The TCF increase rate with thermal exposure was significantly higher than that without thermal exposure. Although detailed analysis at the molecular level is necessary for further investigation, our artificial skeletal muscle may be a promising tool for heat stress investigation.

Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas

Energy Technology Data Exchange (ETDEWEB)

Veld, Joyce; Vossen, Josephina A.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); De Amorim Bernstein, Karen [Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Francis H Burr Proton Therapy Center, Boston, MA (United States); Halpern, Elkan F. [Massachusetts General Hospital and Harvard Medical School, Institute of Technology Assessment, Boston, MA (United States)

2016-12-15

To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. (orig.)

Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas

International Nuclear Information System (INIS)

Veld, Joyce; Vossen, Josephina A.; Torriani, Martin; Bredella, Miriam A.; De Amorim Bernstein, Karen; Halpern, Elkan F.

2016-01-01

To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. (orig.)

Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

Science.gov (United States)

Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

1999-01-01

Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

Science.gov (United States)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Selection, processing and clinical application of muscle-skeletal tissue; Seleccion, Procesamiento y Aplicacion Clinica de Tejido Musculo-Esqueletico

Energy Technology Data Exchange (ETDEWEB)

Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G. [ININ, Carretera Mexico-Toluca s/n, 52750 La Marquesa, Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: dlz@nuclear.inin. mx

2007-07-01

Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.

Directory of Open Access Journals (Sweden)

Tingqing Guo

Full Text Available Myostatin (Mstn is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn(-/- mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/- mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn(-/- mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn(-/- mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn(-/- mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/- mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes.

In vitro terahertz monitoring of muscle tissue dehydration under the action of hyperosmotic agents

Energy Technology Data Exchange (ETDEWEB)

Kolesnikov, A S; Kolesnikova, E A; Popov, A P; Tuchin, V V [N.G. Chernyshevsky Saratov State University, Saratov (Russian Federation); Nazarov, M M [Institute on Laser and Information Technologies, Russian Academy of Sciences, Shatura, Moscow Region (Russian Federation); Shkurinov, A P [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation)

2014-07-31

Dehydration of muscle tissue in vitro under the action of biologically compatible hyperosmotic agents is studied using a laser terahertz spectrometer in the frequency range from 0.25 to 2.5 THz. Broadband terahertz absorption and reflection spectra of the bovine skeletal muscle tissue were obtained under the action of glycerol, polyethylene glycol with the molecular weight 600 (PEG-600), and propylene glycol. The presented results are proposed for application in developing the methods of image contrast enhancement and increasing the depth of biological tissue probing with terahertz radiation. (laser biophotonics)

Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

2013-01-01

performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. CONCLUSION: Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes......AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. METHODS: In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study...

GLUT4 expression at the plasma membrane is related to fibre volume in human skeletal muscle fibres

DEFF Research Database (Denmark)

Gaster, M; Vach, W; Beck-Nielsen, H

2002-01-01

In this study we examined the relationship between GLUT4 expression at the plasma membrane and muscle fibre size in fibre-typed human muscle fibres by immunocytochemistry and morphometry in order to gain further insight into the regulation of GLUT4 expression. At the site of the plasma membrane...

Tissue clearing for confocal imaging of native and bio-artificial skeletal muscle.

Science.gov (United States)

Decroix, L; Van Muylder, V; Desender, L; Sampaolesi, M; Thorrez, L

2015-01-01

Novel clearing techniques have revolutionized three-dimensional confocal imaging of the brain without the need for physical tissue sectioning. We evaluated three clearing methods, ScaleA2, Clear(T2), and 3DISCO for visualizing native and tissue engineered muscle by confocal microscopy. We found that Clear(T2) treatment improved the depth of visualization of immunohistochemical staining slightly, but did not improve depth of visualization of endogenous green fluorescent protein (GFP). ScaleA2 preserved endogenous GFP signal better and permitted significantly deeper GFP imaging, but it was incompatible with tropomyosin immunohistochemical staining. 3DISCO treatment preserved both endogenous GFP and immunohistochemical staining, and permitted significantly deeper imaging. Clearing time for the 3DISCO procedure is short compared to ScaleA2 and Clear(T2). We suggest that 3DISCO is the preferable clearing method for native and tissue engineered skeletal muscle tissue.

Muscle contraction increases carnitine uptake via translocation of OCTN2

Energy Technology Data Exchange (ETDEWEB)

Furuichi, Yasuro [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan); Sugiura, Tomoko; Kato, Yukio [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan); Takakura, Hisashi [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan); Hanai, Yoshiteru [Nagoya Institute of Technology, Nagoya (Japan); Hashimoto, Takeshi [Ritsumeikan University, Kusatsu (Japan); Masuda, Kazumi, E-mail: masuda@ed.kanazawa-u.ac.jp [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)

2012-02-24

Highlights: Black-Right-Pointing-Pointer Muscle contraction augmented carnitine uptake into rat hindlimb muscles. Black-Right-Pointing-Pointer An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. Black-Right-Pointing-Pointer Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. Black-Right-Pointing-Pointer OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL{sub uptake}) of L-[{sup 3}H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL{sub uptake} of [{sup 14}C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL{sub uptake} of L-[{sup 3}H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p < 0.05). The CL{sub uptake} of [{sup 14}C]IAP was much higher than that of L-[{sup 3}H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly

Muscle contraction increases carnitine uptake via translocation of OCTN2

International Nuclear Information System (INIS)

Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

2012-01-01

Highlights: ► Muscle contraction augmented carnitine uptake into rat hindlimb muscles. ► An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. ► Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. ► OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL uptake ) of L-[ 3 H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL uptake of [ 14 C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL uptake of L-[ 3 H]carnitine in the contracting muscles increased 1.4–1.7-fold as compared to that in the contralateral resting muscles (p uptake of [ 14 C]IAP was much higher than that of L-[ 3 H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

Trace metal concentrations in edible muscle tissues of some locally marketed fish

International Nuclear Information System (INIS)

Ansari, T.M.; Ichokitar, M.Y.; Ashraf, M.

2000-01-01

Edible muscle tissues of five fish species marketed in Multan, i.e., Rohu (Labeo rohita). (Labeo calhasu). Mori (cirrina inrigala). Ichagga (Rita rita) and Singliaree (mystus (osteobagrus) nor) have been analyzed quantitatively for trace elements, essential as well as toxic, using flame atomic absorption spectrometry. Dry ashing procedure has been employed to prepare sample solutions. Result indicate that edible muscle tissue of these fish, in general, contain higher amounts of potassium, calcium, sodium and magnesium, moderate quantities of zinc and iron and lessor amounts of copper and manganese. However, cadmium and lead were found to be below the limit of detection. (author)

Change in refractive index of muscle tissue during laser-induced interstitial thermotherapy.

Science.gov (United States)

Chen, Na; Chen, Meimei; Liu, Shupeng; Guo, Qiang; Chen, Zhenyi; Wang, Tingyun

2014-01-01

This paper presents a long-period fiber-grating (LPG) based Michelson interferometric refractometry to monitor the change in refractive index of porcine muscle during laser-induced interstitial thermotherapy (LITT). As the wavelength of RI interferometer alters with the change in refractive index around the probe, the LPG based refractometry is combined with LITT system to measure the change in refractive index of porcine muscle when irradiated by laser. The experimental results show the denaturation of tissue alters the refractive index significantly and the LPG sensor can be applied to monitor the tissue state during the LITT.

Plasma and muscle cortisol measurements as indicators of meat quality and stress in pigs.

Science.gov (United States)

Shaw, F D; Trout, G R; McPhee, C P

1995-01-01

Post-slaughter blood samples and muscle samples were collected from pigs slaughtered at the completion of a live-animal performance trial. There were two lines of pigs in which the halothane allele (n) was segregating. The lines were a lean line selected for rapid lean growth and an unselected fat line. There were homozygous normal (NN), homozygous halothane positive (nn) and heterozygous (Nn) genotypes in both lnes. Cortisol was measured in the plasma of the blood samples and in muscle juice obtained by high-speed centrifugation. Meat quality was assessed using pH, colour, fibre-optic probe, drip loss and cure yield measurements. Plasma cortisol concentrations in the fat line were significantly (P meat quality attributes were generally highly significant (r = 0·31 to r = 0·51, P < 0·001) There was a highly significant correlation (r = 0·73, P < 0·0001) between plasma and muscle cortisol concentrations.

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

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Sara Martina Maffioletti

2018-04-01

Full Text Available Summary: Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. : Maffioletti et al. generate human 3D artificial skeletal muscles from healthy donors and patient-specific pluripotent stem cells. These human artificial muscles accurately model severe genetic muscle diseases. They can be engineered to include other cell types present in skeletal muscle, such as vascular cells and motor neurons. Keywords: skeletal muscle, pluripotent stem cells, iPS cells, myogenic differentiation, tissue engineering, disease modeling, muscular dystrophy, organoids

Effects of heat stimulation and l-ascorbic acid 2-phosphate supplementation on myogenic differentiation of artificial skeletal muscle tissue constructs.

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Ikeda, Kazushi; Ito, Akira; Sato, Masanori; Kanno, Shota; Kawabe, Yoshinori; Kamihira, Masamichi

2017-05-01

Although skeletal muscle tissue engineering has been extensively studied, the physical forces produced by tissue-engineered skeletal muscles remain to be improved for potential clinical utility. In this study, we examined the effects of mild heat stimulation and supplementation of a l-ascorbic acid derivative, l-ascorbic acid 2-phosphate (AscP), on myoblast differentiation and physical force generation of tissue-engineered skeletal muscles. Compared with control cultures at 37°C, mouse C2C12 myoblast cells cultured at 39°C enhanced myotube diameter (skeletal muscle hypertrophy), whereas mild heat stimulation did not promote myotube formation (differentiation rate). Conversely, AscP supplementation resulted in an increased differentiation rate but did not induce skeletal muscle hypertrophy. Following combined treatment with mild heat stimulation and AscP supplementation, both skeletal muscle hypertrophy and differentiation rate were enhanced. Moreover, the active tension produced by the tissue-engineered skeletal muscles was improved following combined treatment. These findings indicate that tissue culture using mild heat stimulation and AscP supplementation is a promising approach to enhance the function of tissue-engineered skeletal muscles. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

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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.

Infectivity of Trichinella spp. recovered from decaying mouse and fox muscle tissue

DEFF Research Database (Denmark)

Von Koller, J.; Kapel, C.M.O.; Enemark, Heidi L.

2001-01-01

The tolerance to degradation processes in meat of nine Trichinella genotypes was studied in mouse and fox tissue, respectively. Minced muscle tissue with Trichinella larvae of different age was stored at room temperature at 100 % relative humidity. During storage weekly sub samples of the minced...

Contribution of elastic tissues to the mechanics and energetics of muscle function during movement.

Science.gov (United States)

Roberts, Thomas J

2016-01-01

Muscle force production occurs within an environment of tissues that exhibit spring-like behavior, and this elasticity is a critical determinant of muscle performance during locomotion. Muscle force and power output both depend on the speed of contraction, as described by the isotonic force-velocity curve. By influencing the speed of contractile elements, elastic structures can have a profound effect on muscle force, power and work. In very rapid movements, elastic mechanisms can amplify muscle power by storing the work of muscle contraction slowly and releasing it rapidly. When energy must be dissipated rapidly, such as in landing from a jump, energy stored rapidly in elastic elements can be released more slowly to stretch muscle contractile elements, reducing the power input to muscle and possibly protecting it from damage. Elastic mechanisms identified so far rely primarily on in-series tendons, but many structures within muscles exhibit spring-like properties. Actomyosin cross-bridges, actin and myosin filaments, titin, and the connective tissue scaffolding of the extracellular matrix all have the potential to store and recover elastic energy during muscle contraction. The potential contribution of these elements can be assessed from their stiffness and estimates of the strain they undergo during muscle function. Such calculations provide boundaries for the possible roles these springs might play in locomotion, and may help to direct future studies of the uses of elastic elements in muscle. © 2016. Published by The Company of Biologists Ltd.

Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology.

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Hsiao, Amy Y; Okitsu, Teru; Onoe, Hiroaki; Kiyosawa, Mahiro; Teramae, Hiroki; Iwanaga, Shintaroh; Kazama, Tomohiko; Matsumoto, Taro; Takeuchi, Shoji

2015-01-01

The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D) cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT) cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments.

A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle.

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Hussey, Sophie E; Lum, Helen; Alvarez, Andrea; Cipriani, Yolanda; Garduño-Garcia, Jesús; Anaya, Luis; Dube, John; Musi, Nicolas

2014-03-01

Insulin-sensitive tissues (muscle, liver) of individuals with obesity and type 2 diabetes mellitus are in a state of low-grade inflammation, characterised by increased Toll-like receptor (TLR) expression and TLR-driven signalling. However, the cause of this mild inflammatory state is unclear. We tested the hypothesis that a prolonged mild increase in plasma NEFA will increase TLR expression and TLR-driven signalling (nuclear factor κB [NFκB] and mitogen-activated kinase [MAPK]) and impair insulin action in muscle of lean healthy individuals. Twelve lean, normal-glucose-tolerant participants were randomised to receive a 48 h infusion (30 ml/h) of saline or Intralipid followed by a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis muscle biopsies were performed before and during the clamp. Lipid infusion impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral insulin sensitivity (p < 0.01). The elevation in circulating NEFA increased expression of TLR3, TLR4 and TLR5, and several MAPK (MAPK8, MAP4K4, MAP2K3) and inhibitor of κB kinase-NFκB (CHUK [IKKA], c-REL [REL] and p65 [RELA, NFKB3, p65]) signalling genes (p < 0.05). The lipid infusion also increased extracellular signal-regulated kinase (ERK) phosphorylation (p < 0.05) and tended to reduce the content of inhibitor of kappa Bα (p = 0.09). The muscle content of most diacylglycerol, ceramide and acylcarnitine species was unaffected. In summary, insulin resistance induced by prolonged low-dose lipid infusion occurs together with increased TLR-driven inflammatory signalling and impaired insulin-stimulated IRS-1 tyrosine phosphorylation. A sustained, mild elevation in plasma NEFA is sufficient to increase TLR expression and TLR-driven signalling (NFκB and MAPK) in lean individuals. The activation of this pathway by NEFA may be involved in the pathogenesis of insulin resistance in humans. ClinicalTrials.gov NCT01740817.

Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

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Bassols Anna

2011-07-01

Full Text Available Abstract Background Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT when its association with a particular metabolic trait achieved a nominal P value Results A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues.

Broiler meat quality: Proteins and lipids of muscle tissue ...

African Journals Online (AJOL)

Proteins and lipids of muscle tissue are important meat quality parameters. They contribute substantially to the nutritional characteristics of meat. A number of studies has been conducted on the effect of different factors on the protein and lipid content of broiler meat. Given the above, the subject matter of the present paper ...

Evidence that muscle cells do not express the histidine-rich glycoprotein associated with AMP deaminase but can internalise the plasma protein

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A.R.M. Sabbatini

2011-02-01

Full Text Available Histidine-rich glycoprotein (HRG is synthesized by liver and is present at relatively high concentration in the plasma of vertebrates. We have previously described the association of a HRG-like molecule to purified rabbit skeletal muscle AMP deaminase (AMPD. We also provided the first evidence for the presence of a HRG-like protein in human skeletal muscle where a positive correlation between HRG content and total determined AMPD activity has been shown. In the present paper we investigate the origin of skeletal muscle HRG. The screening of a human skeletal muscle cDNA expression library using an anti-HRG antibody failed to reveal any positive clone. The RT-PCR analysis, performed on human skeletal muscle RNA as well as on RNA from the rhabdomyosarcoma (RD cell line, failed to show any mRNA specific for the plasma HRG or for the putative muscle variant. When the RD cells were incubated with human plasma HRG, a time-dependent increase of the HRG immunoreactivity was detected both at the plasma membrane level and intracellularly. The internalisation of HRG was inhibited by the addition of heparin. The above data strongly suggest that skeletal muscle cells do not synthesize the muscle variant of HRG but instead can actively internalise it from plasma.

Volumetric Muscle Loss: Persistent Functional Deficits Beyond Frank Loss of Tissue

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2014-09-18

and fascia covering the tibialis anterior (TA) muscle were bluntly separated from the musculature. The tissue covering all aspects of the middle...testing system.5 Peak TA muscle isometric torque was determined with the ankle at a right angle 0˚ and 20˚ of dorsi- or plantar flexion, assuming a moment...of plantar and dorsiflexion). At all joint angles, VML resulted in a significant functional deficit, although a greater torque deficit was observed

Adipose tissue extracts plasma ammonia after sprint exercise in women and men

DEFF Research Database (Denmark)

Esbjörnsson, Mona; Bülow, Jens; Norman, Barbara

2006-01-01

This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein......) with glutamate resulting in its conversion to glutamine. Adipose tissue may thus play an important physiological role in eliminating plasma NH(3) and thereby reducing the risk of NH(3) intoxication after high-intensity exercise.......This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein...... before and after three repeated 30-s cycle sprints separated by 20 min of recovery. Biopsies from subcutaneous abdominal adipose tissue were obtained and analyzed for glutamine and glutamate content. After exercise, both arterial and abdominal venous plasma NH(3) concentrations were lower in women than...

Exercise-intensity dependent alterations in plasma redox status do not reflect skeletal muscle redox-sensitive protein signaling.

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Parker, Lewan; Trewin, Adam; Levinger, Itamar; Shaw, Christopher S; Stepto, Nigel K

2018-04-01

Redox homeostasis and redox-sensitive protein signaling play a role in exercise-induced adaptation. The effects of sprint-interval exercise (SIE), high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CMIE), on post-exercise plasma redox status are unclear. Furthermore, whether post-exercise plasma redox status reflects skeletal muscle redox-sensitive protein signaling is unknown. In a randomized crossover design, eight healthy adults performed a cycling session of HIIE (5×4min at 75% W max ), SIE (4×30s Wingate's), and CMIE work-matched to HIIE (30min at 50% of W max ). Plasma hydrogen peroxide (H 2 O 2 ), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) activity, and catalase activity were measured immediately post, 1h, 2h and 3h post-exercise. Plasma redox status biomarkers were correlated with phosphorylation of skeletal muscle p38-MAPK, JNK, NF-κB, and IκBα protein content immediately and 3h post-exercise. Plasma catalase activity was greater with SIE (56.6±3.8Uml -1 ) compared to CMIE (42.7±3.2, pexercise plasma TBARS and SOD activity significantly (pexercise protocol. A significant positive correlation was detected between plasma catalase activity and skeletal muscle p38-MAPK phosphorylation 3h post-exercise (r=0.40, p=0.04). No other correlations were detected (all p>0.05). Low-volume SIE elicited greater post-exercise plasma catalase activity compared to HIIE and CMIE, and greater H 2 O 2 compared to CMIE. Plasma redox status did not, however, adequately reflect skeletal muscle redox-sensitive protein signaling. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Composition, Architecture, and Functional Implications of the Connective Tissue Network of the Extraocular Muscles

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McLoon, Linda K.; Vicente, André; Fitzpatrick, Krysta R.; Lindström, Mona

2018-01-01

Purpose We examined the pattern and extent of connective tissue distribution in the extraocular muscles (EOMs) and determined the ability of the interconnected connective tissues to disseminate force laterally. Methods Human EOMs were examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin using immunohistochemistry. Connective tissue distribution was examined with scanning electron microscopy. Rabbit EOMs were examined for levels of force transmission longitudinally and transversely using in vitro force assessment. Results Collagens I, III, and VI localized to the endomysium, perimysium, and epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina surrounding all myofibers. All collagens localized similarly in the orbital and global layers throughout the muscle length. Elastin had the most irregular pattern and ran longitudinally and circumferentially throughout the length of all EOMs. Scanning electron microscopy showed these elements to be extensively interconnected, from endomysium through the perimysium to the epimysium surrounding the whole muscle. In vitro physiology demonstrated force generation in the lateral dimension, presumably through myofascial transmission, which was always proportional to the force generated in the longitudinally oriented muscles. Conclusions A striking connective tissue matrix interconnects all the myofibers and extends, via perimysial connections, to the epimysium. These interconnections are significant and allow measurable force transmission laterally as well as longitudinally, suggesting that they may contribute to the nonlinear force summation seen in motor unit recording studies. This provides strong evidence that separate compartmental movements are unlikely as no region is independent of the rest of the muscle. PMID:29346490

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

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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

Evaluation of human muscle hardness after dynamic exercise with ultrasound real-time tissue elastography: A feasibility study

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Yanagisawa, O., E-mail: o.yanagisawa@aoni.waseda.jp [Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama (Japan); Niitsu, M. [Department of Radiological Science, Faculty of Health Sciences, Tokyo Metropolitan University, Arakawa-ku, Tokyo (Japan); Kurihara, T. [Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu, Shiga (Japan); Fukubayashi, T. [Faculty of Sport Sciences, Waseda University, Tokorozawa, Saitama (Japan)

2011-09-15

Aim: To assess the feasibility of ultrasound real-time tissue elastography (RTE) for measuring exercise-induced changes in muscle hardness and to compare the findings of RTE with those of a tissue hardness meter for semi-quantitative assessment of the hardness of exercised muscles. Materials and methods: Nine male participants performed an arm-curl exercise. RTE measurements were performed by manually applying repetitive compression with the transducer on the scan position before exercise, immediately after exercise, and at 30 min after exercise; strain ratios between muscle and a reference material (hydrogel) were calculated (muscle strain/material strain). A tissue hardness meter was also used to evaluate muscle hardness. The intraclass correlation coefficients (ICCs) for the three repeated measurements at each measurement time were calculated to evaluate the intra-observer reproducibility of each technique. Results: Immediately after exercise, the strain ratio and the value obtained using the tissue hardness meter significantly decreased (from 1.65 to 1.35) and increased (from 51.8 to 54.3), respectively. Both parameters returned to their pre-exercise value 30 min after exercise. The ICCs of the RTE (and the ICCs of the muscle hardness meter) were 0.971 (0.816) before exercise, 0.939 (0.776) immediately after exercise, and 0.959 (0.882) at 30 min after exercise. Conclusion: Similar to the muscle hardness meter, RTE revealed the exercise-induced changes of muscle hardness semi-quantitatively. The intra-observer reproducibility of RTE was very high at each measurement time. These findings suggest that RTE is a clinically useful technique for assessing hardness of specific exercised muscles.

Evaluation of human muscle hardness after dynamic exercise with ultrasound real-time tissue elastography: A feasibility study

International Nuclear Information System (INIS)

Yanagisawa, O.; Niitsu, M.; Kurihara, T.; Fukubayashi, T.

2011-01-01

Aim: To assess the feasibility of ultrasound real-time tissue elastography (RTE) for measuring exercise-induced changes in muscle hardness and to compare the findings of RTE with those of a tissue hardness meter for semi-quantitative assessment of the hardness of exercised muscles. Materials and methods: Nine male participants performed an arm-curl exercise. RTE measurements were performed by manually applying repetitive compression with the transducer on the scan position before exercise, immediately after exercise, and at 30 min after exercise; strain ratios between muscle and a reference material (hydrogel) were calculated (muscle strain/material strain). A tissue hardness meter was also used to evaluate muscle hardness. The intraclass correlation coefficients (ICCs) for the three repeated measurements at each measurement time were calculated to evaluate the intra-observer reproducibility of each technique. Results: Immediately after exercise, the strain ratio and the value obtained using the tissue hardness meter significantly decreased (from 1.65 to 1.35) and increased (from 51.8 to 54.3), respectively. Both parameters returned to their pre-exercise value 30 min after exercise. The ICCs of the RTE (and the ICCs of the muscle hardness meter) were 0.971 (0.816) before exercise, 0.939 (0.776) immediately after exercise, and 0.959 (0.882) at 30 min after exercise. Conclusion: Similar to the muscle hardness meter, RTE revealed the exercise-induced changes of muscle hardness semi-quantitatively. The intra-observer reproducibility of RTE was very high at each measurement time. These findings suggest that RTE is a clinically useful technique for assessing hardness of specific exercised muscles.

Enhanced contractile force generation by artificial skeletal muscle tissues using IGF-I gene-engineered myoblast cells.

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Sato, Masanori; Ito, Akira; Kawabe, Yoshinori; Nagamori, Eiji; Kamihira, Masamichi

2011-09-01

The aim of this study was to investigate whether insulin-like growth factor (IGF)-I gene delivery to myoblast cells promotes the contractile force generated by hydrogel-based tissue-engineered skeletal muscles in vitro. Two retroviral vectors allowing doxycycline (Dox)-inducible expression of the IGF-I gene were transduced into mouse myoblast C2C12 cells to evaluate the effects of IGF-I gene expression on these cells. IGF-I gene expression stimulated the proliferation of C2C12 cells, and a significant increase in the growth rate was observed for IGF-I-transduced C2C12 cells with Dox addition, designated C2C12/IGF (Dox+) cells. Quantitative morphometric analyses showed that the myotubes induced from C2C12/IGF (Dox+) cells had a larger area and a greater width than control myotubes induced from normal C2C12 cells. Artificial skeletal muscle tissues were prepared from the respective cells using hydrogels composed of type I collagen and Matrigel. Western blot analyses revealed that the C2C12/IGF (Dox+) tissue constructs showed activation of a skeletal muscle hypertrophy marker (Akt) and enhanced expression of muscle-specific markers (myogenin, myosin heavy chain and tropomyosin). Moreover, the creatine kinase activity was increased in the C2C12/IGF (Dox+) tissue constructs. The C2C12/IGF (Dox+) tissue constructs contracted in response to electrical pulses, and generated a significantly higher physical force than the control C2C12 tissue constructs. These findings indicate that IGF-I gene transfer has the potential to yield functional skeletal muscle substitutes that are capable of in vivo restoration of the load-bearing function of injured muscle or acting as in vitro electrically-controlled bio-actuators. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Changes in muscle tissue oxygenation during stagnant ischemia in septic patients.

Science.gov (United States)

Pareznik, Roman; Knezevic, Rajko; Voga, Gorazd; Podbregar, Matej

2006-01-01

To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock. Prospective observational study in the medical ICU of a general hospital. Consecutive patients admitted to ICU with septic shock (n=6), severe sepsis (n=6), localized infection (n=3), and healthy volunteers (n=15). Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm. Thenar muscle tissue oxygen saturation (StO2) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia. StO(2) before intervention was comparable in patients with septic shock, severe sepsis, or localized infection and healthy volunteers (89 [65, 92]% vs. 82 [72, 91]% vs. 87 [85, 92]% vs. 83 [79, 93]%, respectively; p>0.1). The rate of StO(2) decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls (-7.0 [-3.6, -11.0] %/min vs. -10.4 [-7.8, -13.3] %/min vs. -19.5 [-12.3, -23.3] vs. -37.4 [-27.3, -56.2] %/min, respectively; p=0.041). At ICU discharge the rate of StO2 decrease did not differ between the septic shock, severe sepsis, and localized infection groups (-17.0 [-9.3, -28.9] %/min vs. -19.9 [-13.3, -23.6] %/min vs. -23.1 [-20.7, -26.2] %/min, respectively), but remained slower than in controls (p<0.01). The rate of StO2 decrease was correlated with Sequential Organ Failure Assessment (SOFA) score (r=0.739, p<0.001). After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers. During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score.

Insulin action in adipose tissue and muscle in hypothyroidism.

Science.gov (United States)

Dimitriadis, George; Mitrou, Panayota; Lambadiari, Vaia; Boutati, Eleni; Maratou, Eirini; Panagiotakos, Demosthenes B; Koukkou, Efi; Tzanela, Marinela; Thalassinos, Nikos; Raptis, Sotirios A

2006-12-01

Although insulin resistance in thyroid hormone excess is well documented, information on insulin action in hypothyroidism is limited. To investigate this, a meal was given to 11 hypothyroid (HO; aged 45 +/- 3 yr) and 10 euthyroid subjects (EU; aged 42 +/- 4 yr). Blood was withdrawn for 360 min from veins (V) draining the anterior abdominal sc adipose tissue and the forearm and from the radial artery (A). Blood flow (BF) in adipose tissue was measured with 133Xe and in forearm with strain-gauge plethysmography. Tissue glucose uptake was calculated as (A-V)glucose(BF), lipoprotein lipase as (A-V)Triglycerides(BF), and lipolysis as [(V-A)glycerol(BF)]-lipoprotein lipase. The HO group had higher glucose and insulin levels than the EU group (P hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue.

[Mg2+, ATP-dependent plasma membrane calcium pump of smooth muscle cells. I. Structural organization and properties].

Science.gov (United States)

Veklich, T O; Mazur, Iu Iu; Kosterin, S O

2015-01-01

Tight control of cytoplasm Ca2+ concentration is essential in cell functioning. Changing of Ca2+ concentration is thorough in smooth muscle cells, because it determines relaxation/constraint process. One of key proteins which control Ca2+ concentration in cytoplasm is Mg2+, ATP-dependent plasma membrane calcium pump. Thus, it is important to find compoumds which allowed one to change Mg2+, ATP-dependent plasma membrane calcium pump activity, as long as this topic is of current interest in biochemical research which regards energy and pharmacomechanical coupling mechanism of muscle excitation and contraction. In this article we generalized literatute and own data about properties of smooth muscle cell plasma membrane Ca(2+)-pump. Stuctural oganization, kinetical properties and molecular biology are considered.

Effect of vanadate on glucose transporter (GLUT4) intrinsic activity in skeletal muscle plasma membrane giant vesicles

DEFF Research Database (Denmark)

Kristiansen, S; Youn, J; Richter, Erik

1996-01-01

of vanadate (NaVO3) on glucose transporter (GLUT4) intrinsic activity (V(max) = intrinsic activity x [GLUT4 protein]) was studied in muscle plasma membrane giant vesicles. Giant vesicles (average diameter 7.6 microns) were produced by collagenase treatment of rat skeletal muscle. The vesicles were incubated......) 55% and 60%, respectively, compared with control. The plasma membrane GLUT4 protein content was not changed in response to vanadate. It is concluded that vanadate decreased glucose transport per GLUT4 (intrinsic activity). This finding suggests that regulation of glucose transport in skeletal muscle...

Effect of hypertensive rat plasma on ion transport of cultured vascular smooth muscle

International Nuclear Information System (INIS)

Magargal, W.W.; Overbeck, H.W.

1986-01-01

We layered fresh, unprocessed plasma from healthy rats with early (less than or equal to 7 days) or benign, chronic (greater than 3 wk) one-kidney, one-clip hypertension and from paired one-kidney normotensive control rats over confluent primary-cultured rat aortic smooth muscle cells. Plasma from all rats increased cellular ouabain-sensitive 86 Rb + uptake and sodium content and decreased ouabain-insensitive 86 Rb + uptake compared with uptakes and content in the presence of balanced salt solution (P less than 0.01). Cells incubated in the presence of plasma from rats with early (P less than 0.02) or chronic hypertension (P less than 0.01) had significantly reduced ouabain-sensitive 86 Rb + uptake when compared with cells incubated in normotensive plasma, but their intracellular Na+ contents were not lower. We no longer detected this uptake difference when chronic hypertensives drank 0.9% NaCl instead of water. Plasma from hypertensive rats also altered ouabain-insensitive 86 Rb + uptake by the cultured cells. These findings of this new, reproducible, and specific assay system support the hypothesis that plasma factors inhibit the membrane sodium-potassium pump in vascular smooth muscle cells in this form of hypertension. The abnormality occurs in both early and chronic stages, but may not be related to sodium intake. The data also provide evidence for plasma factors in hypertension altering membrane K+ permeability

A DIC Based Technique to Measure the Contraction of a Skeletal Muscle Engineered Tissue

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Emanuele Rizzuto

2016-01-01

Full Text Available Tissue engineering is a multidisciplinary science based on the application of engineering approaches to biologic tissue formation. Engineered tissue internal organization represents a key aspect to increase biofunctionality before transplant and, as regarding skeletal muscles, the potential of generating contractile forces is dependent on the internal fiber organization and is reflected by some macroscopic parameters, such as the spontaneous contraction. Here we propose the application of digital image correlation (DIC as an independent tool for an accurate and noninvasive measurement of engineered muscle tissue spontaneous contraction. To validate the proposed technique we referred to the X-MET, a promising 3-dimensional model of skeletal muscle. The images acquired through a high speed camera were correlated with a custom-made algorithm and the longitudinal strain predictions were employed for measuring the spontaneous contraction. The spontaneous contraction reference values were obtained by studying the force response. The relative error between the spontaneous contraction frequencies computed in both ways was always lower than 0.15%. In conclusion, the use of a DIC based system allows for an accurate and noninvasive measurement of biological tissues’ spontaneous contraction, in addition to the measurement of tissue strain field on any desired region of interest during electrical stimulation.

Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

International Nuclear Information System (INIS)

Canuto, K S; Sergio, L P S; Mencalha, A L; Fonseca, A S; Paoli, F

2016-01-01

Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases. (paper)

Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

DEFF Research Database (Denmark)

Langberg, H; Bjørn, C; Boushel, Robert Christopher

2002-01-01

been established. Microdialysis (molecular mass cut-off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years...... increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P increases the interstitial concentrations......Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet...

Evaluation of several techniques to modify denatured muscle tissue to obtain a scaffold for peripheral nerve regeneration

NARCIS (Netherlands)

Meek, MF; den Dunnen, WFA; Schakenraad, JM; Robinson, PH

The aim of this study was to (1) evaluate the effect of several preparation techniques of denatured muscle tissue to obtain an open three-dimensional structure, and (2) test if this scaffold is suitable for peripheral nerve regeneration. Four samples (A-D) of muscle tissue specimens were evaluated

A pilot study using Tissue Velocity Ultrasound Imaging (TVI to assess muscle activity pattern in patients with chronic trapezius myalgia

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Brodin Lars-Åke

2008-09-01

Full Text Available Abstract Background Different research techniques indicate alterations in muscle tissue and in neuromuscular control of aching muscles in patients with chronic localized pain. Ultrasound can be used for analysis of muscle tissue dynamics in clinical practice. Aim This study introduces a new muscle tissue sensitive ultrasound technique in order to provide a new methodology for providing a description of local muscle changes. This method is applied to investigate trapezius muscle tissue response – especially with respect to specific regional deformation and deformation rates – during concentric shoulder elevation in patients with chronic trapezius myalgia and healthy controls before and after pain provocation. Methods Patients with trapezius myalgia and healthy controls were analyzed using an ultrasound system equipped with tissue velocity imaging (TVI. The patients performed a standardized 3-cm concentric shoulder elevation before and after pain provocation/exercise at a standardized elevation tempo (30 bpm. A standardized region of interest (ROI, an ellipsis with a size that captures the upper and lower fascia of the trapezius muscle (4 cm width at rest, was placed in the first frame of the loop registration of the elevation. The ROI was re-anchored frame by frame following the same anatomical landmark in the basal fascia during all frames of the concentric phase. In cardiac measurement, tissue velocities are measured in the axial projection towards and against the probe where red colour represents shortening and red lengthening. In the case of measuring the trapezius muscle, tissue deformation measurements are made orthogonally, thus, indirectly. Based on the assumption of muscle volume incompressibility, blue represents tissue contraction and red relaxation. Within the ROI, two variables were calculated as a function of time: deformation and deformation rate. Hereafter, max, mean, and quadratic mean values (RMS of each variable were

Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

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Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

1998-01-01

Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

Chitosan-based scaffolds for the support of smooth muscle constructs in intestinal tissue engineering

Science.gov (United States)

Zakhem, Elie; Raghavan, Shreya; Gilmont, Robert R; Bitar, Khalil N

2012-01-01

Intestinal tissue engineering is an emerging field due to a growing demand for intestinal lengthening and replacement procedures secondary to massive resections of the bowel. Here, we demonstrate the potential use of a chitosan/collagen scaffold as a 3D matrix to support the bioengineered circular muscle constructs maintain their physiological functionality. We investigated the biocompatibility of chitosan by growing rabbit colonic circular smooth muscle cells (RCSMCs) on chitosan-coated plates. The cells maintained their spindle-like morphology and preserved their smooth muscle phenotypic markers. We manufactured tubular scaffolds with central openings composed of chitosan and collagen in a 1:1 ratio. Concentrically-aligned 3D circular muscle constructs were bioengineered using fibrin-based hydrogel seeded with RCSMCs. The constructs were placed around the scaffold for 2 weeks, after which they were taken off and tested for their physiological functionality. The muscle constructs contracted in response to Acetylcholine (Ach) and potassium chloride (KCl) and they relaxed in response to vasoactive intestinal peptide (VIP). These results demonstrate that chitosan is a biomaterial possibly suitable for intestinal tissue engineering applications. PMID:22483012

Quantitative ultrasound tissue characterization in shoulder and thigh muscles – a new approach

DEFF Research Database (Denmark)

Nielsen, P.K.; Jensen, B.R.; Darvann, Tron Andre

2006-01-01

Background: The echogenicity patterns of ultrasound scans contain information of tissue composition in muscles. The aim was: ( 1) to develop a quantitative ultrasound image analysis to characterize tissue composition in terms of intensity and structure of the ultrasound images, and ( 2) to use th...

Repeated Muscle Injury as a Presumptive Trigger for Chronic Masticatory Muscle Pain

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Dean Dessem

2011-01-01

Full Text Available skeletal muscles sustain a significant loss of maximal contractile force after injury, but terminally damaged fibers can eventually be replaced by the growth of new muscle (regeneration, with full restoration of contractile force over time. After a second injury, limb muscles exhibit a smaller reduction in maximal force and reduced inflammation compared with that after the initial injury (i.e., repeated bout effect. In contrast, masticatory muscles exhibit diminished regeneration and persistent fibrosis, after a single injury; following a second injury, plasma extravasation is greater than after a single injury and maximal force is decreased more than after the initial injury. Thus, masticatory muscles do not exhibit a repeated bout effect and are instead increasingly damaged by repeated injury. We propose that the impaired ability of masticatory muscles to regenerate contributes to chronic muscle pain by leading to an accumulation of tissue damage, fibrosis, and a persistent elevation and prolonged membrane translocation of nociceptive channels such as P2X3 as well as enhanced expression of neuropeptides including CGRP within primary afferent neurons. These transformations prime primary afferent neurons for enhanced responsiveness upon subsequent injury thus triggering and/or exacerbating chronic muscle pain.

Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies.

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Kryštůfková, Olga; Barbasso Helmers, Sevim; Venalis, Paulius; Malmström, Vivianne; Lindroos, Eva; Vencovský, Jiří; Lundberg, Ingrid E

2014-10-10

Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers. Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNα/β-inducible myxovirus resistance-1 protein (MX-1). BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08). The expression

Maternal nutrient restriction in early gestation upregulates myogenic genes in cattle fetal muscle tissue

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Prenatal myogenesis is a critical factor in determining the muscle growth potential of cattle. We hypothesized that maternal nutrient restriction during early gestation would alter the transcriptome of fetal primordial muscle tissue in cattle. A total of 14 Angus-cross heifers were estrus synchroniz...

Effects of branched-chain amino acids supplementation on both plasma amino acids concentration and muscle energetics changes resulting from muscle damage: A randomized placebo controlled trial.

Science.gov (United States)

Fouré, Alexandre; Nosaka, Kazunori; Gastaldi, Marguerite; Mattei, Jean-Pierre; Boudinet, Hélène; Guye, Maxime; Vilmen, Christophe; Le Fur, Yann; Bendahan, David; Gondin, Julien

2016-02-01

Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal Mitochondria in Lean but Not Obese Humans.

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Kras, Katon A; Hoffman, Nyssa; Roust, Lori R; Patel, Shivam H; Carroll, Chad C; Katsanos, Christos S

2017-12-01

Obesity is associated with mitochondrial dysfunction in skeletal muscle. Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial adenosine triphosphate (ATP) production in lean individuals. To determine whether acute elevation in plasma AAs enhances muscle mitochondrial respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in obese adults. Assessment of SS and IMF mitochondrial function during saline (i.e., control) and AA infusions. Eligible participants were healthy lean (body mass index, mass index >30 kg/m2; age 35 ± 3 years; n = 11) subjects. Single trial of saline infusion followed by AA infusion. SS and IMF mitochondria were isolated from muscle biopsies collected at the end of the saline and AA infusions. Mitochondrial respiration and ATP production. AA infusion increased adenosine 5'-diphosphate (ADP)-stimulated respiration and ATP production rates of SS mitochondria in the lean (P lean subjects only (P lean or obese subjects (P > 0.05). Increasing the plasma AA concentrations enhances the capacity for respiration and ATP production of muscle SS, but not IMF, mitochondria in lean individuals, in parallel with increases in uncoupled respiration. However, neither of these parameters increases in muscle SS or IMF mitochondria in obese individuals. Copyright © 2017 Endocrine Society

Engineering Cardiac Muscle Tissue: A Maturating Field of Research.

Science.gov (United States)

Weinberger, Florian; Mannhardt, Ingra; Eschenhagen, Thomas

2017-04-28

Twenty years after the initial description of a tissue engineered construct, 3-dimensional human cardiac tissues of different kinds are now generated routinely in many laboratories. Advances in stem cell biology and engineering allow for the generation of constructs that come close to recapitulating the complex structure of heart muscle and might, therefore, be amenable to industrial (eg, drug screening) and clinical (eg, cardiac repair) applications. Whether the more physiological structure of 3-dimensional constructs provides a relevant advantage over standard 2-dimensional cell culture has yet to be shown in head-to-head-comparisons. The present article gives an overview on current strategies of cardiac tissue engineering with a focus on different hydrogel methods and discusses perspectives and challenges for necessary steps toward the real-life application of cardiac tissue engineering for disease modeling, drug development, and cardiac repair. © 2017 American Heart Association, Inc.

Increased plasma lipid levels exacerbate muscle pathology in the mdx mouse model of Duchenne muscular dystrophy.

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Milad, Nadia; White, Zoe; Tehrani, Arash Y; Sellers, Stephanie; Rossi, Fabio M V; Bernatchez, Pascal

2017-09-12

Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin expression and leads to severe ambulatory and cardiac function decline. However, the dystrophin-deficient mdx murine model of DMD only develops a very mild form of the disease. Our group and others have shown vascular abnormalities in animal models of MD, a likely consequence of the fact that blood vessels express the same dystrophin-associated glycoprotein complex (DGC) proteins as skeletal muscles. To test the blood vessel contribution to muscle damage in DMD, mdx 4cv mice were given elevated lipid levels via apolipoprotein E (ApoE) gene knockout combined with normal chow or lipid-rich Western diets. Ambulatory function and heart function (via echocardiogram) were assessed at 4 and 7 months of age. After sacrifice, muscle histology and aortic staining were used to assess muscle pathology and atherosclerosis development, respectively. Plasma levels of total cholesterol, high-density lipoprotein (HDL), triglycerides, and creatine kinase (CK) were also measured. Although there was an increase in left ventricular heart volume in mdx-ApoE mice compared to that in mdx mice, parameters of heart function were not affected. Compared with wild-type and ApoE-null, only mdx-ApoE KO mice showed significant ambulatory dysfunction. Despite no significant difference in plasma CK, histological analyses revealed that elevated plasma lipids in chow- and Western diet-fed mdx-ApoE mice was associated with severe exacerbation of muscle pathology compared to mdx mice: significant increase in myofiber damage and fibrofatty replacement in the gastrocnemius and triceps brachii muscles, more reminiscent of human DMD pathology. Finally, although both ApoE and mdx-ApoE groups displayed increased plasma lipids, mdx-ApoE exhibited atherosclerotic plaque deposition equal to or less than that of ApoE mice. Since others have shown that lipid abnormalities correlate with DMD severity, our data suggest that plasma lipids could be

Unaccustomed eccentric contractions impair plasma K+ regulation in the absence of changes in muscle Na+,K+-ATPase content.

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Craig A Goodman

Full Text Available The Na+,K+-ATPase (NKA plays a fundamental role in the regulation of skeletal muscle membrane Na+ and K+ gradients, excitability and fatigue during repeated intense contractions. Many studies have investigated the effects of acute concentric exercise on K+ regulation and skeletal muscle NKA, but almost nothing is known about the effects of repeated eccentric contractions. We therefore investigated the effects of unaccustomed maximal eccentric knee extensor contractions on K+ regulation during exercise, peak knee extensor muscle torque, and vastus lateralis muscle NKA content and 3-O-MFPase activity. Torque measurements, muscle biopsies, and venous blood samples were taken before, during and up to 7 days following the contractions in six healthy adults. Eccentric contractions reduced peak isometric muscle torque immediately post-exercise by 26±11% and serum creatine kinase concentration peaked 24 h post-exercise at 339±90 IU/L. During eccentric contractions, plasma [K+] rose during Set 1 and remained elevated at ∼4.9 mM during sets 4-10; this was despite a decline in work output by Set 4, which fell by 18.9% at set 10. The rise in plasma [K+] x work(-1 ratio was elevated over Set 2 from Set 4- Set 10. Eccentric contractions had no effect on muscle NKA content or maximal in-vitro 3-O-MFPase activity immediately post- or up to 7 d post-exercise. The sustained elevation in plasma [K+] despite a decrease in work performed by the knee extensor muscles suggests an impairment in K+ regulation during maximal eccentric contractions, possibly due to increased plasma membrane permeability or to excitation-contraction uncoupling.

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

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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.

Metabolism of 15(p123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues

International Nuclear Information System (INIS)

Reske, S.N.; Sauer, W.; Winkler, C.; Machulla, H.J.; Knust, J.

1985-01-01

The uptake and turnover of W(p 123 I iodophenyl-)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in the heart, lung, liver, kidneys, spleen, and skeletal muscle of rats. At 2 min post injection, a high cardiac uptake of 4.4% dose per gram had already been achieved; this was followed by a rapid, two-component, tracer clearance. The kinetics of tissue concentrations of labeled hydrophilic catabolites indicated a rapid oxidation of I-PPA and the subsequent washout of I-PPA catabolites from heart-muscle tissue. The fractional distribution of the labeled cardiac lipids compared favorably with previously reported values for 3 H-oleic- or 14 C-palmitic-acid-labeled myocardial lipids. Typical patterns of I-PPA metabolism were observed in tissues; dedpending on primary fatty-acid oxidation, lipid metabolism regulation, or I-PPA-catabolite excretion. The tissue concentrations and kinetics of I-PPA and its metabolites in the heart muscle indicated that general pathways of cardiac-lipid metabolism are traced by this new γ-emitting isotope-labeled radiopharmaceutical. (orig.)

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria.

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Julie Bachmann

2014-04-01

Full Text Available Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

YKL-40 tissue expression and plasma levels in patients with ovarian cancer

DEFF Research Database (Denmark)

Høgdall, Estrid V S; Ringsholt, Merete; Høgdall, Claus K

2009-01-01

survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. METHODS: YKL-40 protein expression was determined by immunohistochemistry...... in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. RESULTS: YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor...... stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40-3.25, p = 0.0004). CONCLUSION: YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic...

Use of plasma creatine kinase pharmacokinetics to estimate the amount of excercise-induced muscle damage in Beagles.

Science.gov (United States)

Chanoit, G P; Lefebvre, H P; Orcel, K; Laroute, V; Toutain, P L; Braun, J P

2001-09-01

To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs. 6 untrained adult Beagles. The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (CI) were used to estimate muscle damage. At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32+/-0.02 ml/kg of body weight/min, 57+/-173 ml/kg, and 3.0+/-0.57 h, respectively. During exercise, Cl decreased significantly (0.26+/-0.03 ml/kg/min), MRT increased significantly, (4.4+/-0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151+/-58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41+/-29.3 mg/kg. These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage.

Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

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Rønning, Sissel B; Carlson, Cathrine R; Stang, Espen; Kolset, Svein O; Hollung, Kristin; Pedersen, Mona E

2015-01-01

The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

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Sissel B Rønning

Full Text Available The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering.

Science.gov (United States)

Maffioletti, Sara Martina; Sarcar, Shilpita; Henderson, Alexander B H; Mannhardt, Ingra; Pinton, Luca; Moyle, Louise Anne; Steele-Stallard, Heather; Cappellari, Ornella; Wells, Kim E; Ferrari, Giulia; Mitchell, Jamie S; Tyzack, Giulia E; Kotiadis, Vassilios N; Khedr, Moustafa; Ragazzi, Martina; Wang, Weixin; Duchen, Michael R; Patani, Rickie; Zammit, Peter S; Wells, Dominic J; Eschenhagen, Thomas; Tedesco, Francesco Saverio

2018-04-17

Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Measurements of the static friction coefficient between bone and muscle tissues.

Science.gov (United States)

Shacham, Sharon; Castel, David; Gefen, Amit

2010-08-01

This study aimed at measuring the static coefficient of friction (mu) between bone and skeletal muscle tissues in order to support finite element (FE) modeling in orthopaedic and rehabilitation research, where such contact conditions need to be defined. A custom-made friction meter (FM) that employs the load cell and motion-controlled loading arm of a materials testing machine was designed for this study. The FM was used to measure mu between fresh ulna bones and extensor muscles surrounding the ulna, which were harvested from five young adult pigs. Mean bone-muscle mu were between 0.36 and 0.29, decreased with the increase in loads applied on the bone (p<0.05) and plateaued at a mean approximately 0.3 for loads exceeding 4 N. Hence, for FE modeling of bone-muscle contacts through which loads with magnitudes of kgs to 10s-of-kgs are transferred, assuming mu of approximately 0.3 appears to be appropriate.

Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle.

Science.gov (United States)

Nugent, William H; Song, Bjorn K; Pittman, Roland N; Golub, Aleksander S

2016-05-01

Under physiologic conditions, microvascular oxygen delivery appears to be well matched to oxygen consumption in respiring tissues. We present a technique to measure interstitial oxygen tension (PISFO2) and oxygen consumption (VO2) under steady-state conditions, as well as during the transitions from rest to activity and back. Phosphorescence Quenching Microscopy (PQM) was employed with pneumatic compression cycling to achieve 1 to 10 Hz sampling rates of interstitial PO2 and simultaneous recurrent sampling of VO2 (3/min) in the exteriorized rat spinotrapezius muscle. The compression pressure was optimized to 120-130 mmHg without adverse effect on the tissue preparation. A cycle of 5s compression followed by 15s recovery yielded a resting VO2 of 0.98 ± 0.03 ml O2/100 cm(3)min while preserving microvascular oxygen delivery. The measurement system was then used to assess VO2 dependence on PISFO2 at rest and further tested under conditions of isometric muscle contraction to demonstrate a robust ability to monitor the on-kinetics of tissue respiration and the compensatory changes in PISFO2 during contraction and recovery. The temporal and spatial resolution of this approach is well suited to studies seeking to characterize microvascular oxygen supply and demand in thin tissues. Copyright © 2015 Elsevier Inc. All rights reserved.

Model of electrical conductivity of skeletal muscle based on tissue structure

NARCIS (Netherlands)

Gielen, F.L.H.; Cruts, H.E.P.; Alberts, B.A.; Boon, K.L.; Wallinga, W.; Boom, H.B.K.

1986-01-01

Recent experiments carried out in our laboratory with the four-electrode method showed that the electrical conductivity of skeletal muscle tissue depends on the frequency of the injected current and the distance between the current electrodes. A model is proposed in order to study these effects. The

Lipid accumulation, oxidative stress and immune-related molecules affected by tributyltin exposure in muscle tissues of rare minnow (Gobiocypris rarus).

Science.gov (United States)

Zhang, Jiliang; Zhang, Chunnuan; Ma, Dongdong; Liu, Min; Huang, Shuntao

2017-12-01

Tributyltin (TBT) is reported to induce adipogenesis in fish, which might affect nutritional qualities and health status. Muscle tissues account for the majority of body mass, and have been described as a major site of fat deposition and an immunologically active organ. Therefore, the present study aims to evaluate whether chronic exposures of TBT, at environmental concentrations of 1, 10 and 100 ng/L, affects lipid accumulation, oxidative stress and immune status in muscle tissues of rare minnow (Gobiocypris rarus). After 60 d of exposure, TBT increased contents of total lipid, total cholesterol, triglyceride and fatty acids in muscle tissues. Interestingly, TBT exposure disrupted fatty acid composition and increased contents of unsaturated fatty acids (such as eicosapentaenoic acid and docosahexaenoic acid) in muscle tissues, which might be a response to preserve membrane functions from TBT exposure. Meanwhile, the concentrations of hepatic fatty acid desaturase 2 (Δ6-desaturase) and stearoyl-CoA desaturase (Δ9-desaturase) were increased after TBT exposure, which might contribute the increase of unsaturated fatty acids. Furthermore, TBT increased muscle lipid peroxidation products, antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), and the expression of immune-related molecules (tumor necrosis factor alpha, interleukin 1 beta and nuclear factor kappa B) in muscle tissues. The disruption of TBT on the lipid accumulation, oxidative stress and immune-toxic effects in muscle tissues of fish might reduce nutritional qualities, and affect growth and health status, which might pose a constant and serious threat to fish and result in economic loss in aquaculture. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comparative study of tissue inhibitor of metalloproteinases-1 levels in plasma and tumour tissue from patients with primary breast cancer and in plasma from patients with metastatic breast cancer

DEFF Research Database (Denmark)

Rasmussen, Anne-Sofie Schrohl; Mueller, Volkmar; Christensen, Ib Jarle

2008-01-01

OBJECTIVE: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been investigated as a potential tumour marker in breast cancer. Here we investigated the correlation between TIMP-1 in tumour tissue and plasma to evaluate whether TIMP-1 in plasma is actually a surrogate marker for TIMP-1 in prima...

Blood flow and oxygenation in peritendinous tissue and calf muscle during dynamic exercise in humans

DEFF Research Database (Denmark)

Boushel, Robert Christopher; Langberg, H; Green, Sara Marie Ehrenreich

2000-01-01

1. Circulation around tendons may act as a shunt for muscle during exercise. The perfusion and oxygenation of Achilles' peritendinous tissue was measured in parallel with that of calf muscle during exercise to determine (1) whether blood flow is restricted in peritendinous tissue during exercise......, and (2) whether blood flow is coupled to oxidative metabolism. 2. Seven individuals performed dynamic plantar flexion from 1 to 9 W. Radial artery and popliteal venous blood were sampled for O2, peritendinous blood flow was determined by 133Xe-washout, calf blood flow by plethysmography, cardiac output...

Evaluation of the role of the cyclooxygenase signaling pathway during inflammation in skin and muscle tissues of ball pythons (Python regius).

Science.gov (United States)

Sadler, Ryan A; Schumacher, Juergen P; Rathore, Kusum; Newkirk, Kim M; Cole, Grayson; Seibert, Rachel; Cekanova, Maria

2016-05-01

OBJECTIVE To determine degrees of production of cyclooxygenase (COX)-1 and -2 and other mediators of inflammation in noninflamed and inflamed skin and muscle tissues in ball pythons (Python regius). ANIMALS 6 healthy adult male ball pythons. PROCEDURES Biopsy specimens of noninflamed skin and muscle tissue were collected from anesthetized snakes on day 0. A 2-cm skin and muscle incision was then made 5 cm distal to the biopsy sites with a CO2 laser to induce inflammation. On day 7, biopsy specimens of skin and muscle tissues were collected from the incision sites. Inflamed and noninflamed tissue specimens were evaluated for production of COX-1, COX-2, phosphorylated protein kinase B (AKT), total AKT, nuclear factor κ-light-chain-enhancer of activated B cells, phosphorylated extracellular receptor kinases (ERKs) 1 and 2, and total ERK proteins by western blot analysis. Histologic evaluation was performed on H&E-stained tissue sections. RESULTS All biopsy specimens of inflamed skin and muscle tissues had higher histologic inflammation scores than did specimens of noninflamed tissue. Inflamed skin specimens had significantly greater production of COX-1 and phosphorylated ERK than did noninflamed skin specimens. Inflamed muscle specimens had significantly greater production of phosphorylated ERK and phosphorylated AKT, significantly lower production of COX-1, and no difference in production of COX-2, compared with production in noninflamed muscle specimens. CONCLUSIONS AND CLINICAL RELEVANCE Production of COX-1, but not COX-2, was significantly greater in inflamed versus noninflamed skin specimens from ball pythons. Additional research into the reptilian COX signaling pathway is warranted.

Determination of Magnesium in Needle Biopsy Samples of Muscle Tissue by Means of Neutron Activation Analysis

Energy Technology Data Exchange (ETDEWEB)

Brune, D; Sjoeberg, H E

1964-07-15

Magnesium has been determined by means of neutron-activation analysis in needle biopsy samples of the order of magnitude 1 mg dry weight. The procedure applied was to extract the Mg-27 activity from irradiated muscle tissue with concentrated hydrochloric acid followed by a fast hydroxide precipitation and gamma-spectrometric measurements. The Mg activity was recovered in the muscle tissue samples to (97 {+-} 2) per cent. The sensitivity for the magnesium determination is estimated as 0.3 {mu}g.

Influence of Bone and Muscle Injuries on the Osteogenic Potential of Muscle Progenitors: Contribution of Tissue Environment to Heterotopic Ossification.

Science.gov (United States)

Molligan, Jeremy; Mitchell, Reed; Schon, Lew; Achilefu, Samuel; Zahoor, Talal; Cho, Young; Loube, Jeffery; Zhang, Zijun

2016-06-01

: By using surgical mouse models, this study investigated how the tissue environment influences the osteogenic potential of muscle progenitors (m-progenitors) and potentially contributes to heterotopic ossification (HO). Injury was induced by clamping the gluteus maximus and medius (group M) or osteotomy of greater trochanter (group O) on the right hip, as well as combined muscle injury and osteotomy of greater trochanter (group M+O). The gluteus maximus and medius of the operated hips were harvested at days 1, 3, 5, and 10 for isolation of m-progenitors. The cells were cultured in an osteogenic medium for 3 weeks, and osteogenesis was evaluated by matrix mineralization and the expression of osteogenesis-related genes. The expression of type I collagen, RUNX2 (runt-related transcription factor 2), and osteocalcin by the m-progenitors of group M+O was significantly increased, compared with groups M and O. Osteogenic m-progenitors in group O increased the expression of bone morphogenetic protein 2 and also bone morphogenetic protein antagonist differential screening-selected gene aberrative in neuroblastoma. On histology, there was calcium deposition mostly in the muscles of group M+O harvested at day 10. CD56, representing myogenic progenitors, was highly expressed in the m-progenitors isolated from group M (day 10), but m-progenitors of group M+O (day 10) exhibited the highest expression of platelet-derived growth factor receptor α (PDGFR-α), a marker of muscle-derived mesenchymal stem cells (M-MSCs). The expressions of PDGFR-α and RUNX2 were colocalized in osteogenic m-progenitors. The data indicate that the tissue environment simulated in the M+O model is a favorable condition for HO formation. Most likely, M-MSCs, rather than myogenic progenitors, in the m-progenitors participate in HO formation. The prevalence of traumatic heterotopic ossification (HO) is high in war injury. The pathogenesis of HO is still unknown. This study clarified the contribution of a

Exercise increases the plasma membrane content of the Na+ -K+ pump and its mRNA in rat skeletal muscles.

Science.gov (United States)

Tsakiridis, T; Wong, P P; Liu, Z; Rodgers, C D; Vranic, M; Klip, A

1996-02-01

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2

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

Differences in in vivo muscle fascicle and tendinous tissue behavior between the ankle plantarflexors during running.

Science.gov (United States)

Lai, A K M; Lichtwark, G A; Schache, A G; Pandy, M G

2018-03-30

The primary human ankle plantarflexors, soleus (SO), medial gastrocnemius (MG), and lateral gastrocnemius (LG) are typically regarded as synergists and play a critical role in running. However, due to differences in muscle-tendon architecture and joint articulation, the muscle fascicles and tendinous tissue of the plantarflexors may exhibit differences in their behavior and interactions during running. We combined in vivo dynamic ultrasound measurements with inverse dynamics analyses to identify and explain differences in muscle fascicle, muscle-tendon unit, and tendinous tissue behavior of the primary ankle plantarflexors across a range of steady-state running speeds. Consistent with their role as a force generator, the muscle fascicles of the uniarticular SO shortened less rapidly than the fascicles of the MG during early stance. Furthermore, the MG and LG exhibited delays in tendon recoil during the stance phase, reflecting their ability to transfer power and work between the knee and ankle via tendon stretch and storage of elastic strain energy. Our findings add to the growing body of evidence surrounding the distinct mechanistic functions of uni- and biarticular muscles during dynamic movements. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

State of Skeletal Muscle Tissue in Women in the Ukrainian Population

Directory of Open Access Journals (Sweden)

V.V. Povoroznyuk

2015-10-01

Full Text Available Today among geriatric syndromes, world scientists pay much attention to the study of sarcopenia. It was found that the evaluation of skeletal muscle strength has a significant correlation with the risk of falls, disability, deterioration in the quality of life, duration of hospitalization. It is proved that measurements of skeletal muscle strength, but not the determination of skeletal muscles mass, are strong and independent predictors of mortality in the elderly. Further researches are needed to study the characteristics of weight loss, strength and function of skeletal muscle with age in individuals of different sex and age. The objective of this study was to explore the features of strength and functionality of skeletal muscle tissue in women of all ages. The study involved 248 women, who were divided into groups by decades depending on age: 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, 80–89 years. Skeletal muscle strength was evaluated using spring carpal dynamometer. Functions of skeletal muscles and the risk of falls were assessed using special tests. Fat-free mass of the whole body, upper and lower extremities was evaluated by means of dual-energy X-ray absorptiometry (Prodigy, GEHC Lunar, Madison, WI, USA. The study found that maximal values of strength and functional capacity of skeletal muscles were observed in women in the age group of 20–29 years. The significant loss of skeletal muscle strength is being detected in individuals from the age group of 60–69 years and older. When determining the functional capacity of skeletal muscles and risk of falls, significantly worse performance was established in women older than 50 years compared to those in women in the age group of 20–29 years.

Hepatic and muscle clearance of physostigmine in the rat after i.v. administration

International Nuclear Information System (INIS)

Somani, S.M.; Unni, L.K.

1986-01-01

This study presents a method to calculate the extraction ratio (ER) from in vivo time course of liver metabolism using the physiological and pharmacokinetic parameters such as plasma flow rate, partition coefficient of drug between tissue and plasma and the elimination rate constant from tissues. Rats were administered 3 H-physostigmine (Phy), 100 μg/kg i.v.; and were sacrificed at various times. Tissues were removed and Phy and its metabolites were determined by HPLC. Half-life of Phy in liver and muscle was 24 and 20 min, respectively. ER of Phy in liver was .71 which showed a slight decrease at 10 min. Muscle ER was found to be .347 up to 5 min. Hepatic clearance was calculated to be 23.08 ml/min/kg (34.9% of systemic clearance) and the intrinsic clearance was 83.73 ml/min/kg which indicates that the changes in blood flow to the liver can cause a variation in the systematic clearance. Percentage dose of Phy retained in muscle was maximum and the clearance was 5.2 ml/min/kg suggesting that muscle might be acting as a storage depot for Phy prolonging the pharmacological effects. About 30-40% of radioactivity in the liver could not be washed off by 10% TCA or organic solvents indicating the irreversible binding of drug or metabolite to liver macromolecule

Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

Science.gov (United States)

Sato, Tomohiro; Tamada, Tsutomu; Watanabe, Shigeru; Nishimura, Hirotake; Kanki, Akihiko; Noda, Yasufumi; Higaki, Atsushi; Yamamoto, Akira; Ito, Katsuyoshi

2015-06-01

This study was undertaken to quantify tissue gadolinium (Gd) deposition in hepatorenally impaired rats exposed to gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of inductively coupled plasma mass spectrometry (ICP-MS) and to compare differences in Gd distribution among major organs as possible triggers for nephrogenic systemic fibrosis. Five hepatorenally impaired rats (5/6-nephrectomized, with carbon-tetrachloride-induced liver fibrosis) were injected with Gd-EOB-DTPA. Histological assessment was conducted and Gd content of the skin, liver, kidneys, lungs, heart, spleen, diaphragm, and femoral muscle was measured by inductively coupled plasma mass spectrometry (ICP-MS) at 7 days after last injection. In addition, five renally impaired rats were injected with Gd-EOB-DTPA and the degree of tissue Gd deposition was compared with that in the hepatorenally impaired rats. ICP-MS analysis revealed significantly higher Gd deposition in the kidneys, spleen, and liver (p = 0.009-0.047) in the hepatorenally impaired group (42.6 ± 20.1, 17.2 ± 6.1, 8.4 ± 3.2 μg/g, respectively) than in the renally impaired group (17.2 ± 7.7, 5.4 ± 2.1, 2.8 ± 0.7 μg/g, respectively); no significant difference was found for other organs. In the hepatorenally impaired group, Gd was predominantly deposited in the kidneys, followed by the spleen, liver, lungs, skin, heart, diaphragm, and femoral muscle. Histopathological investigation revealed hepatic fibrosis in the hepatorenally impaired group. Compared with renally impaired rats, tissue Gd deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA was significantly increased in the kidneys, spleen, and liver, probably due to the impairment of the dual excretion pathways of the urinary and biliary systems.

Analysis of plasma-mediated ablation in aqueous tissue

International Nuclear Information System (INIS)

Jiao Jian; Guo Zhixiong

2012-01-01

Plasma-mediated ablation using ultrafast lasers in transparent media such as aqueous tissues is studied. It is postulated that a critical seed free electron density exists due to the multiphoton ionization in order to trigger the avalanche ionization which causes ablation and during the avalanche ionization process the contribution of laser-induced photon ionization is negligible. Based on this assumption, the ablation process can be treated as two separate processes - the multiphoton and avalanche ionizations - at different time stages; so that an analytical solution to the evolution of plasma formation is obtained for the first time. The analysis is applied to plasma-mediated ablation in corneal epithelium and validated via comparison with experimental data available in the literature. The critical seed free-electron density and the time to initiate the avalanche ionization for sub-picosecond laser pulses are analyzed. It is found that the critical seed free-electron density decreases as the pulse width increases, obeying a t p -5.65 rule. This model is further extended to the estimation of crater size in the ablation of tissue-mimic polydimethylsiloxane (PDMS). The results match well with the available experimental measurements.

Metabolic Disturbance in PCOS: Clinical and Molecular Effects on Skeletal Muscle Tissue

Directory of Open Access Journals (Sweden)

Wagner Silva Dantas

2013-01-01

Full Text Available Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

Metabolic disturbance in PCOS: clinical and molecular effects on skeletal muscle tissue.

Science.gov (United States)

Dantas, Wagner Silva; Gualano, Bruno; Rocha, Michele Patrocínio; Barcellos, Cristiano Roberto Grimaldi; dos Reis Vieira Yance, Viviane; Marcondes, José Antonio Miguel

2013-01-01

Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

Impact-induced soft-tissue vibrations associate with muscle activation in human landing movements: An accelerometry and EMG evaluation.

Science.gov (United States)

Fu, Weijie; Wang, Xi; Liu, Yu

2015-01-01

Previous studies have not used neurophysiological methodology to explore the damping effects on induced soft-tissue vibrations and muscle responses. This study aimed to investigate the changes in activation of the musculoskeletal system in response to soft-tissue vibrations with different applied compression conditions in a drop-jump landing task. Twelve trained male participants were instructed to perform drop-jump landings in compression shorts (CS) and regular shorts without compression (control condition, CC). Soft-tissue vibrations and EMG amplitudes of the leg within 50 ms before and after touchdown were collected synchronously. Peak acceleration of the thigh muscles was significantly lower in CS than in CC during landings from 45 or 60 cm and 30 cm heights (p soft-tissue vibration damping was associated with a decrease in muscular activity of the rectus femoris and biceps femoris muscles during drop-jump landings from different heights.

Tissue expression and plasma levels of adrenomedullin in renal cancer patients

DEFF Research Database (Denmark)

Michelsen, Jens; Thiesson, Helle; Walter, Steen

2006-01-01

that AM is increased in CC-RCC tumours and that AM is a plasma biomarker for CC-RCC. Tumours and non-malignant kidney tissue were obtained from patients that underwent unilateral nephrectomy. Blood samples were drawn at the day of surgery, 3-6 days after surgery and 4-5 weeks after surgery. AM m...... conclude that elevated tissue AM is a distinguishing feature of CC-RCC compared with other kidney tumours. Plasma AM is not suited as a tumour marker for this disease....

Air plasma treatment of liquid covered tissue: long timescale chemistry

Science.gov (United States)

Lietz, Amanda M.; Kushner, Mark J.

2016-10-01

Atmospheric pressure plasmas have shown great promise for the treatment of wounds and cancerous tumors. In these applications, the sample is usually covered by a thin layer of a biological liquid. The reactive oxygen and nitrogen species (RONS) generated by the plasma activate and are processed by the liquid before the plasma produced activation reaches the tissue. The synergy between the plasma and the liquid, including evaporation and the solvation of ions and neutrals, is critical to understanding the outcome of plasma treatment. The atmospheric pressure plasma sources used in these procedures are typically repetitively pulsed. The processes activated by the plasma sources have multiple timescales—from a few ns during the discharge pulse to many minutes for reactions in the liquid. In this paper we discuss results from a computational investigation of plasma-liquid interactions and liquid phase chemistry using a global model with the goal of addressing this large dynamic range in timescales. In modeling air plasmas produced by a dielectric barrier discharge over liquid covered tissue, 5000 voltage pulses were simulated, followed by 5 min of afterglow. Due to the accumulation of long-lived species such as ozone and N x O y , the gas phase dynamics of the 5000th discharge pulse are different from those of the first pulse, particularly with regards to the negative ions. The consequences of applied voltage, gas flow, pulse repetition frequency, and the presence of organic molecules in the liquid on the gas and liquid reactive species are discussed.

Astaxanthin Supplementation Delays Physical Exhaustion and Prevents Redox Imbalances in Plasma and Soleus Muscles of Wistar Rats

Directory of Open Access Journals (Sweden)

Tatiana G. Polotow

2014-12-01

Full Text Available Astaxanthin (ASTA is a pinkish-orange carotenoid commonly found in marine organisms, especially salmon. ASTA is a powerful antioxidant and suggested to provide benefits for human health, including the inhibition of LDL oxidation, UV-photoprotection, and prophylaxis of bacterial stomach ulcers. Exercise is associated to overproduction of free radicals in muscles and plasma, with pivotal participation of iron ions and glutathione (GSH. Thus, ASTA was studied here as an auxiliary supplement to improve antioxidant defenses in soleus muscles and plasma against oxidative damage induced by exhaustive exercise. Long-term 1 mg ASTA/kg body weight (BW supplementation in Wistar rats (for 45 days significantly delayed time to exhaustion by 29% in a swimming test. ASTA supplementation increased scavenging/iron-chelating capacities (TEAC/FRAP and limited exercise-induced iron overload and its related pro-oxidant effects in plasma of exercising animals. On the other hand, ASTA induced significant mitochondrial Mn-dependent superoxide dismutase and cytosolic glutathione peroxidase antioxidant responses in soleus muscles that, in turn, increased GSH content during exercise, limited oxidative stress, and delayed exhaustion. We also provided significant discussion about a putative “mitochondrial-targeted” action of ASTA based on previous publications and on the positive results found in the highly mitochondrial populated (oxidative-type soleus muscles here.

Resistance exercise-induced fluid shifts: change in active muscle size and plasma volume

Science.gov (United States)

Ploutz-Snyder, L. L.; Convertino, V. A.; Dudley, G. A.

1995-01-01

The purpose of this study was to test the hypothesis that the reduction in plasma volume (PV) induced by resistance exercise reflects fluid loss to the extravascular space and subsequently selective increase in cross-sectional area (CSA) of active but not inactive skeletal muscle. We compared changes in active and inactive muscle CSA and PV after barbell squat exercise. Magnetic resonance imaging (MRI) was used to quantify muscle involvement in exercise and to determine CSA of muscle groups or individual muscles [vasti (VS), adductor (Add), hamstring (Ham), and rectus femoris (RF)]. Muscle involvement in exercise was determined using exercise-induced contrast shift in spin-spin relaxation time (T2)-weighted MR images immediately postexercise. Alterations in muscle size were based on the mean CSA of individual slices. Hematocrit, hemoglobin, and Evans blue dye were used to estimate changes in PV. Muscle CSA and PV data were obtained preexercise and immediately postexercise and 15 and 45 min thereafter. A hierarchy of muscle involvement in exercise was found such that VS > Add > Ham > RF, with the Ham and RF showing essentially no involvement. CSA of the VS and Add muscle groups were increased 10 and 5%, respectively, immediately after exercise in each thigh with no changes in Ham and RF CSA. PV was decreased 22% immediately following exercise. The absolute loss of PV was correlated (r2 = 0.75) with absolute increase in muscle CSA immediately postexercise, supporting the notion that increased muscle size after resistance exercise reflects primarily fluid movement from the vascular space into active but not inactive muscle.

Contribution of skeletal muscle and adipose tissue to adrenaline-induced thermogenesis in man

DEFF Research Database (Denmark)

Simonsen, L; Stallknecht, B; Bülow, J

1993-01-01

Elevated plasma adrenaline is known to increase whole body energy expenditure. We studied the thermogenic effect and the effects on substrate utilization in man during infusion of adrenaline. Two series were performed: in one series skeletal muscle metabolism was investigated and in another series......% of the whole body adrenaline-induced thermogenesis....

Comparison of serum vaspin levels and vaspin expression in adipose tissue and smooth muscle tissue in pregnant women with and without gestational diabetes.

Science.gov (United States)

Tang, Yuping; Qiao, Ping; Qu, Xiaoxian; Bao, Yirong; Li, Yuhong; Liao, Yini; Ying, Hao

2017-10-01

Vaspin is associated with metabolic parameters and insulin resistance. However, the expression of vaspin in visceral adipose tissue (VAT) in pregnant women with gestational diabetes mellitus (GDM) has not been fully explored, and the contribution of vaspin to the biological mechanisms underlying GDM remains unclear. This study aimed to compare circulating vaspin levels and its expression in different insulin target tissues including subcutaneous adipose tissue (SAT), VAT and smooth muscle tissue (SMT) in pregnant women with and without GDM. A total of 37 women with GDM (GDM group) and 37 normal pregnant women (control group) were selected. Fasting plasma glucose (FPG), fasting insulin (FINS) and serum vaspin levels were quantified at term, and homeostasis model of assessment2-insulin resistance (HOMA2-IR) values were calculated. RT-qPCR and Western blotting were used to measure mRNA and protein levels of vaspin in VAT, SAT and SMT of 15 GDM women and normal pregnant women. In the GDM group, serum vaspin concentrations were significantly higher than in the control group. Serum vaspin levels were positively correlated with HOMA2-IR in the GDM group but not in the control group. In the GDM group, vaspin mRNA and protein expression levels in SAT and VAT were both significantly higher than in controls, but no difference was found in SMT. Moreover, relative mRNA but not protein expression levels of vaspin in SAT were highest among the three tissues in both groups. Circulating vaspin levels and expression of vaspin in SAT and VAT were higher in GDM women than in normal pregnant women. However, the specific role of vaspin from SAT and VAT in the pathogenesis of GDM needs further study. © 2017 John Wiley & Sons Ltd.

Air plasma treatment of liquid covered tissue: long timescale chemistry

International Nuclear Information System (INIS)

Lietz, Amanda M; Kushner, Mark J

2016-01-01

Atmospheric pressure plasmas have shown great promise for the treatment of wounds and cancerous tumors. In these applications, the sample is usually covered by a thin layer of a biological liquid. The reactive oxygen and nitrogen species (RONS) generated by the plasma activate and are processed by the liquid before the plasma produced activation reaches the tissue. The synergy between the plasma and the liquid, including evaporation and the solvation of ions and neutrals, is critical to understanding the outcome of plasma treatment. The atmospheric pressure plasma sources used in these procedures are typically repetitively pulsed. The processes activated by the plasma sources have multiple timescales—from a few ns during the discharge pulse to many minutes for reactions in the liquid. In this paper we discuss results from a computational investigation of plasma–liquid interactions and liquid phase chemistry using a global model with the goal of addressing this large dynamic range in timescales. In modeling air plasmas produced by a dielectric barrier discharge over liquid covered tissue, 5000 voltage pulses were simulated, followed by 5 min of afterglow. Due to the accumulation of long-lived species such as ozone and N x O y , the gas phase dynamics of the 5000th discharge pulse are different from those of the first pulse, particularly with regards to the negative ions. The consequences of applied voltage, gas flow, pulse repetition frequency, and the presence of organic molecules in the liquid on the gas and liquid reactive species are discussed. (paper)

Loss of mass and performance in skeletal muscle tissue: a continuum model

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Giantesio Giulia

2018-02-01

Full Text Available We present a continuum hyperelastic model which describes the mechanical response of a skeletal muscle tissue when its strength and mass are reduced by aging. Such a reduction is typical of a geriatric syndrome called sarcopenia. The passive behavior of the material is described by a hyperelastic, polyconvex, transversely isotropic strain energy function, and the activation of the muscle is modeled by the so called active strain approach. The loss of ability of activating of an elder muscle is then obtained by lowering of some percentage the active part of the stress, while the loss of mass is modeled through a multiplicative decomposition of the deformation gradient. The obtained stress-strain relations are graphically represented and discussed in order to study some of the effects of sarcopenia.

Mg(2+,ATP-dependent plasma membrane calcium pump of smooth muscle cells. ІІ. Regulation of activity

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T. О. Veklich

2015-04-01

Full Text Available Plasma membrane Ca2+-pump is one of key proteins, which takes part in Ca2+ exchange in smooth muscle cells. It has a lot of diverse functions from control of basal cytoplasmal Ca2+ concentration to regulation of proteins involved in Ca2+-dependent signal pathway. Ca2+ pump function is often depen­dent on the isoform or even form of alternative splicing. Allowing for a variety of Ca2+-pump functions and properties, which were reviewed in detail in the first part of our review article cycle (Ukr. Biochem. J., 2015; 87(1, the precise control of the mentioned pump activity is very important for cell functioning­. The other part of this article is dedicated to different regulation factors of smooth muscle plasma membrane Ca2+-pump activity: endogenous and exo­genous, biotic and abiotic factors. Special attention is given to literature data and own results about design and the search of selective plasma membrane Ca2+-pump inhibitor which would allow examining its functioning in smooth muscle cells more meticulously.

Immunohistochemical and Morphofunctional Studies of Skeletal Muscle Tissues with Electric Nerve Stimulation by In Vivo Cryotechnique

International Nuclear Information System (INIS)

Fukasawa, Yuki; Ohno, Nobuhiko; Saitoh, Yurika; Saigusa, Takeshi; Arita, Jun; Ohno, Shinichi

2015-01-01

In this study, morphological and immunohistochemical alterations of skeletal muscle tissues during persistent contraction were examined by in vivo cryotechnique (IVCT). Contraction of gastrocnemius muscles was induced by sciatic nerve stimulation. The IVCT was performed immediately, 3 min or 10 min after the stimulation start. Prominent ripples of muscle fibers or wavy deformation of sarcolemma were detected immediately after the stimulation, but they gradually diminished to normal levels during the stimulation. The relative ratio of sarcomere and A band lengths was the highest in the control group, but it immediately decreased to the lowest level and then gradually recovered at 3 min or 10 min. Although histochemical intensity of PAS reaction was almost homogeneous in muscle tissues of the control group or immediately after the stimulation, it decreased at 3 min or 10 min. Serum albumin was immunolocalized as dot-like patterns within some muscle fibers at 3 min stimulation. These patterns became more prominent at 10 min, and the dots got larger and saccular in some sarcoplasmic regions. However, IgG1 and IgM were immunolocalized in blood vessels under nerve stimulation conditions. Therefore, IVCT was useful to capture the morphofunctional and metabolic changes of heterogeneous muscle fibers during the persistent contraction

High-speed photography of plasma during excimer laser-tissue interaction

International Nuclear Information System (INIS)

Murray, Andrea K; Dickinson, Mark R

2004-01-01

During high fluence laser-tissue interaction, ablation of tissue occurs, debris is removed from the ablation site and is then ejected at high velocity. This debris may be observed as a combination of luminous plasma and non-luminous plume, both of which have the potential to shield the ablation site. This study examined the role of ablation debris in shielding the tissue and determined its effects on the ablation rate over a range of laser pulse energies, pulse repetition rates and pulse numbers for dentine; the velocity differences between hard and soft tissues were also examined. High-speed photography was carried out at up to 1 x 10 8 frames per second. A maximum velocity of 2.58 ± 0.52 x 10 4 m s -1 was recorded for dentine debris within the first 10 ns following ejection. The maximum duration of tissue shielding due to a single pulse, determined by attenuation of a probe beam, was found to be ∼7 ms, ∼80 μs of which was due to luminous plasma and the remainder due to the non-luminous plume

Neck muscle atrophy and soft-tissue fibrosis after neck dissection and postoperative radiotherapy for oral cancer

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Kim, Jinu; Shin, Eun Seow; Kim, Jeong Eon; Yoon, Sang Pil [Jeju National University School of Medicine, Jeju (Korea, Republic of); Kim, Young Suk [Dept. of Radiation Oncology, Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of)

2015-12-15

Late complications of head and neck cancer survivors include neck muscle atrophy and soft-tissue fibrosis. We present an autopsy case of neck muscle atrophy and soft-tissue fibrosis (sternocleidomastoid, omohyoid, digastric, sternohyoid, sternothyroid, and platysma muscles) within the radiation field after modified radical neck dissection type I and postoperative radiotherapy for floor of mouth cancer. A 70-year-old man underwent primary tumor resection of the left floor of mouth, left marginal mandibulectomy, left modified radical neck dissection type I, and reconstruction with a radial forearm free flap. The patient received adjuvant radiotherapy. The dose to the primary tumor bed and involved neck nodes was 63 Gy in 35 fractions over 7 weeks. Areas of subclinical disease (left lower neck) received 50 Gy in 25 fractions over 5 weeks. Adjuvant chemotherapy was not administered.

Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

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Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

2016-10-01

Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases.

The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue

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Larsen, Steen; Danielsen, J H; Søndergård, Stine Dam

2015-01-01

High-intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurance training [60-90% of maximal oxygen uptake (VO2peak )]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT...... of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximal fat oxidation in either skeletal muscle or adipose tissue. Km (app) for octanoyl carnitine or palmitoyl carnitine were similar after training in skeletal...... muscle and adipose tissue. Maximal OXPHOS capacity with complex I- and II-linked substrates was increased after training in skeletal muscle but not in adipose tissue. In conclusion, 6 weeks of HIT increased VO2peak . Mitochondrial content and mitochondrial OXPHOS capacity were increased in skeletal...

Comparison of tissue damage caused by various laser systems with tissue tolerable plasma by light and laser scan microscopy

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Vandersee, Staffan; Lademann, Jürgen; Richter, Heike; Patzelt, Alexa; Lange-Asschenfeldt, Bernhard

2013-01-01

Tissue tolerable plasma (TTP) represents a novel therapeutic method with promising capabilities in the field of dermatological interventions, in particular disinfection but also wound antisepsis and regeneration. The energy transfer by plasma into living tissue is not easily educible, as a variety of features such as the medium’s actual molecule-stream, the ions, electrons and free radicals involved, as well as the emission of ultraviolet, visible and infrared light contribute to its increasingly well characterized effects. Thus, relating possible adversary effects, especially of prolonged exposure to a single component of the plasma’s mode of action, is difficult. Until now, severe adverse events connected to plasma exposure have not been reported when conducted according to existing therapeutic protocols. In this study, we have compared the tissue damage-potential of CO 2 and dye lasers with TTP in a porcine model. After exposure of pig ear skin to the three treatment modalities, all specimens were examined histologically and by means of laser scan microscopy (LSM). Light microscopical tissue damage could only be shown in the case of the CO 2 laser, whereas dye laser and plasma treatment resulted in no detectable impairment of the specimens. In the case of TTP, LSM examination revealed only an impairment of the uppermost corneal layers of the skin, thus stressing its safety when used in vivo. (letter)

Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss

DEFF Research Database (Denmark)

Bruun, Jens M; Stallknecht, Bente; Helge, Jørn W

2007-01-01

, and skeletal muscle (SM) in obese subjects after weight loss. SUBJECTS AND METHODS: At baseline, plasma and AT IL-18 in 23 obese subjects were compared with that in 12 lean subjects. The obese subjects were submitted to a 15-week life-style intervention (hypocaloric diet and daily exercise) after which plasma...

Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear Cells and Platelet-Rich Plasma.

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Seffer, Istvan; Nemeth, Zoltan

2017-06-01

Peripheral blood mononuclear cells (PBMCs) are multipotent, and plasma contains growth factors involving tissue regeneration. We hypothesized that transplantation of PBMC-plasma will promote the recovery of paralyzed facial muscles in Bell palsy. This case report describes the effects of PBMC-plasma transplantations in a 27-year-old female patient with right side Bell palsy. On the affected side of the face, the treatment resulted in both morphological and functional recovery including voluntary facial movements. These findings suggest that PBMC-plasma has the capacity of facial muscle regeneration and provides a promising treatment strategy for patients suffering from Bell palsy or other neuromuscular disorders.

Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development.

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Migliaccio, Silvia; Greco, Emanuela A; Wannenes, Francesca; Donini, Lorenzo M; Lenzi, Andrea

2014-01-01

The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.

Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue

DEFF Research Database (Denmark)

Grunnet, Louise G; Nilsson, Emma; Ling, Charlotte

2009-01-01

Objective. Common variants in FTO (the fat-mass and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and non-genetic regulation of FTO mRNA in skeletal muscle...... and adipose tissue, and their influence on in vivo glucose and fat metabolism. Research Design and Methods. The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years......) and elderly (58-66 years) non-diabetic twins examined by a hyperinsulinemic euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n=226) and skeletal muscle biopsies (n=158). Results. Heritability of FTO expression in both tissues was low, and FTO...

[Determination of acyclovir in mouse plasma and tissues by reversed-phase high performance liquid chromatography].

Science.gov (United States)

Xu, Y; Zhou, S W; Tang, J L; Huang, L Q

2001-11-01

The aim of this study was to establish an high performance liquid chromatographic method for determining acyclovir (ACV) concentration in mouse plasma and tissues. A solution of 0.25 mL 60 g/L perchloric acid and 0.25 mL acetonitrile was added into 0.2 mL plasma or 0.2 g tissues to precipitate proteins. Following centrifugation, the supernatant obtained was injected into a reversed-phase column. Operating conditions were Hypersil ODS column(250 mm x 4.6 mm i.d., 5 microns), methanol-water-acetic acid(1:99:0.5, volume ratio) solution as mobile phase at a flow rate of 1.5 mL/min, UV detection at 252 nm. The detection limit of ACV concentration in plasma was 20 micrograms/L and that in tissues was 50 ng/g. The standard curves for ACV were linear in plasma and homogenate of tissues (r > 0.99). The precision of the method was good and the recoveries of ACV were higher than 97.5%. So this method is rapid, accurate and convenient for determination of ACV concentrations in plasma and tissues.

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

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Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

2015-01-01

Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

YKL-40 tissue expression and plasma levels in patients with ovarian cancer

International Nuclear Information System (INIS)

Høgdall, Estrid VS; Christensen, Lise H; Ringsholt, Merete; Høgdall, Claus K; Christensen, Ib Jarle; Johansen, Julia S; Kjaer, Susanne K; Blaakaer, Jan; Ostenfeld-Møller, Lene; Price, Paul A

2009-01-01

YKL-40 (chitinase-3-like-1) is a member of 'mammalian chitinase-like proteins'. The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. YKL-40 protein expression was determined by immunohistochemistry in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor cell expression was higher in OC than in borderline tumors (p = 0.001), and associated with FIGO stage (p < 0.0001) and histological subtype (p = 0.0009). Positive YKL-40 expression (≥ 5% staining) was not associated with reduced survival. Plasma YKL-40 was also higher in patients with OC than in patients with borderline tumors (p < 0.0001), and it was positively correlated to serum CA-125 (p < 0.0001) and FIGO stage (p = 0.0001). Univariate Cox analysis of plasma YKL-40 showed association with overall survival (p < 0.0001). Multivariate Cox analysis, including plasma YKL-40, serum CA125, FIGO stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40–3.25, p = 0.0004). YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic biomarker in patients with OC

The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

Science.gov (United States)

Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

2017-01-01

The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

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...

Infiltration of plasma rich in growth factors enhances in vivo angiogenesis and improves reperfusion and tissue remodeling after severe hind limb ischemia.

Science.gov (United States)

Anitua, Eduardo; Pelacho, Beatriz; Prado, Roberto; Aguirre, José Javier; Sánchez, Mikel; Padilla, Sabino; Aranguren, Xabier L; Abizanda, Gloria; Collantes, María; Hernandez, Milagros; Perez-Ruiz, Ana; Peñuelas, Ivan; Orive, Gorka; Prosper, Felipe

2015-03-28

PRGF is a platelet concentrate within a plasma suspension that forms an in situ-generated fibrin-matrix delivery system, releasing multiple growth factors and other bioactive molecules that play key roles in tissue regeneration. This study was aimed at exploring the angiogenic and myogenic effects of PRGF on in vitro endothelial cells (HUVEC) and skeletal myoblasts (hSkMb) as well as on in vivo mouse subcutaneously implanted matrigel and on limb muscles after a severe ischemia. Human PRGF was prepared and characterized. Both proliferative and anti-apoptotic responses to PRGF were assessed in vitro in HUVEC and hSkMb. In vivo murine matrigel plug assay was conducted to determine the angiogenic capacity of PRGF, whereas in vivo ischemic hind limb model was carried out to demonstrate PRGF-driven vascular and myogenic regeneration. Primary HUVEC and hSkMb incubated with PRGF showed a dose dependent proliferative and anti-apoptotic effect and the PRGF matrigel plugs triggered an early and significant sustained angiogenesis compared with the control group. Moreover, mice treated with PRGF intramuscular infiltrations displayed a substantial reperfusion enhancement at day 28 associated with a fibrotic tissue reduction. These findings suggest that PRGF-induced angiogenesis is functionally effective at expanding the perfusion capacity of the new vasculature and attenuating the endogenous tissue fibrosis after a severe-induced skeletal muscle ischemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Laminin α2 chain-deficiency is associated with microRNA deregulation in skeletal muscle and plasma

Directory of Open Access Journals (Sweden)

Johan eHolmberg

2014-07-01

Full Text Available MicroRNAs (miRNAs are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A. MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs are markedly elevated in laminin α2 chain-deficient mice and partially normalized in response to proteasome inhibition therapy. Altogether, our data suggest important roles for miRNAs in MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as promising biomarkers for the progression of MDC1A.

A critical evaluation of body composition modalities used to assess adipose and skeletal muscle tissue in cancer.

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Di Sebastiano, Katie M; Mourtzakis, Marina

2012-10-01

The majority of cancer patients experience some form of body composition change during the disease trajectory. For example, breast cancer patients undergoing chemotherapy and prostate cancer patients undergoing androgen deprivation therapy gain fat and lose skeletal muscle, which are associated with increased risk of cancer recurrence and clinical comorbidities. In contrast, advanced cancer patients, such as lung and colorectal cancer patients, experience symptoms of cancer cachexia (accelerated loss of skeletal muscle with or without adipose tissue loss), which are associated with decreased treatment response and poorer survival rates in advanced cancers. The heterogeneity of body composition features and their diverse implications across different cancer populations supports the need for accurate quantification of muscle and adipose tissue. Use of appropriate body composition modalities will facilitate an understanding of the complex relationship between body composition characteristics and clinical outcomes. This will ultimately support the development and evaluation of future therapeutic interventions that aim to counter muscle loss and fat gain in cancer populations. Despite the various metabolic complications that may confound the accurate body composition measurement in cancer patients (i.e., dehydration may confound lean tissue measurement), there are no guidelines for selecting the most appropriate modalities to make these measurements. In this review we outline specific considerations for choosing the most optimal approaches of lean and adipose tissue measurements among different cancer populations. Anthropometric measures, bioelectrical impedance analysis, air displacement plethysmography, dual-energy X-ray absorptiometry, computed tomography, and magnetic resonance imaging will be discussed.

Plasma luminescence feedback control system for precise ultrashort pulse laser tissue ablation

Science.gov (United States)

Kim, Beop-Min; Feit, Michael D.; Rubenchik, Alexander M.; Gold, David M.; Darrow, Christopher B.; Marion, John E., II; Da Silva, Luiz B.

1998-05-01

Plasma luminescence spectroscopy was used for precise ablation of bone tissue without damaging nearby soft tissue using an ultrashort pulse laser. Strong contrast of the luminescence spectra between bone marrow and spinal cord provided the real time feedback control so bone tissue is selectively ablated while preserving the spinal cord.

The Effects of Environmental Factors on Smooth Muscle Cells Differentiation from Adipose-Derived Stem Cells and Esophagus Tissues Engineering

DEFF Research Database (Denmark)

Wang, Fang

Adipose-derived stem cells (ASCs) are increasingly being used for regenerative medicine and tissue engineering. Smooth muscle cells (SMCs) can be differentiated from ASCs. Oxygen is a key factor influencing the stem cell differentiation. Tissue engineered esophagus has been a preferred solution...... of esophagus was studied. Our results showed that both SMCs and ASCs could attach on the porcine esophageal acellular matrix (EAM) scaffold in vitro after 24 hours and survive until 7 days. Thus ASCs might be a substitute for SMCs in the construction of tissue engineered esophageal muscle layer....

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.

Characterization of tissue metabolism of thyroid hormones in very premature infants

International Nuclear Information System (INIS)

Pavelka, S.; Kopecky, J.; Brauner, P.

1998-01-01

Thyroid status was characterized in very preterm infants (gestational age 23-32 wk; n = 61) from birth through day 14; in those infants who died within 16 days of delivery (n = 10) it was also correlated with the metabolism of thyroid hormones in peripheral tissues (brain, liver, kidney, skeletal muscle, and different localities of adipose tissue). The results obtained support the view that peripheral tissues of very premature infants are involved in local generation of triiodothyronine (T 3 ) and inactivation of thyroid hormones, but do not represent a major source of circulating T 3 . In this study observations on postnatal development of plasma thyroid hormone levels in normal and critically ill premature neonates are presented. Enzyme activities of all three types of iodothyronine deiodinases were followed in autopsy samples from brain, liver, kidney, muscle, and adipose tissue depots, to better characterize the relationships between peripheral metabolism of thyroid hormones and thyroid status in critically ill very preterm newborns. Plasma concentrations of total T 3 , total T 4 , and total rT 3 were estimated by competitive radioimmunoassay. Plasma TSH concentrations were measured by microparticle enzyme immunoassay. Measurable activities of deiodinases of type I, II and II were detected post mortem in all tissue samples, except for type II activity in kidney. No correlation between postnatal age and the enzyme activities was found in in different tissues in the group of infants who died by 16 days of age. All activities were the highest in liver and differed significantly in particular tissues. Obtained results suggest tat, in contrast to adults, iodothyronine metabolism in peripheral tissues of premature newborns seems to be dominated by thyroid hormones inactivation, and T 3 production mainly for local use inside tissues. (authors)

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.

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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.

Plasma and tissue oxidative stress index in patients with rheumatic and degenerative heart valve disease.

Science.gov (United States)

Rabus, Murat; Demirbağ, Recep; Sezen, Yusuf; Konukoğlu, Oğuz; Yildiz, Ali; Erel, Ozcan; Zeybek, Rahmi; Yakut, Cevat

2008-12-01

We investigated whether patients with rheumatic and degenerative heart valve disease (HVD) differed with regard to plasma and tissue oxidative stress index (OSI). The study included 56 patients who underwent valve replacement due to rheumatic (n=32; 15 males; mean age 47+/-10 years) and degenerative (n=24; 13 males; mean age 55+/-12 years) HVD. Plasma and tissue total oxidative status (TOS) and total antioxidative capacity (TAC) levels were measured and OSI was calculated. Patients with degenerative HVD had significantly higher age, increased interventricular septum thickness, and higher frequency of aortic stenosis, whereas the incidence of mitral stenosis was higher in patients with rheumatic HVD (p0.05). Tissue TAC was significantly lower in patients with rheumatic HVD (p=0.027), whereas tissue TOS and OSI were similar between the two HVD groups (p>0.05). In bivariate analysis, plasma OSI did not show any correlation with clinical, laboratory, and echocardiographic variables (p>0.05). Our data show that plasma and tissue OSI levels are similar in patients with rheumatic and degenerative HVD.

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

Intramuscular Connective Tissue Differences in Spastic and Control Muscle: A Mechanical and Histological Study

Science.gov (United States)

de Bruin, Marije; Smeulders, Mark J.; Kreulen, Michiel; Huijing, Peter A.; Jaspers, Richard T

2014-01-01

Cerebral palsy (CP) of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU) from CP patients (n = 29) and healthy controls (n = 10). The sarcomere slack length (mean 2.5 µm, SEM 0.05) and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190) in spastic muscle than in controls (2572 µm2, SEM 322). However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold), i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23) did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients. PMID:24977410

Tissue-Engineered Vascular Rings from Human iPSC-Derived Smooth Muscle Cells

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Biraja C. Dash

2016-07-01

Full Text Available There is an urgent need for an efficient approach to obtain a large-scale and renewable source of functional human vascular smooth muscle cells (VSMCs to establish robust, patient-specific tissue model systems for studying the pathogenesis of vascular disease, and for developing novel therapeutic interventions. Here, we have derived a large quantity of highly enriched functional VSMCs from human induced pluripotent stem cells (hiPSC-VSMCs. Furthermore, we have engineered 3D tissue rings from hiPSC-VSMCs using a facile one-step cellular self-assembly approach. The tissue rings are mechanically robust and can be used for vascular tissue engineering and disease modeling of supravalvular aortic stenosis syndrome. Our method may serve as a model system, extendable to study other vascular proliferative diseases for drug screening. Thus, this report describes an exciting platform technology with broad utility for manufacturing cell-based tissues and materials for various biomedical applications.

Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish (Danio rerio) by a waterborne uranium exposure

International Nuclear Information System (INIS)

Barillet, Sabrina; Larno, Valerie; Floriani, Magali; Devaux, Alain; Adam-Guillermin, Christelle

2010-01-01

Experiments on adult zebrafish (Danio rerio) were conducted to assess histopathological effects induced on gill, muscle, and gonadal tissues after waterborne uranium exposure. Although histopathology is often employed as a tool for the detection and assessment of xenobiotic-mediated effects in aquatic organisms, few studies have been dedicated to the investigation of histopathological consequences of uranium exposure in fish. Results showed that gill tissue architecture was markedly disrupted. Major symptoms were alterations of the secondary lamellae epithelium (from extensive oedema to desquamation), hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle histology was also affected. Degeneration and disorganization of myofibrillar sarcomeric pattern as well as abnormal localization of mitochondria within muscle and altered endomysial sheaths were observed. Morphological alterations of spermatozoa within the gonadal tissue were also noticed. This study demonstrated that uranium exposure induced a variety of histological impairments in fish, supporting environmental concerns when uranium contaminates aquatic systems.

Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish (Danio rerio) by a waterborne uranium exposure

Energy Technology Data Exchange (ETDEWEB)

Barillet, Sabrina, E-mail: sabrina.barillet@free.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Larno, Valerie, E-mail: valerie.larno@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Floriani, Magali, E-mail: magali.floriani@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Devaux, Alain, E-mail: alain.devaux@entpe.fr [INRA, EFPA Department, 54280, Champenoux and Environmental Science Laboratory, ENTPE, 69518 Vaulx en Velin cedex (France); Adam-Guillermin, Christelle, E-mail: christelle.adam-guillermin@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France)

2010-11-01

Experiments on adult zebrafish (Danio rerio) were conducted to assess histopathological effects induced on gill, muscle, and gonadal tissues after waterborne uranium exposure. Although histopathology is often employed as a tool for the detection and assessment of xenobiotic-mediated effects in aquatic organisms, few studies have been dedicated to the investigation of histopathological consequences of uranium exposure in fish. Results showed that gill tissue architecture was markedly disrupted. Major symptoms were alterations of the secondary lamellae epithelium (from extensive oedema to desquamation), hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle histology was also affected. Degeneration and disorganization of myofibrillar sarcomeric pattern as well as abnormal localization of mitochondria within muscle and altered endomysial sheaths were observed. Morphological alterations of spermatozoa within the gonadal tissue were also noticed. This study demonstrated that uranium exposure induced a variety of histological impairments in fish, supporting environmental concerns when uranium contaminates aquatic systems.

Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys

International Nuclear Information System (INIS)

Ferrara, E.A.; Oishi, J.S.; Wannemacher, R.W. Jr.; Stephen, E.L.

1981-01-01

Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of [14C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected [14C]ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats

The mechanism of plasma-assisted penetration of NO2- in model tissues

Science.gov (United States)

He, Tongtong; Liu, Dingxin; Liu, Zhijie; Liu, Zhichao; Li, Qiaosong; Rong, Mingzhe; Kong, Michael G.

2017-11-01

Cold atmospheric plasmas are reportedly capable of enhancing the percutaneous absorption of drugs, which is a development direction of plasma medicine. This motivated us to study how the enhancement effect was realized. In this letter, gelatin gel films were used as surrogates of human tissues, NaNO2 was used as a representative of small-molecule drugs, and cross-field and linear-field plasma jets were used for the purpose of enhancing the penetration of NaNO2 through the gelatin gel films. The permeability of gelatin gel films was quantified by measuring the NO2- concentration in water which was covered by those films. It was found that the gas flow and electric field of cold plasmas played a crucial role in the permeability enhancement of the model tissues, but the effect of gas flow was mainly confined in the surface layer, while the effect of the electric field was holistic. Those effects might be attributed to the localized squeezing of particles by gas flow and the weakening of the ion-dipole interaction by the AC electric field. The enhancement effect decreases with the increasing mass fraction of gelatin because the macromolecules of gelatin could significantly hinder the penetration of small molecules in the model tissues.

Plasma and tissue osteopontin expression in cutaneous lichen planus and its relation to metabolic syndrome

International Nuclear Information System (INIS)

Awad, M.A.I.

2015-01-01

Lichen planus (LP) is a chronic inflammatory disease that affects the skin, mucous membranes and appendages. Although its pathogenesis is still unclear, some studies showed that autoreactive cytotoxic T lymphocytes are the effector cells which cause degeneration and destruction of keratinocytes. Osteopontin (OPN) is expressed during inflammation by natural killer cells, activated T cells and macrophages and classified as a T-helper type 1 (Th1) cytokine. Plasma OPN has been reported to be a potential clinical marker for prediction of atherosclerosis. The mean values of plasma and tissue OPN in the lesional skin of LP patients were significantly higher than that in the control group (P Values for both plasma and tissue OPN were < 0.001). Correlating levels of plasma OPN in the LP patients to metabolic syndrome parameters showed a statistically significant correlation with dyslipidemia and diabetes mellitus. In conclusion, levels of plasma and tissue OPN were higher in cutaneous lichen planus patients than controls and plasma OPN could be a marker for cardiovascular risk in these patients

Retinol-binding protein 4 in twins: regulatory mechanisms and impact of circulating and tissue expression levels on insulin secretion and action

DEFF Research Database (Denmark)

Ribel-Madsen, Rasmus; Friedrichsen, Martin; Vaag, Allan

2009-01-01

OBJECTIVE: Retinol-binding protein (RBP) 4 is an adipokine of which plasma levels are elevated in obesity and type 2 diabetes. The aims of the study were to identify determinants of plasma RBP4 and RBP4 mRNA expression in subcutaneous adipose tissue (SAT) and skeletal muscle and to investigate...... expression was not associated with circulatory RBP4. CONCLUSIONS: In conclusion, our data indicate that RBP4 levels in plasma, skeletal muscle, and fat may be linked to insulin resistance and type 2 diabetes in a secondary and noncausal manner....

Tissue distribution of 14C-diazepam and its metabolites in rats

International Nuclear Information System (INIS)

Igari, Y.; Sugiyama, Y.; Sawada, Y.; Iga, T.; Hanano, M.

1982-01-01

We have kinetically investigated the tissue distribution of 14 C-diazepam and described the appearance and disappearance of its metabolites (3-hydroxydiazepam, desmethyldiazepam, and oxazepam) following a single iv injection of 14 C-diazepam into rats. Significant amounts of oxazepam were detected in plasma and various tissues in the rat, contrary to previous reports. Concentration-time profiles of diazepam in the main disposing organs (liver, kidney, and lung) and the other organs (brain, heart, and small intestine) indicated that diazepam was distributed rapidly to these organs. Concentration-time profiles of diazepam in the main tissues for drug distribution (skin and adipose) indicated that diazepam was slowly distributed to these tissues, whereas that in muscle, which is also responsible for drug distribution, indicated that diazepam was less rapidly distributed to this tissue. Metabolites appeared in plasma and various tissues or organs immediately after iv injection of diazepam. Metabolites levels in plasma and various tissues or organs were significantly lower than that of diazepam except for liver and small intestine, where metabolites levels were higher compared to that of diazepam and metabolites exhibited a considerable persistence

Physical and Chemical Changes in Fresh Chilled Muscle Tissue of Common Carp (Cyprinus carpio L. Packed in a Modified Atmosphere

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F. Ježek

2007-01-01

Full Text Available The aim of the study was to monitor the course of physical and chemical changes taking place in stored fresh chilled muscle tissue of carp packed in modified atmosphere (MAP, and to determine its shelf life. Samples of muscle tissue of common carp (Cyprinus carpio, L. were packed in MAP (80% O2, 20% CO2 and stored for 15 days at +2 ± 2 °C max. During the storage period, O2 level in packs decreased from 78.7 ± 0.39% (day 1 to 63.8 ± 1.30% (day 15. Decrease in O2 in packs between storage days 7 and 9 was highly significant (p -1 (day 15. Hydrolytic lipid decomposition (FFA was more intensive in carp muscle tissue (2.09 ± 1.07% total lipid as oleic acid than in carp skin (1.01 ± 0.31% total lipid as oleic acid (day 15. Lipid oxidation (PV in skin showed differences from lipid oxidation in muscle tissue. Oxidation processes in muscle correlated positively with the length of storage (r = 0.90. Over the storage period, peroxide levels increased from 2.58 ± 1.19 mekv O2 kg-1 (day 1 to 6.76 ± 1.78 mekv O2 kg-1 (day 15. Because of low TVBN levels in muscle tissue, shelf life was limited mainly by sensory changes (green discoloration, odour deviations, slime production, which were observed from storage day 9 onwards. It was found that the maximum shelf life of carp packed in MAP (80% O2, 20% CO2 was 7 days. The optimum parameter to determine the remaining shelf life of common carp muscle tissue stored at +2 ± 2 °C max is the TVBN level. As concerns shelf life, TVBN levels in carp muscle should not exceed 15 mg 100 g-1. This level of TVBN (max. 15 mg 100 g-1 for carp (MAP 80% O2, 20% CO2 is much more lower in comparison with levels TVBN (max 25 - 35 mg 100 g-1 which have been determined by Commission Regulation (EC No. 2074/2005 for sea fish. For that reason we suggest to amplify the study by other monitoring (higher number of samples, various breeds of carp in different weight categories for all the year. On the basis of these analyses the level

Could a functional artificial skeletal muscle be useful in muscle wasting?

Science.gov (United States)

Fuoco, Claudia; Cannata, Stefano; Gargioli, Cesare

2016-05-01

Regardless of the underlying cause, skeletal muscle wasting is detrimental for a person's life quality, leading to impaired strength, locomotion, and physiological activity. Here, we propose a series of studies presenting tissue engineering-based approaches to reconstruct artificial muscle in vitro and in vivo. Skeletal muscle tissue engineering is attracting more and more attention from scientists, clinicians, patients, and media, thanks to the promising results obtained in the last decade with animal models of muscle wasting. The use of novel and refined biomimetic scaffolds mimicking three-dimensional muscle environment, thus supporting cell survival and differentiation, in combination with well characterized myogenic stem/progenitor cells, revealed the noteworthy potential of these technologies for creating artificial skeletal muscle tissue. In vitro, the production of three-dimensional muscle structures offer the possibility to generate a drug-screening platform for patient-specific pharmacological treatment, opening new frontiers in the development of new compounds with specific therapeutic actions. In vivo, three-dimensional artificial muscle biomimetic constructs offer the possibility to replace, in part or entirely, wasted muscle by means of straight reconstruction and/or by enhancing endogenous regeneration. Reports of tissue engineering approaches for artificial muscle building appeared in large numbers in the specialized press lately, advocating the suitability of this technology for human application upon scaling up and a near future applicability for medical care of muscle wasting. http://links.lww.com/COCN/A9

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

Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats.

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Anette I Öberg

Full Text Available BACKGROUND: There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin, plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. CONCLUSIONS/SIGNIFICANCE: Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes.

Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle.

Science.gov (United States)

Moore, Stephanie N; Hawley, Gregory D; Smith, Emily N; Mignemi, Nicholas A; Ihejirika, Rivka C; Yuasa, Masato; Cates, Justin M M; Liu, Xulei; Schoenecker, Jonathan G

2016-01-01

Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary to discriminate

Exercise-induced increase in glucose transport, GLUT-4, and VAMP-2 in plasma membrane from human muscle

DEFF Research Database (Denmark)

Kristiansen, S; Hargreaves, Mark; Richter, Erik

1996-01-01

contractions may induce trafficking of GLUT-4-containing vesicles via a mechanism similar to neurotransmitter release. Our results demonstrate for the first time exercise-induced translocation of GLUT-4 and VAMP-2 to the plasma membrane of human muscle and increased sarcolemmal glucose transport.......A major effect of muscle contractions is an increase in sarcolemmal glucose transport. We have used a recently developed technique to produce sarcolemmal giant vesicles from human muscle biopsy samples obtained before and after exercise. Six men exercised for 10 min at 50% maximal O2 uptake (Vo2max...

Comparison between IgG and F(ab′)2 polyvalent antivenoms: neutralization of systemic effects induced by Bothrops asper venom in mice, extravasation to muscle tissue, and potential for induction of adverse reactions

OpenAIRE

León Montero, Guillermo; Monge Monge, María; Rojas Umaña, Ermila; Lomonte, Bruno; Gutiérrez, José María

2001-01-01

Whole IgG and F(ab′)2 equine-derived polyvalent (Crotalinae) antivenoms, prepared from the same batch of hyperimmune plasma, were compared in terms of neutralization of the lethal and defibrinating activities induced by Bothrops asper venom, their ability to reach the muscle tissue compartment in envenomated mice, and their potential for the induction of adverse reactions. Both preparations were adjusted to the same potency against the lethal effect of B. asper venom in experiments involving ...

Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

Science.gov (United States)

Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

2006-03-01

Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

Finite-element simulation of blood perfusion in muscle tissue during compression and sustained contraction

NARCIS (Netherlands)

Vankan, W.J.; Huyghe, J.M.R.J.; Slaaf, D.W.; Donkelaar, van C.C.; Drost, M.R.; Janssen, J.D.; Huson, A.

1997-01-01

Mechanical interaction between tissue stress and blood perfusion in skeletal muscles plays an important role in blood flow impediment during sustained contraction. The exact mechanism of this interaction is not clear, and experimental investigation of this mechanism is difficult. We developed a

Tissue to plasma capillary permeability of 131I-albumin in the perfused rabbit ear

DEFF Research Database (Denmark)

Bent-Hansen, L; Svendsen, Jesper Hastrup

1991-01-01

The tissue to plasma transfer of 131I-albumin was recorded in perfused rabbit ears (n = 6) following equilibration for 24 hr. 125I-fibrinogen served as the plasma marker, and was introduced intravenously 15 min before clamping. The ears were rollerpump perfused with isotonic diluted plasma...

Muscle irisin response to aerobic vs HIIT in overweight female adolescents.

Science.gov (United States)

Archundia-Herrera, Carolina; Macias-Cervantes, Maciste; Ruiz-Muñoz, Bernardo; Vargas-Ortiz, Katya; Kornhauser, Carlos; Perez-Vazquez, Victoriano

2017-01-01

Exercise stimulates the production of fibronectin type III domain-containing protein 5 (FNDC5), which is cleaved to release a protein called irisin. This protein induces browning of white adipose tissue resulting in increased thermogenesis. Different studies have measured circulating irisin at baseline and in response to exercise among a wide variety of individuals; yet, regarding the effect of different exercise intensities in obese adolescent girls, limited insight is available. This study compares the effect of acute aerobic exercise of moderate intensity and high-intensity interval training (HIIT) on irisin levels in skeletal muscle and plasma of sedentary overweight or obese female adolescents. The aerobic group (n = 15) and HIIT group (n = 15) underwent anthropometric and metabolic measurements, electrocardiogram, peak oxygen uptake (VO 2peak ), and two vastus lateralis muscle biopsies before and after session of workout. The session of aerobic exercise included cycling at 65% of their peak heart rate (HRpeak) for 40 min. In the HIIT group, exercise included six bouts of 1 min at 85-95% HRpeak separated by 1 min of recovery. Irisin levels were evaluated in samples of skeletal muscle (western blot) and plasma (ELISA). The levels of expression of irisin in skeletal muscle increased significantly after a session of HIIT (p HIIT session. No increases in plasma irisin concentration were observed.

Concentrations of danofloxacin 18% solution in plasma, milk and tissues after subcutaneous injection in dairy cows

International Nuclear Information System (INIS)

Mestorino, N.; Marchetti, M.L.; Turic, E.; Pesoa, J.; Errecalde, J.

2009-01-01

Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated. Twenty-one dairy cows received a single subcutaneous administration of 18% mesylate danofloxacin salt (6 mg kg -1 ). Plasma and milk samples were obtained at different times until 48 h. Groups of three animals were sacrificed at different post-administration times and tissue samples (mammary gland, uterus, duodenum, jejunum, ileum, colon and mesenteric lymph nodes) obtained. Danofloxacin concentrations were determined by liquid chromatography with fluorescence detection. The milk WT was calculated by the Time to Safe Concentration method (Software WTM 1.4, EMEA). Danofloxacin was rapidly absorbed and its distribution from plasma to all sampled tissues and milk was extensive. Milk and tissues concentrations were several times above those found in plasma. Plasma area under the curve (AUCp) was 9.69 μg h mL -1 and its elimination half life (T β 1/2 ) was 12.53 h. AUC values for the various tissues and milk greatly exceeded AUCp. T β 1/2 from milk and tissues ranged between 4.57 and 21.91 h and the milk withdrawal time was 73.48 h. The reported results support the potential use of danofloxacin in the treatment of mastitis and other infections in milk cows with 3 days of withdrawal

Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients

Directory of Open Access Journals (Sweden)

Takashi Takeshita

2017-10-01

Full Text Available BACKGROUND: ESR1 mutation in circulating cell-free DNA (cfDNA is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. METHODS: ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC (35 tumor tissue samples and 67 plasma samples. RESULTS: Of the 35 paired samples, 26 (74.3% were concordant: one patient had detectable ESR1 mutations both plasma (ESR1 Y537S/Y537N and tumor tissue (ESR1 Y537S/Y537C, and 25 had WT ESR1 alleles in both. Nine (25.7% had discordance between the plasma and tissue results: five had mutations detected only in their tumor tissue (two Y537S, one Y537C, one D538G, and one Y537S/Y537N/D538G, and four had mutations detected only in their plasma (one Y537S, one Y537N, and two Y537S/Y537N/D538G. Furthermore, longitudinal plasma samples from 19 patients were used to assess changes in the presence of ESR1 mutations during treatment. Eleven patients had cfDNA ESR1 mutations over the course of treatment. A total of eight of 11 patients with MBC with cfDNA ESR1 mutations (72.7% had the polyclonal mutations. CONCLUSION: We have shown the independent distribution of ESR1 mutations between plasma and tumor tissue in 35 patients with MBC.

Novel Mechanism of Plasma Prekallikrein (PK) Activation by Vascular Smooth Muscle Cells: Evidence of the presence of PK Activator

OpenAIRE

Keum, Joo-Seob; Jaffa, Miran A; Luttrell, Louis M; Jaffa, Ayad A.

2014-01-01

The contribution of plasma prekallikrein (PK) to vascular remodeling is becoming increasingly recognized. Plasma PK is activated when the zymogen PK is digested to an active enzyme by activated factor XII (FXII). Here, we present our findings that vascular smooth muscle cells (VSMC) activate plasma PK in the absence of FXII. Extracted plasma membrane and cytosolic fractions of VSMCs activate PK, but the rate of PK activation was greater by the membrane fraction. FXII neutralizing antibody did...

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.

Does a Better Perfusion of Deconditioned Muscle Tissue Release Chronic Low Back Pain?

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Paola Valdivieso

2018-03-01

Full Text Available Non-specific chronic low back pain (nsCLBP is a multifactorial condition of unknown etiology and pathogenesis. Physical and genetic factors may influence the predisposition of individuals to CLBP, which in many instances share a musculoskeletal origin. A reduced pain level in low back pain patients that participate in exercise therapy highlights that disuse-related muscle deconditioning may predispose individuals to nsCLBP. In this context, musculoskeletal pain may be the consequence of capillary rarefaction in inactive muscle as this would lower local tissue drainage and washing out of toxic waste. Muscle activity is translated into an angio-adaptative process, which implicates angiogenic-gene expression and individual response differences due to heritable modifications of such genes (gene polymorphisms. The pathophysiologic mechanism underlying nsCLBP is still largely unaddressed. We hypothesize that capillary rarefaction due to a deconditioning of dorsal muscle groups exacerbates nsCLBP by increasing noxious sensation, reducing muscle strength and fatigue resistance by initiating a downward spiral of local deconditioning of back muscles which diminishes their load-bearing capacity. We address the idea that specific factors such as angiotensin-converting enzyme and Tenascin-C might play an important role in altering susceptibility to nsCLBP via their effects on microvascular perfusion and vascular remodeling of skeletal muscle, inflammation, and pain sensation. The genetic profile may help to explain the individual predisposition to nsCLBP, thus identifying subgroups of patients, which could benefit from ad hoc treatment types. Future therapeutic approaches aimed at relieving the pain associated with nsCLBP should be based on the verification of mechanistic processes of activity-induced angio-adaptation and muscle-perfusion.

A random sampling approach for robust estimation of tissue-to-plasma ratio from extremely sparse data.

Science.gov (United States)

Chu, Hui-May; Ette, Ene I

2005-09-02

his study was performed to develop a new nonparametric approach for the estimation of robust tissue-to-plasma ratio from extremely sparsely sampled paired data (ie, one sample each from plasma and tissue per subject). Tissue-to-plasma ratio was estimated from paired/unpaired experimental data using independent time points approach, area under the curve (AUC) values calculated with the naïve data averaging approach, and AUC values calculated using sampling based approaches (eg, the pseudoprofile-based bootstrap [PpbB] approach and the random sampling approach [our proposed approach]). The random sampling approach involves the use of a 2-phase algorithm. The convergence of the sampling/resampling approaches was investigated, as well as the robustness of the estimates produced by different approaches. To evaluate the latter, new data sets were generated by introducing outlier(s) into the real data set. One to 2 concentration values were inflated by 10% to 40% from their original values to produce the outliers. Tissue-to-plasma ratios computed using the independent time points approach varied between 0 and 50 across time points. The ratio obtained from AUC values acquired using the naive data averaging approach was not associated with any measure of uncertainty or variability. Calculating the ratio without regard to pairing yielded poorer estimates. The random sampling and pseudoprofile-based bootstrap approaches yielded tissue-to-plasma ratios with uncertainty and variability. However, the random sampling approach, because of the 2-phase nature of its algorithm, yielded more robust estimates and required fewer replications. Therefore, a 2-phase random sampling approach is proposed for the robust estimation of tissue-to-plasma ratio from extremely sparsely sampled data.

Tissue protein metabolism in parasitized animals

International Nuclear Information System (INIS)

Symons, L.E.A.; Steel, J.W.; Jones, W.O.

1981-01-01

The effects of gastrointestinal nematode infection of mammals, particularly of the small intestine of the sheep, on protein metabolism of skeletal muscle, liver, the gastrointestinal tract and wool are described. These changes have been integrated to explain poor growth and production in the sheep heavily infected with Trichostrongylus colubriformis. The rates of both synthesis and catabolism of muscle protein are depressed, but nitrogen is lost from this tissue because the depression of synthesis exceeds that of catabolism. Anorexia is the major cause of these changes. Although the effect on liver protein synthesis is unclear, it is probable that the leakage of plasma proteins into the gastrointestinal tract stimulates an early increase in the rate of synthesis of these proteins, but this eventually declines and is insufficient to correct developing hypoalbuminaemia. Changes in the intestinal tract are complex. Exogenous nitrogen is reduced by anorexia, but the flow of nitrogen through the tract from abomasum to faeces is above normal because of the increase of endogenous protein from leakage of plasma protein and, presumably, from exfoliated epithelial cells. There is evidence that protein metabolism of intestinal tissue, particularly in the uninfected distal two-thirds, is increased. Synthesis of wool protein is decreased. As the result of anorexia, intestinal loss of endogenous protein and an increased rate of intestinal protein metabolism there is a net movement of amino nitrogen from muscle, liver and possibly skin to the intestine of the heavily infected sheep. Thus, the availability of amino nitrogen for growth and wool production is reduced. (author)

Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6

DEFF Research Database (Denmark)

Steensberg, A; Van Hall, Gerrit; Osada, T

2000-01-01

1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting skeletal muscle is of such a magnitude that it can account for the IL...... and every hour during the exercise. Leg blood flow was measured in parallel by the ultrasound Doppler technique. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). 3. Arterial plasma concentrations for IL-6 increased 19-fold compared to rest. The a-fv difference for IL-6 over the exercising leg...... followed the same pattern as did the net IL-6 release. Over the resting leg, there was no significant a-fv difference or net IL-6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL-6 production was 6.8 ng min-1 (kg active muscle)-1...

Content of alpha-linolenic acid in human atrial tissue correlates with plasma levels of alpha-linolenic acid

DEFF Research Database (Denmark)

Gu, Jiwei; Eschen, Rikke Bülow; Andreasen, Annette

and ALA levels were compared by the Pearson correlation coefficient. Results: There was a statistical significant correlation (r=0.54, 95% confidence interval: 0.30-0.71) between levels of ALA in plasma phospholipids and atrial tissue. Conclusion: The content of ALA in plasma phospholipids is a short term...... indicator of intake of ALA and this correlated well with the content of ALA in atrial tissue. Atrial tissue is not readily available but this study shows that determination of plasma phospholipids may be useful to further investigate an antiarrhythmic effect of ALA on AF....

Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity.

Science.gov (United States)

M K, Praveen Kumar; Shyama, Soorambail K; D'Costa, Avelyno; Kadam, Samit B; Sonaye, Bhagatsingh Harisingh; Chaubey, Ramesh Chandra

2017-10-01

The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay. Copyright © 2017. Published by Elsevier Inc.

Histomorphological Evaluation of Fresh Ovarian Tissue Transplanted Into Back Muscles of Balb/C Mice

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I Amiri

2011-06-01

Full Text Available & objectives: Today, different methods for maintaining reproductive capability in young women with cancer are being considered. One of the most prominent of these methods is ovarian tissue transplant. Despite the relative success of this method, the appropriate location and methods of transplantation is still a matter of discussion. The present study evaluated the histomorphology of fresh ovarian tissue transplantation by two methods, inter muscular and intra muscular, in Balb/C mice. Methods & Materials: The study was conducted at Hamedan University of Medical Sciences in 2009. Fresh ovarian tissues from 12-14 day old Balb/C mice were transplanted into back muscles of ovarectomized 6 week old Balb/C mice both intermuscularly and intramuscularly. All transplanted mice received intra-peritoneal injections of a unit of rFSH for 4 weeks, every other day. At the end of the tenth week, all transplant recipient mice were killed and the transplanted ovarian tissues were removed. All samples were assessed for the angiogenesis and viability of follicles. Data were analyzed using SPSS software, using independent t- test. Results: In intermuscular transplanted group, the transplanted tissues were rejected in two cases. In the sections prepared from the other cases, in spite of the presence of some small necrotic areas, the majority of ovarian tissues had a healthy appearance within the primordial, primary, secondary and antral follicles. Apart from a significant reduction in the number of follicles and smaller size of follicles in the transplanted tissue in comparison with control group, no other major differences in morphology, histology, and the process of maturation of ovarian follicles were observed between the transplanted and control groups. Conclusion: Fresh ovarian tissue transplantation into muscles of the back area without basic vascular pedicle has new angiogenesis capabilities, appropriate survival and development of primordial follicles and

A review: Functional near infrared spectroscopy evaluation in muscle tissues using Monte Carlo simulation

Science.gov (United States)

Halim, A. A. A.; Laili, M. H.; Salikin, M. S.; Rusop, M.

2018-05-01

Monte Carlo Simulation has advanced their quantification based on number of the photon counting to solve the propagation of light inside the tissues including the absorption, scattering coefficient and act as preliminary study for functional near infrared application. The goal of this paper is to identify the optical properties using Monte Carlo simulation for non-invasive functional near infrared spectroscopy (fNIRS) evaluation of penetration depth in human muscle. This paper will describe the NIRS principle and the basis for its proposed used in Monte Carlo simulation which focused on several important parameters include ATP, ADP and relate with blow flow and oxygen content at certain exercise intensity. This will cover the advantages and limitation of such application upon this simulation. This result may help us to prove that our human muscle is transparent to this near infrared region and could deliver a lot of information regarding to the oxygenation level in human muscle. Thus, this might be useful for non-invasive technique for detecting oxygen status in muscle from living people either athletes or working people and allowing a lots of investigation muscle physiology in future.

Radioimmunoassay of cholecystokinin in human tissue and plasma

International Nuclear Information System (INIS)

Jansen, J.B.M.J.; Lamers, C.B.H.W.

1983-01-01

A highly sensitive radioimmunoassay for cholecystokinin (CCK) without any cross-reactivity with gastrin is described. The antibody was raised in a rabbit by immunisation with 30% CCK and bound to all COOH-terminal CCK-peptides containing at least 14 amino acid residues. The affinity constant of the antibody was 59.4 x 10 10 l/mol. CCK 33 conjugated to [ 125 I]hydroxyphenylpropionic acid-succinimide ester was used as label. The binding between label and antibody was inhibited by 50% (ID 50 ) at a concentration of 2.8 pmol/l cholecystokinin 33. The detection limit of the assay was between 0.5 and 1.0 pmol/l plasma. Concentrations of CCK in aqueous acid extracts of human upper small intestine were 36.5 +- 9.8 pmol/g and of human cerebral cortex 28.2 +- 2.5 pmol/g tissue. Plasma samples were extracted in 96% ethanol prior to assay. No advantage was obtained by adding aprotinin to the tubes. When frozen at -20 0 C plasma CCK was stable for at least 6 months. Basal plasma CCK concentrations in 30 normal subjects were very low, 0.9 +- 0.1 pmol/l, range 0.5 to 3.1 pmol/l. Intraduodenal administration of fat induced significant increases in plasma CCK from 1.1 +- 0.1 to 8.2 +- 1.3 pmol/l (p = 0.01). Infusion of exogenous CCK, resulting in plasma CCK levels slightly lower than those measured during administration of fat, induced pancreatic enzyme secretion and gallbladder contraction. The reliability of this radioimmunoassay for measurements of CCK in human plasma was extensively evaluated. (Auth.)

Muscle force depends on the amount of transversal muscle loading.

Science.gov (United States)

Siebert, Tobias; Till, Olaf; Stutzig, Norman; Günther, Michael; Blickhan, Reinhard

2014-06-03

Skeletal muscles are embedded in an environment of other muscles, connective tissue, and bones, which may transfer transversal forces to the muscle tissue, thereby compressing it. In a recent study we demonstrated that transversal loading of a muscle with 1.3Ncm(-2) reduces maximum isometric force (Fim) and rate of force development by approximately 5% and 25%, respectively. The aim of the present study was to examine the influence of increasing transversal muscle loading on contraction dynamics. Therefore, we performed isometric experiments on rat M. gastrocnemius medialis (n=9) without and with five different transversal loads corresponding to increasing pressures of 1.3Ncm(-2) to 5.3Ncm(-2) at the contact area between muscle and load. Muscle loading was induced by a custom-made plunger which was able to move in transversal direction. Increasing transversal muscle loading resulted in an almost linear decrease in muscle force from 4.8±1.8% to 12.8±2% Fim. Compared to an unloaded isometric contraction, rate of force development decreased from 20.2±4.0% at 1.3Ncm(-2) muscle loading to 34.6±5.7% at 5.3Ncm(-2). Experimental observation of the impact of transversal muscle loading on contraction dynamics may help to better understand muscle tissue properties. Moreover, applying transversal loads to muscles opens a window to analyze three-dimensional muscle force generation. Data presented in this study may be important to develop and validate muscle models which enable simulation of muscle contractions under compression and enlighten the mechanisms behind. Copyright © 2014 Elsevier Ltd. All rights reserved.

Expression of somatostatin receptors subtype 2 and 5 in extraocular muscle tissue of hypothyroidism animal induced by 131I

International Nuclear Information System (INIS)

Li Fangdu; Chu Qiaomei; Xu Peikang; Yao Xiaohong; Shen Jiangfan

2012-01-01

Objective: To observe the expression and distribution of somatostatin receptors 2 and 5 (SSTR2, 5) in extraocular muscle in hypothyroidism and thyroid associated ophthalmopathy (TAO) Wister rats induced by 131 I. Methods: 20 Wister rats were randomly divided into experimental group and normal group(group D). According to 131 I doses of intraperitoneal injection, the experimental groups were divided into low (group A), middle (group B) and high dose group (group C). After 8 weeks, all rats were sacrificed and orbital tissue sections were applied to HE staining and Immunohistochemistry for the analysis of rat orbital tissue changes and SSTR2 and 5 distribution in extraocular muscle. Results: The serum FT 4 levels in group A (16.98±2.92 pmol / L), group B (1.84±0.44 pmol / L) and group C (1.35 ±0.37 pmol /L) eight weeks after 131 I injection were decreased, and had significant difference compared with group D (P 4 levels in group B and C were significantly lower than that in group A (P 0.05). Orbital tissue in experimental group showed mucoid degeneration and edema, the extent was about 25% in group A, 50% in group B, 70% in group C. The rats in group B and group C appeared obvious proliferation of fibrous and adipose tissue, muscle fibers degeneration fracture, even extraocular muscles in group C have vacuole formation. Immunohistochemical analysis displayed highest SSTR5 distribution and strongest expression was in extraocular muscle of group C, second in A B combination group (A and B groups)and weakest in group D. There were significant differences between A B combination group,group C and group D (P 0.05). Conclusion: This study observed the distribution and expression of SSTR2 and SSTR5 in extraocular muscle on the established hypothyroidism animal model. It is some significance for understanding the mechanism of somatostatin receptors in occurrence and development of TAO, similar to provide a reference for the use of somatostatin analogue orbital imaging

Tissue gadolinium deposition in renally impaired rats exposed to different gadolinium-based MRI contrast agents: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

Science.gov (United States)

Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Kanki, Akihiko; Watanabe, Shigeru; Nishimura, Hirotake; Tanimoto, Daigo; Higashi, Hiroki; Yamamoto, Akira

2013-10-01

To quantify tissue gadolinium (Gd) deposition in renally impaired rats exposed to Gd-EOB-DTPA and other Gd-based MRI contrast agents by means of inductively coupled plasma mass spectrometry (ICP-MS), and to compare the differences in distribution among major organs as possible triggers for nephrogenic systemic fibrosis (NSF). A total of 15 renally impaired rats were injected with Gd-EOB-DTPA, Gd-DTPA-BMA and Gd-HP-DO3A. Gd contents of skin, liver, kidney, lung, heart, spleen, diaphragm and femoral muscle were measured by inductively coupled plasma mass spectrometry (ICP-MS). Histological assessment was also conducted. Tissue Gd deposition in all organs was significantly higher (P=0.005~0.009) in the Gd-DTPA-BMA group than in the Gd-HP-DO3A and Gd-EOB-DTPA groups. In the Gd-DTPA-BMA group, Gd was predominantly deposited in kidney (1306±605.7μg/g), followed by skin, liver, lung, spleen, femoral muscle, diaphragm and heart. Comparing Gd-HP-DO3A and Gd-EOB-DTPA groups, Gd depositions in the kidney, liver and lung were significantly lower (P=0.009~0.011) in the Gd-EOB-DTPA group than in the Gd-HP-DO3A group although no significant differences were seen for any other organs. Gd-EOB-DTPA is a stable and safe Gd-based contrast agent (GBCA) showing lower Gd deposition in major organs in renally impaired rats, compared with other GBCAs. This fact suggests that the risk of NSF onset would be low in the use of Gd-EOB-DTPA. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanical characterization of the mouse diaphragm with optical coherence elastography reveals fibrosis-related change of direction-dependent muscle tissue stiffness

Science.gov (United States)

Wang, Shang; Loehr, James A.; Larina, Irina V.; Rodney, George G.; Larin, Kirill V.

2016-03-01

The diaphragm, composed of skeletal muscle, plays an important role in respiration through its dynamic contraction. Genetic and molecular studies of the biomechanics of mouse diaphragm can provide great insights into an improved understanding and potential treatment of the disorders that lead to diaphragm dysfunction (i.e. muscular dystrophy). However, due to the small tissue size, mechanical assessment of mouse diaphragm tissue under its proper physiological conditions has been challenging. Here, we present the application of noncontact optical coherence elastography (OCE) for quantitative elastic characterization of ex vivo mouse diaphragm. Phase-sensitive optical coherence tomography was combined with a focused air-puff system to capture and measure the elastic wave propagation from tissue surface. Experiments were performed on wildtype and dystrophic mouse diaphragm tissues containing different levels of fibrosis. The OCE measurements of elastic wave propagation were conducted along both the longitudinal and transverse axis of the muscle fibers. Cross-correlation of the temporal displacement profiles from different spatial locations was utilized to obtain the propagation time delay, which was used to calculate the wave group velocity and to further quantify the tissue Young's modulus. Prior to and after OCE assessment, peak tetanic force was measured to monitor viability of the tissue during the elasticity measurements. Our experimental results indicate a positive correlation between fibrosis level and tissue stiffness, suggesting this elastic-wave-based OCE method could be a useful tool to monitor mechanical properties of skeletal muscle under physiological and pathological conditions.

Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear Cells and Platelet-Rich Plasma

OpenAIRE

Seffer, Istvan; Nemeth, Zoltan

2017-01-01

Summary: Peripheral blood mononuclear cells (PBMCs) are multipotent, and plasma contains growth factors involving tissue regeneration. We hypothesized that transplantation of PBMC-plasma will promote the recovery of paralyzed facial muscles in Bell palsy. This case report describes the effects of PBMC-plasma transplantations in a 27-year-old female patient with right side Bell palsy. On the affected side of the face, the treatment resulted in both morphological and functional recovery includi...

Exposure to internal muscle tissue loads under the ischial tuberosities during sitting is elevated at abnormally high or low body mass indices.

Science.gov (United States)

Sopher, Ran; Nixon, Jane; Gorecki, Claudia; Gefen, Amit

2010-01-19

Deep tissue injury (DTI) is a severe pressure ulcer characteristic of chairfast or bedfast individuals, such as those with impaired mobility or neurological disorders. A DTI differs from superficial pressure ulcers in that the onset of DTI occurs under intact skin, in skeletal muscle tissue overlying bony prominences, and progression of the wound continues subcutaneously until skin breakdown. Due to the nature of this silently progressing wound, it is highly important to screen potentially susceptible individuals for their risk of developing a DTI. Abnormally low and high values of the body mass index (BMI) have been proposed to be associated with pressure ulcers, but a clear mechanism is lacking. We hypothesize that during sitting, exposure to internal muscle tissue loads under the ischial tuberosities (IT) is elevated at abnormally high or low body mass indices. Our aims in this study were: (a) to develop biomechanical models of the IT region in the buttocks that represent an individual who is gaining or losing weight drastically. (b) To determine changes in internal tissue load measures: principal compression strain, strain energy density (SED), principal compression stress and von Mises stress versus the BMI. (c) To determine percentage volumes of muscle tissue exposed to critical levels of the above load measures, which were defined based on our previous animal and tissue engineered model experiments: strain>or=50%, stress>or=2 kPa, SED>or=0.5 kPa. A set of 21 finite element models, which represented the same individual, but with different BMI values within the normal range, above it and below it, was solved for the outcome measures listed above. The models had the same IT shape, size, distance between the IT, and (non-linear) mechanical properties for all soft tissues, but different thicknesses of gluteus muscles and fat tissue layers, corresponding to the BMI level. The resulted data indicated a trend of progressive increase in internal tissue loading

In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices.

Science.gov (United States)

Lu, Helen H; Kofron, Michelle D; El-Amin, Saadiq F; Attawia, Mohammed A; Laurencin, Cato T

2003-06-13

Over 800,000 bone grafting procedures are performed in the United States annually, creating a demand for viable alternatives to autogenous bone, the grafting standard in osseous repair. The objective of this study was to examine the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype and in vitro bone formation by muscle-derived cells. Specifically, we evaluated the ability of bone morphogenetic protein-7 (BMP-7), delivered from a poly(lactide-co-glycolide) (PLAGA) matrix, to induce the differentiation of cells derived from rabbit skeletal muscle into osteoblast-like cells and subsequently form mineralized tissue. Results confirmed that muscle-derived cells attached and proliferated on the PLAGA substrates. BMP-7 released from PLAGA induced the muscle-derived cells to increase bone marker expression and form mineralized cultures. These results demonstrate the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype by muscle-derived cells and present a new paradigm for bone tissue engineering.

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport

International Nuclear Information System (INIS)

Rebouche, C.J.; Engel, A.G.

1984-01-01

The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and ''other tissues'') was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract

Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.

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Cristina Herrera

2016-04-01

Full Text Available The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM and other extracellular matrix (ECM proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

Short-term immobilization and recovery affect skeletal muscle but not collagen tissue turnover in humans

DEFF Research Database (Denmark)

Christensen, Britt; Dyrberg, Eva; Aagaard, Per

2008-01-01

Not much is known about the effects of immobilization and subsequent recovery on tendon connective tissue. In the present study, healthy young men had their nondominant leg immobilized for a 2-wk period, followed by a recovery period of the same length. Immobilization resulted in a mean decrease...... of 6% (5,413 to 5,077 mm(2)) in cross-sectional area (CSA) of the triceps surae muscles and a mean decrease of 9% (261 to 238 N.m) in strength of the immobilized calf muscles. Two weeks of recovery resulted in a 6% increased in CSA (to 5,367 mm(2)), whereas strength remained suppressed (240 N...... muscle size and strength, while tendon size and collagen turnover were unchanged. While recovery resulted in an increase in muscle size, strength was unchanged. No significant difference in tendon size could be detected between the two legs after 2 wk of recovery, although collagen synthesis...

Matrilin-2, an extracellular adaptor protein, is needed for the regeneration of muscle, nerve and other tissues

Directory of Open Access Journals (Sweden)

Éva Korpos

2015-01-01

Full Text Available The extracellular matrix (ECM performs essential functions in the differentiation, maintenance and remodeling of tissues during development and regeneration, and it undergoes dynamic changes during remodeling concomitant to alterations in the cell-ECM interactions. Here we discuss recent data addressing the critical role of the widely expressed ECM protein, matrilin-2 (Matn2 in the timely onset of differentiation and regeneration processes in myogenic, neural and other tissues and in tumorigenesis. As a multiadhesion adaptor protein, it interacts with other ECM proteins and integrins. Matn2 promotes neurite outgrowth, Schwann cell migration, neuromuscular junction formation, skeletal muscle and liver regeneration and skin wound healing. Matn2 deposition by myoblasts is crucial for the timely induction of the global switch toward terminal myogenic differentiation during muscle regeneration by affecting transforming growth factor beta/bone morphogenetic protein 7/Smad and other signal transduction pathways. Depending on the type of tissue and the pathomechanism, Matn2 can also promote or suppress tumor growth.

An examination of the elastic properties of tissue-mimicking phantoms using vibro-acoustography and a muscle motor system

Science.gov (United States)

Maccabi, A.; Taylor, Z.; Bajwa, N.; Mallen-St. Clair, J.; St. John, M.; Sung, S.; Grundfest, W.; Saddik, G.

2016-02-01

Tissue hardness, often quantified in terms of elasticity, is an important differentiating criterion for pathological identity and is extensively used by surgeons for tumor localization. Delineation of malignant regions from benign regions is typically performed by visual inspection and palpation. Although practical, this method is highly subjective and does not provide quantitative metrics. We have previously reported on Vibro-Acoustography (VA) for tumor delineation. VA is unique in that it uses the specific, non-linear properties of tumor tissue in response to an amplitude modulated ultrasound beam to generate spatially resolved, high contrast maps of tissue. Although the lateral and axial resolutions (sub-millimeter and sub-centimeter, respectively) of VA have been extensively characterized, the relationship between static stiffness assessment (palpation) and dynamic stiffness characterization (VA) has not been explicitly established. Here we perform a correlative exploration of the static and dynamic properties of tissue-mimicking phantoms, specifically elasticity, using VA and a muscle motor system. Muscle motor systems, commonly used to probe the mechanical properties of materials, provide absolute, quantitative point measurements of the elastic modulus, analogous to Young's modulus, of a target. For phantoms of varying percent-by-weight concentrations, parallel VA and muscle motor studies conducted on 18 phantoms reveal a negative correlation (p < - 0.85) between mean signal amplitude levels observed with VA and calculated elastic modulus values from force vs. indentation depth curves. Comparison of these elasticity measurements may provide additional information to improve tissue modeling, system characterization, as well as offer valuable insights for in vivo applications, specifically surgical extirpation of tumors.

Assessment of the biological variation of plasma tissue inhibitor of metalloproteinases-1

DEFF Research Database (Denmark)

Frederiksen, C.B.; Lomholt, Anne Fog; Lottenburger, Tine

2008-01-01

BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) measurements in plasma may be useful for the early detection and prognosis of colorectal cancer (CRC). Data on analytical performance and normal intra- and interindividual biological variation are required in order to interpret...... the utility of TIMP-1 in CRC. The aim of this study was to establish the biological and analytical variation of plasma TIMP-1 in volunteers. MATERIAL AND METHODS: Three separate studies were undertaken. 1: Plasma was collected from 23 volunteers 6 times within a 3-week period, first in September 2004 (round...

The Influence of Dietary Habits and Meat Consumption on Plasma 3‐Methylhistidine—A Potential Marker for Muscle Protein Turnover

Science.gov (United States)

Kochlik, Bastian; Gerbracht, Christiana; Grune, Tilman

2018-01-01

Scope 3‐Methylhistidine (3‐MH) as a potential biomarker for muscle protein turnover is influenced by meat intake but data on the impact of meat on plasma 3‐MH are scarce. We determined the association of plasma 3‐MH, 1‐methylhistidine (1‐MH), and creatinine with dietary habits and assessed the impact of a single white meat intervention during a meat‐free period. Methods and results Plasma 3‐MH, 1‐MH, and creatinine concentrations of healthy young omnivores (n = 19) and vegetarians (n = 16) were analyzed together with data on anthropometry, body composition, grip strength, and nutrition. After baseline measurements omnivores adhered to a meat‐free diet for 6 days and received a defined administration of chicken breast on day four. At baseline, omnivores had higher plasma 3‐MH and 1‐MH concentrations than vegetarians. White meat administration led to a slight increase in plasma 3‐MH in omnivores. The elevated 3‐MH concentrations significantly declined within 24 h after white meat intake. Conclusion 1‐MH concentrations in plasma seem to be suitable to display (white) meat consumption and its influence on 3‐MH plasma concentration. 3‐MH in plasma may be used as a biomarker for muscle protein turnover if subjects have not consumed meat in the previous 24 h. PMID:29573154

Immunology Guides Skeletal Muscle Regeneration

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F. Andrea Sass

2018-03-01

Full Text Available Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

Science.gov (United States)

Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

2016-07-01

We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.

Design, fabrication and characterization of oxidized alginate-gelatin hydrogels for muscle tissue engineering applications.

Science.gov (United States)

Baniasadi, Hossein; Mashayekhan, Shohreh; Fadaoddini, Samira; Haghirsharifzamini, Yasamin

2016-07-01

In this study, we reported the preparation of self cross-linked oxidized alginate-gelatin hydrogels for muscle tissue engineering. The effect of oxidation degree (OD) and oxidized alginate/gelatin (OA/GEL) weight ratio were examined and the results showed that in the constant OA/GEL weight ratio, both cross-linking density and Young's modulus enhanced by increasing OD due to increment of aldehyde groups. Furthermore, the degradation rate was increased with increasing OD probably due to decrement in alginate molecular weight during oxidation reaction facilitated degradation of alginate chains. MTT cytotoxicity assays performed on Wharton's Jelly-derived umbilical cord mesenchymal stem cells cultured on hydrogels with OD of 30% showed that the highest rate of cell proliferation belong to hydrogel with OA/GEL weight ratio of 30/70. Overall, it can be concluded from all obtained results that the prepared hydrogel with OA/GEL weight ratio and OD of 30/70 and 30%, respectively, could be proper candidate for use in muscle tissue engineering. © The Author(s) 2016.

Final Report for completed IPP Project:"Development of Plasma Ablation for Soft Tissue and Bone Surgery"

Energy Technology Data Exchange (ETDEWEB)

Brown, Ian

2009-09-01

ArthroCare is a medical device company that develops, manufactures, and markets an advanced surgical tool, a plasma electro-surgical system for cutting and removing tissue. The hand-held electrical discharge device produces plasma in a biocompatible conductive fluid and tissue to which it is applied during surgery. Its products allow surgeons to operate with increased precision and accuracy, limiting damage to surrounding tissue thereby reducing pain and speeding recovery for the patient. In the past, the design of ArthfoCare's plasma wands has been an empirical undertaking. One goal of this R&D program was to put the phenomena involved on a sound scientific footing, allowing optimization of existing plasma based electro-surgery system technology, and the design and manufacture of new and improved kinds of scalpels, in particular for the surgical cutting of bone. Another important related goal of the program was to develop, through an experimental approach, new plasma wand approaches to the cutting ('shaving') of hard bone tissue. The goals of the CRADA were accomplished - computer models were used to predict important parameters of the plasma discharge and the bone environment, and several different approaches to bone-shaving were developed and demonstrated. The primary goal of the project was to develop and demonstrate an atmospheric-pressure plasma tool that is suitable for surgical use for shaving bone in humans. This goal was accomplished, in fact with several different alternative plasma approaches. High bone ablation speeds were measured. The use of probes ('plasma wand' - the surgical tool) with moving active electrodes was also explored, and there are advantages to this method. Another important feature is that the newly-exposed bone surface have only a very thin necrosis layer; this feature was demonstrated. This CRADA has greatly advanced our understanding of bone removal by atmospheric pressure plasmas in liquid, and puts Arthro

Final Report for completed IPP Project: Development of Plasma Ablation for Soft Tissue and Bone Surgery

International Nuclear Information System (INIS)

Brown, Ian

2009-01-01

ArthroCare is a medical device company that develops, manufactures, and markets an advanced surgical tool, a plasma electro-surgical system for cutting and removing tissue. The hand-held electrical discharge device produces plasma in a biocompatible conductive fluid and tissue to which it is applied during surgery. Its products allow surgeons to operate with increased precision and accuracy, limiting damage to surrounding tissue thereby reducing pain and speeding recovery for the patient. In the past, the design of ArthfoCare's plasma wands has been an empirical undertaking. One goal of this R and D program was to put the phenomena involved on a sound scientific footing, allowing optimization of existing plasma based electro-surgery system technology, and the design and manufacture of new and improved kinds of scalpels, in particular for the surgical cutting of bone. Another important related goal of the program was to develop, through an experimental approach, new plasma wand approaches to the cutting ('shaving') of hard bone tissue. The goals of the CRADA were accomplished - computer models were used to predict important parameters of the plasma discharge and the bone environment, and several different approaches to bone-shaving were developed and demonstrated. The primary goal of the project was to develop and demonstrate an atmospheric-pressure plasma tool that is suitable for surgical use for shaving bone in humans. This goal was accomplished, in fact with several different alternative plasma approaches. High bone ablation speeds were measured. The use of probes ('plasma wand' - the surgical tool) with moving active electrodes was also explored, and there are advantages to this method. Another important feature is that the newly-exposed bone surface have only a very thin necrosis layer; this feature was demonstrated. This CRADA has greatly advanced our understanding of bone removal by atmospheric pressure plasmas in liquid, and puts ArthroCare in a good

Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

Science.gov (United States)

Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C; Dedmon, William L; Katsanos, Christos S

2016-10-01

Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA. Copyright © 2016 the American Physiological Society.

CD36-dependent Regulation of Muscle FoxO1 and PDK4 in the PPARδ/β-mediated Adaptation to Metabolic Stress*

OpenAIRE

Nahlé, Zaher; Hsieh, Michael; Pietka, Terri; Coburn, Chris T.; Grimaldi, Paul A.; Zhang, Michael Q.; Das, Debopriya; Abumrad, Nada A.

2008-01-01

The transcription factor FoxO1 contributes to the metabolic adaptation to fasting by suppressing muscle oxidation of glucose, sparing it for glucose-dependent tissues. Previously, we reported that FoxO1 activation in C2C12 muscle cells recruits the fatty acid translocase CD36 to the plasma membrane and increases fatty acid uptake and oxidation. This, together with FoxO1 induction of lipoprotein lipase, would promote the reliance on fatty acid utilization characteristic of the fasted muscle. H...

Effect of eccentric exercise with reduced muscle glycogen on plasma interleukin-6 and neuromuscular responses of musculus quadriceps femoris.

Science.gov (United States)

Gavin, James P; Myers, Stephen D; Willems, Mark E T

2016-07-01

Eccentric exercise can result in muscle damage and interleukin-6 (IL-6) secretion. Glycogen availability is a potent stimulator of IL-6 secretion. We examined effects of eccentric exercise in a low-glycogen state on neuromuscular function and plasma IL-6 secretion. Twelve active men (23 ± 4 yr, 179 ± 5 cm, 77 ± 10 kg, means ± SD) completed two downhill treadmill runs (gradient, -12%, 5 × 8 min; speed, 12.1 ± 1.1 km/h) with normal (NG) and reduced muscle glycogen (RG) in randomized order and at least 6 wk apart. Muscle glycogen was reduced using an established cycling protocol until exhaustion and dietary manipulation the evening before the morning run. Physiological responses were measured up to 48 h after the downhill runs. During recovery, force deficits of musculus quadriceps femoris by maximal isometric contractions were similar. Changes in low-frequency fatigue were larger with RG. Voluntary activation and plasma IL-6 levels were similar in recovery between conditions. It is concluded that unaccustomed, damaging eccentric exercise with low muscle glycogen of the m. quadriceps femoris 1) exacerbated low-frequency fatigue but 2) had no additional effect on IL-6 secretion. Neuromuscular impairment after eccentric exercise with low muscle glycogen appears to have a greater peripheral component in early recovery. Copyright © 2016 the American Physiological Society.

An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo.

Directory of Open Access Journals (Sweden)

Cameron B Williams

Full Text Available The current study tested the hypothesis that a single, moderate dose of RSV would activate the AMPK/SIRT1 axis in human skeletal muscle and adipose tissue. Additionally, the effects of RSV on mitochondrial respiration in PmFBs were examined. Eight sedentary men (23.8±2.4 yrs; BMI: 32.7±7.1 reported to the lab on two occasions where they were provided a meal supplemented with 300 mg of RSV or a placebo. Blood samples, and a muscle biopsy were obtained in the fasted state and again, with the addition of an adipose tissue biopsy, two hours post-prandial. The effect of RSV on mitochondrial respiration was examined in PmFBs taken from muscle biopsies from an additional eight men (23.4±5.4 yrs; BMI: 24.4±2.8. No effect of RSV was observed on nuclear SIRT1 activity, acetylation of p53, or phosphorylation of AMPK, ACC or PKA in either skeletal muscle or adipose tissue. A decrease in post absorptive insulin levels was accompanied by elevated skeletal muscle phosphorylation of p38 MAPK, but no change in either skeletal muscle or adipose tissue insulin signalling. Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100-300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production.

Effect of tissue and plasma factors on kidney proliferation.

Science.gov (United States)

Inda, A M; García, A L; Errecalde, A L; Badrán, A F

1997-04-01

Liver extract, plasma from intact mice, ES2 tumour extract and plasma from tumour bearing mice has an inhibiting effect on the mitotic activity of hepatocytes and duodenal enterocytes. In the present experiments, the effect of these treatments on the mitotic activity of renal tubular cells was studied. C3HS 28 day-old male mice, standardized for periodicity analysis were used. The determination of normal mitotic circadian curve of the renocytes was done. A second batch of mice were injected with 0.01 ml/gr of either liver extract, plasma from intact mice, ES2 tumour extract or plasma from tumour bearing mice, at 16:00 hours and controlled at 08:00, 12:00 and 16:00 hs during 2 consecutive days post treatment. Colchicine (2 micrograms/gr) was injected 4 hours before killing. Kidneys were processed for histology and mitotic index determinations. Results were expressed as colchicine metaphases per 1000 nuclei, and showed that mitotic activity values of treated animals were significantly lower than those of controls. In conclusion, mitotic activity inhibition of renocytes may be due to some non specific plasmatic and/or tissue factors.

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

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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

The Use of Platelet-Rich and Platelet-Poor Plasma to Enhance Differentiation of Skeletal Myoblasts: Implications for the Use of Autologous Blood Products for Muscle Regeneration.

Science.gov (United States)

Miroshnychenko, Olga; Chang, Wen-Teh; Dragoo, Jason L

2017-03-01

Platelet-rich plasma (PRP) has been used to augment tissue repair and regeneration after musculoskeletal injury. However, there is increasing clinical evidence that PRP does not show a consistent clinical effect. Purpose/Hypothesis: This study aimed to compare the effects of the following non-neutrophil-containing (leukocyte-poor) plasma fractions on human skeletal muscle myoblast (HSMM) differentiation: (1) PRP, (2) modified PRP (Mod-PRP), in which transforming growth factor β1 (TGF-β1) and myostatin (MSTN) were depleted, and (3) platelet-poor plasma (PPP). The hypothesis was that leukocyte-poor PRP would lead to myoblast proliferation (not differentiation), whereas certain modifications of PRP preparations would increase myoblast differentiation, which is necessary for skeletal muscle regeneration. Controlled laboratory study. Blood from 7 human donors was individually processed to simultaneously create leukocyte-poor fractions: PRP, Mod-PRP, PPP, and secondarily spun PRP and Mod-PRP (PRP ss and Mod-PRP ss , respectively). Mod-PRP was produced by removing TGF-β1 and MSTN from PRP using antibodies attached to sterile beads, while a second-stage centrifugal spin of PRP was performed to remove platelets. The biologics were individually added to cell culture groups. Analysis for induction into myoblast differentiation pathways included Western blot analysis, reverse-transcription polymerase chain reaction, and immunohistochemistry, as well as confocal microscopy to assess polynucleated myotubule formation. HSMMs cultured with PRP showed an increase in proliferation but no evidence of differentiation. Western blot analysis confirmed that MSTN and TGF-β1 could be decreased in Mod-PRP using antibody-coated beads, but this modification mildly improved myoblast differentiation. However, cell culture with PPP, PRP ss , and Mod-PRP ss led to a decreased proliferation rate but a significant induction of myoblast differentiation verified by increased multinucleated

MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes.

Science.gov (United States)

Bastiani, Michele; Liu, Libin; Hill, Michelle M; Jedrychowski, Mark P; Nixon, Susan J; Lo, Harriet P; Abankwa, Daniel; Luetterforst, Robert; Fernandez-Rojo, Manuel; Breen, Michael R; Gygi, Steven P; Vinten, Jorgen; Walser, Piers J; North, Kathryn N; Hancock, John F; Pilch, Paul F; Parton, Robert G

2009-06-29

Polymerase I and transcript release factor (PTRF)/Cavin is a cytoplasmic protein whose expression is obligatory for caveola formation. Using biochemistry and fluorescence resonance energy transfer-based approaches, we now show that a family of related proteins, PTRF/Cavin-1, serum deprivation response (SDR)/Cavin-2, SDR-related gene product that binds to C kinase (SRBC)/Cavin-3, and muscle-restricted coiled-coil protein (MURC)/Cavin-4, forms a multiprotein complex that associates with caveolae. This complex can constitutively assemble in the cytosol and associate with caveolin at plasma membrane caveolae. Cavin-1, but not other cavins, can induce caveola formation in a heterologous system and is required for the recruitment of the cavin complex to caveolae. The tissue-restricted expression of cavins suggests that caveolae may perform tissue-specific functions regulated by the composition of the cavin complex. Cavin-4 is expressed predominantly in muscle, and its distribution is perturbed in human muscle disease associated with Caveolin-3 dysfunction, identifying Cavin-4 as a novel muscle disease candidate caveolar protein.

Atmospheric pressure plasma jets interacting with liquid covered tissue: touching and not-touching the liquid

International Nuclear Information System (INIS)

Norberg, Seth A; Johnsen, Eric; Tian, Wei; Kushner, Mark J

2014-01-01

In the use of atmospheric pressure plasma jets in biological applications, the plasma-produced charged and neutral species in the plume of the jet often interact with a thin layer of liquid covering the tissue being treated. The plasma-produced reactivity must then penetrate through the liquid layer to reach the tissue. In this computational investigation, a plasma jet created by a single discharge pulse at three different voltages was directed onto a 200 µm water layer covering tissue followed by a 10 s afterglow. The magnitude of the voltage and its pulse length determined if the ionization wave producing the plasma plume reached the surface of the liquid. When the ionization wave touches the surface, significantly more charged species were created in the water layer with H 3 O + aq , O 3 − aq , and O 2 − aq being the dominant terminal species. More aqueous OH aq , H 2 O 2aq , and O 3aq were also formed when the plasma plume touches the surface. The single pulse examined here corresponds to a low repetition rate plasma jet where reactive species would be blown out of the volume between pulses and there is not recirculation of flow or turbulence. For these conditions, N x O y species do not accumulate in the volume. As a result, aqueous nitrites, nitrates, and peroxynitrite, and the HNO 3aq and HOONO aq , which trace their origin to solvated N x O y , have low densities. (paper)

Resistin in Dairy Cows: Plasma Concentrations during Early Lactation, Expression and Potential Role in Adipose Tissue

Science.gov (United States)

Reverchon, Maxime; Ramé, Christelle; Cognié, Juliette; Briant, Eric; Elis, Sébastien; Guillaume, Daniel; Dupont, Joëlle

2014-01-01

Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA) levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. PMID:24675707

Resistin in dairy cows: plasma concentrations during early lactation, expression and potential role in adipose tissue.

Directory of Open Access Journals (Sweden)

Maxime Reverchon

Full Text Available Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP and at five months of gestation (5 MG. We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6 in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase and HSL (hormone-sensitive lipase in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro.

Enhanced adherence of mouse fibroblast and vascular cells to plasma modified polyethylene

Energy Technology Data Exchange (ETDEWEB)

Reznickova, Alena, E-mail: alena.reznickova@vscht.cz [Department of Solid State Engineering, Institute of Chemical Technology Prague, 166 28 Prague 6 (Czech Republic); Novotna, Zdenka, E-mail: zdenka1.novotna@vscht.cz [Department of Solid State Engineering, Institute of Chemical Technology Prague, 166 28 Prague 6 (Czech Republic); Kolska, Zdenka [Faculty of Science, J.E. Purkyně University, 400 96 Usti nad Labem (Czech Republic); Kasalkova, Nikola Slepickova [Department of Solid State Engineering, Institute of Chemical Technology Prague, 166 28 Prague 6 (Czech Republic); Rimpelova, Silvie [Department of Biochemistry and Microbiology, Institute of Chemical Technology Prague, 166 28 Prague 6 (Czech Republic); Svorcik, Vaclav [Department of Solid State Engineering, Institute of Chemical Technology Prague, 166 28 Prague 6 (Czech Republic)

2015-07-01

Since the last decade, tissue engineering has shown a sensational promise in providing more viable alternatives to surgical procedures for harvested tissues, implants and prostheses. Biomedical polymers, such as low-density polyethylene (LDPE), high-density polyethylene (HDPE) and ultra-high molecular weight polyethylene (UHMWPE), were activated by Ar plasma discharge. Degradation of polymer chains was examined by determination of the thickness of ablated layer. The amount of an ablated polymer layer was measured by gravimetry. Contact angle, measured by goniometry, was studied as a function of plasma exposure and post-exposure aging times. Chemical structure of modified polymers was characterized by angle resolved X-ray photoelectron spectroscopy. Surface chemistry and polarity of the samples were investigated by electrokinetic analysis. Changes in surface morphology were followed using atomic force microscopy. Cytocompatibility of plasma activated polyethylene foils was studied using two distinct model cell lines; VSMCs (vascular smooth muscle cells) as a model for vascular graft testing and connective tissue cells L929 (mouse fibroblasts) approved for standardized material cytotoxicity testing. Specifically, the cell number, morphology, and metabolic activity of the adhered and proliferated cells on the polyethylene matrices were studied in vitro. It was found that the plasma treatment caused ablation of the polymers, resulting in dramatic changes in their surface morphology and roughness. ARXPS and electrokinetic measurements revealed oxidation of the polymer surface. It was found that plasma activation has a positive effect on the adhesion and proliferation of VSMCs and L929 cells. - Highlights: • Plasma activation of LDPE, HDPE and UHMWPE • Study of surface properties by several techniques: ARXPS, AFM, zeta-potential, and goniometry • Investigation of adhesion and spreading of vascular smooth muscle cells (VSMCs) and mouse fibroblasts (L929)

Oscillation of tissue oxygen index in non-exercising muscle during exercise.

Science.gov (United States)

Yano, T; Afroundeh, R; Shirakawa, K; Lian, C-S; Shibata, K; Xiao, Z; Yunoki, T

2015-09-01

The purpose of the present study was to examine how oscillation of tissue oxygen index (TOI) in non-exercising exercise is affected during high-intensity and low-intensity exercises. Three exercises were performed with exercise intensities of 30% and 70% peak oxygen uptake (Vo(2)peak) for 12 min and with exercise intensity of 70% Vo(2)peak for 30 s. TOI in non-exercising muscle (biceps brachii) during the exercises for 12 min was determined by nearinfrared spectroscopy. TOI in the non-exercising muscle during the exercises was analyzed by fast Fourier transform (FFT) to obtain power spectra density (PSD). The frequency at which maximal PSD appeared (Fmax) during the exercise with 70% Vo(2)peak for 12 min (0.00477 ± 0.00172 Hz) was significantly lower than that during the exercise with 30% Vo2peak for 12 min (0.00781 ± 0.00338 Hz). There were significant differences in blood pH and blood lactate between the exercise with 70% Vo(2)peak and the exercise with 30% Vo(2)peak. It is concluded that TOI in nonexercising muscle oscillates during low-intensity exercise as well as during high-intensity exercise and that the difference in Fmax between the two exercises is associated with the difference in increase in blood lactate derived from the exercise.

Tissue

Directory of Open Access Journals (Sweden)

David Morrissey

2012-01-01

Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

Spatial interaction between tissue pressure and skeletal muscle perfusion during contraction.

Science.gov (United States)

van Donkelaar, C C; Huyghe, J M; Vankan, W J; Drost, M R

2001-05-01

The vascular waterfall theory attributes decreased muscle perfusion during contraction to increased intramuscular pressure (P(IM)) and concomitant increase in venous resistance. Although P(IM) is distributed during contractions, this theory does not account for heterogeneity. This study hypothesises that pressure heterogeneity could affect the interaction between P(IM) rise and perfusion. Regional tissue perfusion during submaximum (100kPa) tetanic contraction is studied, using a finite element model of perfused contracting skeletal muscle. Capillary flow in muscles with one proximal artery and vein (SIM(1)) and with an additional distal artery and vein (SIM(2)) is compared. Blood flow and pressures at rest and P(IM) during contraction ( approximately 25kPa maximally) are similar between simulations, but capillary flow and venous pressure differ. In SIM(2), venous pressure and capillary flow correspond to P(IM) distribution, whereas capillary flow in SIM(1) is less than 10% of flow in SIM(2), in the muscle half without draining vein. This difference is caused by a high central P(IM), followed by central venous pressure rise, in agreement with the waterfall theory. The high central pressure (SIM(1)), obstructs outflow from the distal veins. Distal venous pressure rises until central blood pressure is reached, although local P(IM) is low. Adding a distal vein (SIM(2)) restores the perfusion. It is concluded that regional effects contribute to the interaction between P(IM) and perfusion during contraction. Unlike stated by the vascular waterfall theory, venous pressure may locally exceed P(IM). Although this can be explained by the principles of this theory, the theory does not include this phenomenon as such.

Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies

NARCIS (Netherlands)

Klumpers, Ursula M. H.; Veltman, Dick J.; Boellaard, Ronald; Comans, Emile F.; Zuketto, Cassandra; Yaqub, Maqsood; Mourik, Jurgen E. M.; Lubberink, Mark; Hoogendijk, Witte J. G.; Lammertsma, Adriaan A.

2008-01-01

A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been

A Standardized Rat Model of Volumetric Muscle Loss Injury for the Development of Tissue Engineering Therapies

Science.gov (United States)

2012-12-01

appropriate sample size and dura- tion required to adequately characterize a treatment. Further compounding the need for a standard preclinical VML...al. In vivo tissue engineer- ing of functional skeletal muscle by freshly isolated satellite cells embedded in a photopolymerizable hydrogel. FASEB J

Roentgenmorphological muscle changes in anterior horn cell lesions

International Nuclear Information System (INIS)

Palvoelgyi, R.

1979-01-01

The author examined muscles in the extremities of 42 poliomyelitis patients using a special roentgenological technique. This method made it possible to objectively determine the size of the muscles in the soft tissues of the extremities. The volume and distribution of the increased amounts of fatty tissue in the muscle and the volume of normal muscle tissue led to draw conclusions regarding the histological state of the muscle. Roentgenomorphological changes are closely linked to muscle dysfunction. Roentgenological examination of the soft tissue provides a useful supplement to a muscle biopsy and to electromyographic examinations and is of value for the rehabilitation of the patients. (orig.) [de

ADIPONECTIN AND C-REACTIVE PROTEIN RELATIONSHIP IN PLASMA AND ADIPOSE TISSUE (STUDY AMONG HEALTHY OBESE EGYPTIAN FEMALES)

International Nuclear Information System (INIS)

SOLIMAN, S.E.T.

2008-01-01

The adipokine, adiponectin inhibits vascular inflammation and acts as an endogenous modulator of obesity - linked diseases. High - sensitive C-reactive protein (hs-CRP) is recently debated as a risk factor and mediator for atherosclerosis. The present study investigated the association between adiponectin and hs-CRP in plasma and adipose tissue, and their relation to body composition and insulin sensitivity in a cohort of normal (30 subjects), obese (30 subjects) and morbidly - obese females (10 subjects). Messenger RNA (mRNA) expression of CRP and adiponectin in human adipose tissue were measured using real-time polymerase chain reaction. Plasma adiponectin and insulin were measured using radioimmunoassay methods, while, plasma hs-CRP was measured using ultrasensitive latex method.Results showed that adiponectin was negatively correlated with weight, BMI and insulin sensitivity index, and positively correlated with HDLc. The plasma hs-CRP levels were negatively correlated with plasma adiponectin. The plasma adiponectin levels being significantly lower and plasma hs-CRP being significantly higher in obese than normal females. Real- Time PCR analysis revealed the expression of CRP m-RNA in human adipose tissue and this was inversely correlated to adiponectin m RNA. These results suggest that elevation of CRP and reduction of adiponectin could emerge as mediators of atherogenesis and insulin resistance

Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells.

Science.gov (United States)

Hjorth, M; Pourteymour, S; Görgens, S W; Langleite, T M; Lee, S; Holen, T; Gulseth, H L; Birkeland, K I; Jensen, J; Drevon, C A; Norheim, F

2016-05-01

Some health benefits of exercise may be explained by an altered secretion of myokines. Because previous focus has been on upregulated myokines, we screened for downregulated myokines and identified myostatin. We studied the expression of myostatin in relation to exercise and dysglycaemia in skeletal muscle, adipose tissue and plasma. We further examined some effects of myostatin on energy metabolism in primary human muscle cells and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Sedentary men with or without dysglycaemia underwent a 45-min acute bicycle test before and after 12 weeks of combined endurance and strength training. Blood samples and biopsies from m. vastus lateralis and adipose tissue were collected. Myostatin mRNA expression was reduced in skeletal muscle after acute as well as long-term exercise and was even further downregulated by acute exercise on top of 12-week training. Furthermore, the expression of myostatin at baseline correlated negatively with insulin sensitivity. Myostatin expression in the adipose tissue increased after 12 weeks of training and correlated positively with insulin sensitivity markers. In cultured muscle cells but not in SGBS cells, myostatin promoted an insulin-independent increase in glucose uptake. Furthermore, muscle cells incubated with myostatin had an enhanced rate of glucose oxidation and lactate production. Myostatin was differentially expressed in the muscle and adipose tissue in relation to physical activity and dysglycaemia. Recombinant myostatin increased the consumption of glucose in human skeletal muscle cells, suggesting a complex regulatory role of myostatin in skeletal muscle homeostasis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Unusual metabolic characteristics in skeletal muscles of transgenic rabbits for human lipoprotein lipase

Directory of Open Access Journals (Sweden)

Viglietta Céline

2004-12-01

Full Text Available Abstract Background The lipoprotein lipase (LPL hydrolyses circulating triacylglycerol-rich lipoproteins. Thereby, LPL acts as a metabolic gate-keeper for fatty acids partitioning between adipose tissue for storage and skeletal muscle primarily for energy use. Transgenic mice that markedly over-express LPL exclusively in muscle, show increases not only in LPL activity, but also in oxidative enzyme activities and in number of mitochondria, together with an impaired glucose tolerance. However, the role of LPL in intracellular nutrient pathways remains uncertain. To examine differences in muscle nutrient uptake and fatty acid oxidative pattern, transgenic rabbits harboring a DNA fragment of the human LPL gene (hLPL and their wild-type littermates were compared for two muscles of different metabolic type, and for perirenal fat. Results Analyses of skeletal muscles and adipose tissue showed the expression of the hLPL DNA fragment in tissues of the hLPL group only. Unexpectedly, the activity level of LPL in both tissues was similar in the two groups. Nevertheless, mitochondrial fatty acid oxidation rate, measured ex vivo using [1-14C]oleate as substrate, was lower in hLPL rabbits than in wild-type rabbits for the two muscles under study. Both insulin-sensitive glucose transporter GLUT4 and muscle fatty acid binding protein (H-FABP contents were higher in hLPL rabbits than in wild-type littermates for the pure oxidative semimembranosus proprius muscle, but differences between groups did not reach significance when considering the fast-twitch glycolytic longissimus muscle. Variations in both glucose uptake potential, intra-cytoplasmic binding of fatty acids, and lipid oxidation rate observed in hLPL rabbits compared with their wild-type littermates, were not followed by any modifications in tissue lipid content, body fat, and plasma levels in energy-yielding metabolites. Conclusions Expression of intracellular binding proteins for both fatty acids and

A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

International Nuclear Information System (INIS)

Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

1994-01-01

A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

A novel method for the determination of mercury and selenium in shark tissue using high-resolution inductively coupled plasma-mass spectrometry

International Nuclear Information System (INIS)

Paul, Mitchell C.; Toia, Robert F.; Nagy-Felsobuki, Ellak I. von

2003-01-01

A method for measuring Hg and Se in shark tissue by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) has been developed. Using a matrix of 4% (v/v) aqueous methanol, the spray chamber and transfer tubing memory effects of Hg were significantly reduced. The methanol matrix was able to effectively wash out Hg (10 ppb) and return the signal to blank level in approximately 5 min. This enabled accurate and concomitant measurements of Hg and Se with detection limits (3σ blank signal, n=10) of 26 and 4 ppt, respectively. The recoveries of Hg and Se based on the CRM were 88 and 83%, respectively. The concentrations of Hg and Se in the (liver, muscle, kidney) of a hammerhead shark (dry weight) were (2.65±0.85, 7.09±1.32, 4.43±1.36) and (17.3±4.1, 1.28±0.29, 24.1±5.2) mg kg -1 (where the expanded uncertainty uses a k=2 value) respectively. Multi-elemental semi-quantitative analysis of a hammerhead shark liver, muscle and kidney revealed high levels of Cd, Zn and As

FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels.

Directory of Open Access Journals (Sweden)

María Isabel Queipo-Ortuño

Full Text Available BACKGROUND: FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. OBJECTIVE: In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. METHODS: The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. RESULTS: In obesity FABP4 expression was down-regulated (at both mRNA and protein levels, with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. CONCLUSION: The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.

Effects of chromium-enriched bacillus subtilis KT260179 supplementation on chicken growth performance, plasma lipid parameters, tissue chromium levels, cecal bacterial composition and breast meat quality.

Science.gov (United States)

Yang, Jiajun; Qian, Kun; Zhang, Wei; Xu, Yayuan; Wu, Yijing

2016-11-08

Both chromium (Cr) and probiotic bacillus own the virtues of regulating animal metabolism and meat quality. Purpose of this study was to evaluate the efficiency of supplemental Cr and bacillus in the form of chromium-enriched Bacillus subtilis KT260179 (CEBS) on chicken growth performance, plasma lipid parameters, tissue chromium levels, cecal bacterial composition and breast meat quality. Six hundred of 1-day-old Chinese Huainan Partridge chickens were divided into four groups randomly: Control, inorganic Cr, Bacillus subtilis, and CEBS. The feed duration was 56 days. After 28 days of treatment, broiler feed CEBS or normal B. subtilis had higher body weights than control broiler, and after 56 days, chickens given either CEBS or B. subtilis had greater body weights than control broiler or those given inorganic Cr. Plasma total cholesterol, triglycerides, and low density lipoprotein cholesterol levels declined significantly in the CEBS group compared with the control, whereas plasma high density lipoprotein cholesterol levels increased significantly. The concentration of Cr in blood and breast muscle increased after CEBS and inorganic Cr supplementation. B. subtilis and CEBS supplementation caused a significant increase in the numbers of Lactobacillus and Bifidobacterium in the caecum, while the numbers of Escherichia coli and Salmonella decreased significantly compared to the control. Feed adding CEBS increased the lightness, redness, and yellowness of breast meat, improved the water-holding capacity, decreased the shear force and cooking loss. In all, CEBS supplementation promoted body growth, improved plasma lipid parameters, increased tissue Cr concentrations, altered cecal bacterial composition and improved breast meat quality.

Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

Science.gov (United States)

Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

2017-09-01

Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

Insulin sensitivity is independent of lipid binding protein trafficking at the plasma membrane in human skeletal muscle

DEFF Research Database (Denmark)

Jordy, Andreas Børsting; Serup, Annette Karen; Karstoft, Kristian

2014-01-01

The aim of the present study was to investigate lipid-induced regulation of lipid binding proteins in human skeletal muscle and the impact hereof on insulin sensitivity. Eleven healthy male subjects underwent a 3-day hyper-caloric and high-fat diet regime. Muscle biopsies were taken before......-regulated by increased fatty acid availability. This suggests a time dependency in the up-regulation of FAT/CD36 and FABPpm protein during high availability of plasma fatty acids. Furthermore, we did not detect FATP1 and FATP4 protein in giant sarcolemmal vesicles obtained from human skeletal muscle. In conclusion......, this study shows that a short-term lipid-load increases mRNA content of key lipid handling proteins in human muscle. However, decreased insulin sensitivity after high-fat diet is not accompanied with relocation of FAT/CD36 or FABPpm protein to the sarcolemma. Finally, FATP1 and FATP4 protein could...

Pathomorphological features of the skin and muscle tissue of experimental animals in the case of lifetime and postmortem damage

Directory of Open Access Journals (Sweden)

A. V. Kis

2013-04-01

Full Text Available The problem of forensic medical diagnosis of tissue injury is currently the subject of numerous investigations. Pathomorphological changes of the skin and muscle tissue of experimental animals, resulting in the case of lifetime and postmortem traumatic injuries, depending on the time and temperature, were revealed by the author. Data obtained by the author is very necessary for improving the forensic medical diagnosis of traumatic soft tissue injuries.

Freeze drying reduces the extractability of organochlorine pesticides in fish muscle tissue by microwave-assisted method

International Nuclear Information System (INIS)

Zhang, Yanyan; Lin, Nan; Su, Shu; Shen, Guofeng; Chen, Yuanchen; Yang, Chunli; Li, Wei; Shen, Huizhong; Huang, Ye; Chen, Han; Wang, Xilong; Liu, Wenxin; Tao, Shu

2014-01-01

Samples of animal origin are usually dried before solvent extraction for analysis of organic contaminants. The freeze drying technique is preferred for hydrophobic organic compounds in practice. In this study, it was shown that the concentration of organochlorine pesticides (OCPs) extracted from fish muscle tissue significantly decreased after the samples were freeze dried. And the reason for this reduced extractability seemed to be the resistance of OCPs associated with freeze-dried muscle protein to solvent extraction. The extractability can be recovered by adding water prior to extraction. It suggests that the dietary exposure risk of OCPs from fish might be underestimated if freeze-dried samples are used. - Highlights: • Freeze drying significantly reduces extractability of OCPs in fish muscle sample. • It is the protein that causes the reduction in extractability of OCPs. • The extractability can be recovered by adding water before extraction. - Freeze drying significantly decreases the concentrations of OCPs extracted from fish muscle samples by microwave-assisted method

Fatty acid composition of muscle and adipose tissues of indigenous Caribbean goats under varying nutritional densities.

Science.gov (United States)

Liméa, L; Alexandre, G; Berthelot, V

2012-02-01

The effects of a concentrate diet on growth, carcass fat, and fatty acid (FA) composition of muscle (supraspinatus), perirenal, and intermuscular adipose tissues of Creole goats (n = 32) were evaluated. Goats were fed a tropical green forage Digitaria decumbens ad libitum with no concentrate (G0) or 1 of 3 levels of concentrate: 140 (G100), 240 (G200), and 340 g•d(-1) (G300), respectively. Goats were slaughtered according to the standard procedure at the commercial BW (22 to 24 kg of BW). Goats fed the concentrate diets (G100, G200, and G300) had greater ADG (P 0.05). Increased concentrate supplementation did not affect (P > 0.05) the proportion of MUFA in all tissues and had very little effect on SFA in perirenal tissue, but increased the PUFA proportion in muscle (P < 0.05). The major effect of feeding increased concentrate was an increase in n-6 PUFA proportions in all tissues (P < 0.001) and, surprisingly, a decrease in n-3 PUFA (P < 0.001). Focusing on FA, which are supposed to have a beneficial or an adverse effect on human health, feeding increased concentrate did not increase the content of any cholesterol-increasing SFA in meat, but increased the n-6/n-3 ratio above 4 when more than 240 g of concentrate was fed per day.

Quantitative determination of Na+-K+-ATPase and other sarcolemmal components in muscle cells

International Nuclear Information System (INIS)

Hansen, O.; Clausen, T.

1988-01-01

A recurring problem in the characterization of plasma membrane enzymes in tissues and cells is whether the samples tested are representative for the entire population of enzyme molecules present in the starting material. Measurements of [ 3 H]-ouabain binding, enzyme activity, and maximum transport capacity all indicate that the concentration of Na + -K + pumps in mammalian skeletal muscle is high. Studies on Na + -K + -ATPase activity in isolated sarcolemma, however, generally give little or no information on total cellular enzyme concentration. Due to the low and variable enzyme recovery, such subcellular preparations may, therefore, give misleading data on factors regulating Na + -K + -ATPase in heart and skeletal muscle cells. As the same isolation and purification procedures are used for the study of other sarcolemmal components, this inadequate recovery has general implications for statements on regulatory changes in the sarcolemmal composition of muscle cells. On the other hand, complete quantification of Na + -K + -ATPase in muscle tissue can now be achieved using simple procedures and the entire material. Recent studies have shown that regulatory changes in the entire population of Na + -K + pumps in muscle can be quantified in measurements of [ 3 H]-ouabain binding, K + -activated 3-O-methylfluorescein phosphatase activity, as well as maximum ouabain suppressible Na + -K + transport capacity

Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue

Science.gov (United States)

Sanchez, B.; Li, J.; Bragos, R.; Rutkove, S. B.

2014-05-01

Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz-10 MHz frequency range and modeled to a resistivity Cole-Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease.

Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue

International Nuclear Information System (INIS)

Sanchez, B; Li, J; Rutkove, S B; Bragos, R

2014-01-01

Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz–10 MHz frequency range and modeled to a resistivity Cole–Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease. (paper)

Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

Science.gov (United States)

Tylutki, Zofia; Polak, Sebastian

2015-03-12

Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A novel plasma source for sterilization of living tissues

International Nuclear Information System (INIS)

Martines, E; Zuin, M; Cavazzana, R; Gazza, E; Serianni, G; Spagnolo, S; Spolaore, M; Leonardi, A; Deligianni, V; Brun, P; Aragona, M; Castagliuolo, I; Brun, P

2009-01-01

A source for the production of low-power plasmas at atmospheric pressure, to be used for the nondamaging sterilization of living tissues, is presented. The source, powered by radiofrequency and working with a helium flow, has a specific configuration, studied to prevent the formation of electric arcs dangerous to living matter. It is capable of killing different types of bacteria with a decimal reduction time of 1-2 min; on the contrary, human cells such as conjunctival fibroblasts were found to be almost unharmed by the plasma. A high concentration of OH radicals, likely to be the origin of the sterilizing effect, is detected through their UV emission lines. The effect of the UV and the OH radicals on the fibroblasts was analysed and no significant effects were detected.

Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

DEFF Research Database (Denmark)

Liaset, Bjørn; Madsen, Lise; Hao, Qin

2009-01-01

levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal....../retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism....

Muscle-splitting approach to superior and inferior gluteal vessels: versatile source of recipient vessels for free-tissue transfer to sacral, gluteal, and ischial regions.

Science.gov (United States)

Park, S

2000-07-01

The superior gluteal vessel has been reported as a recipient in free-tissue transfer for the coverage of complex soft-tissue defects in the lumbosacral region, where a suitable recipient vessel is difficult to find. The characteristics of proximity, vessel caliber, and constancy make the superior gluteal vessel preferable to previously reported recipient vessels. However, there are technical difficulties in microsurgery (e.g., short pedicle length and deep location) and muscle injury (transection of the muscle) associated with use of the superior gluteal vessel. The purpose of this article is to present a modification of an approach to the gluteal vessel to alleviate technical difficulties and minimize muscle injury. From August of 1997 to January of 1999, six patients received microvascular transfer of the latissimus dorsi muscle or myocutaneous flap to the sacral (4) and ischial (2) regions. The causes of defects were tumor (1), trauma (1), and pressure sores (4). A muscle-splitting approach was used on the superior gluteal vessel and was later applied to the inferior gluteal vessel. The gluteus maximus muscle was split as needed in the direction of its fibers, and the perforators were dissected down to the superior or inferior gluteal artery and vein deep into the muscle. The follow-up period ranged from 6 to 22 months, and all of the flaps survived with complete recovery of the lesion. The major drawbacks of using the superior and inferior gluteal vessels can be overcome with the muscle-splitting approach, which provides increased accessibility and additional length to the vascular pedicle while causing minimal injury to the muscle itself. It also proves to be an easy, safe, and reliable method of dissection. When free-tissue transfer to sacral, gluteal, and ischial regions is indicated, the muscle-splitting approach to the superior and inferior gluteal vessels is a recommended option in the selection of a recipient vessel.

Passive mechanical properties of rat abdominal wall muscles suggest an important role of the extracellular connective tissue matrix.

Science.gov (United States)

Brown, Stephen H M; Carr, John Austin; Ward, Samuel R; Lieber, Richard L

2012-08-01

Abdominal wall muscles have a unique morphology suggesting a complex role in generating and transferring force to the spinal column. Studying passive mechanical properties of these muscles may provide insights into their ability to transfer force among structures. Biopsies from rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA) were harvested from male Sprague-Dawley rats, and single muscle fibers and fiber bundles (4-8 fibers ensheathed in their connective tissue matrix) were isolated and mechanically stretched in a passive state. Slack sarcomere lengths were measured and elastic moduli were calculated from stress-strain data. Titin molecular mass was also measured from single muscle fibers. No significant differences were found among the four abdominal wall muscles in terms of slack sarcomere length or elastic modulus. Interestingly, across all four muscles, slack sarcomere lengths were quite long in individual muscle fibers (>2.4 µm), and demonstrated a significantly longer slack length in comparison to fiber bundles (p resistance to lengthening at long muscle lengths. Titin molecular mass was significantly less in TrA compared to each of the other three muscles (p < 0.0009), but this difference did not correspond to hypothesized differences in stiffness. Copyright © 2012 Orthopaedic Research Society.

Development and application of radioimmunological methods to determine an anabolic compound (trenboloneacetate sup(R)) and its major metabolite (trenbolone) in various tissues and in bovine plasma

International Nuclear Information System (INIS)

Oettel, G.M.

1976-01-01

For quantitation of the anabolic compound trenboloneacetate sup(R)(TBA) and its major metabolite trenbolone (TBOH) a radioimmunoassay (RIA) was established after raising antibodies in rabbits immunized with TBA-3-(o-carboxi-methyl)-oxime-BSA and TBOH-17β-hemisuccinate-BSA. In order to apply this assay for residue determinations in muscle, liver kidney and fat as well as in plasma of treated animals specific extraction procedures were developed. Specifity, sensitivity, accuracy and reproductibility were tested and the developed methods were shown to be highly reliable. Besides free also conjugated TBOH could be determined after enzyme hydrolysis. The lower limit of sensitivity was around 45 pg; at present 100 tissue samples can be analyzed by one person during one week. With the methods described tissue and plasma samples of 41 heifer calves, 10 bull calves and two steers were analyzed for residues of TBA and TBOH. The animals were treated with various dosages of TBA, alone or in combination with oestradiol-17β. In treated animals the highest residue levels were found in liver, with conjugated TBOH being the major residue fraction (76,4%). Second ranking after liver were fat and kidney tissue with similarly high total residue concentrations, however, free TBOH being the major residue fraction (84,1%) in fat, while each, free and conjugated TBOH, accounted for about 50% in kidney. Lowest residue concentrations with free TBOH being the major residue fraction (91,5%) were found in general in muscular tissue. TBA could only be quantitated in fat (14.2% of total residues). (orig.) [de

Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks.

NARCIS (Netherlands)

De Goede, P.; Sen, Satish; Oosterman, Johanneke E; Kalsbeek, A.

2018-01-01

The effects of feeding behavior and diet composition,as well as their possible interactions,on daily (clock) gene expression rhythms have mainly been studied in the liver, and to a lesser degree in white adipose tissue(WAT), but hardly in other metabolic tissues such as skeletal muscle (SM) and

GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response.

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Martha Lappas

Full Text Available Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3 plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM. Thus, the aims of this study were (i to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. In conclusion, GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators.

GLUT-4 content in plasma membrane of muscle from patients with non-insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Lund, S; Vestergaard, H; Andersen, P H

1993-01-01

The abundance of GLUT-4 protein in both total crude membrane and plasma membrane fractions of vastus lateralis muscle from 13 obese non-insulin-dependent diabetes mellitus (NIDDM) patients and 14 healthy subjects were examined in the fasting state and after supraphysiological hyperinsulinemia....... In the basal state the immunoreactive mass of GLUT-4 protein both in the crude membrane preparation and in the plasma membrane fraction was similar in NIDDM patients and control subjects. Moreover, in vivo insulin exposure neither for 30 min nor for 4 h had any impact on the content of GLUT-4 protein in plasma...... membranes. With the use of the same methodology, antibody, and achieving the same degree of plasma membrane purification and recovery, we found, however, that intraperitoneal administration of insulin to 7-wk-old rats within 30 min increased the content of GLUT-4 protein more than twofold (P

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.

Biocompatible, Biodegradable, and Electroactive Polyurethane-Urea Elastomers with Tunable Hydrophilicity for Skeletal Muscle Tissue Engineering.

Science.gov (United States)

Chen, Jing; Dong, Ruonan; Ge, Juan; Guo, Baolin; Ma, Peter X

2015-12-30

It remains a challenge to develop electroactive and elastic biomaterials to mimic the elasticity of soft tissue and to regulate the cell behavior during tissue regeneration. We designed and synthesized a series of novel electroactive and biodegradable polyurethane-urea (PUU) copolymers with elastomeric property by combining the properties of polyurethanes and conducting polymers. The electroactive PUU copolymers were synthesized from amine capped aniline trimer (ACAT), dimethylol propionic acid (DMPA), polylactide, and hexamethylene diisocyanate. The electroactivity of the PUU copolymers were studied by UV-vis spectroscopy and cyclic voltammetry. Elasticity and Young's modulus were tailored by the polylactide segment length and ACAT content. Hydrophilicity of the copolymer films was tuned by changing DMPA content and doping of the copolymer. Cytotoxicity of the PUU copolymers was evaluated by mouse C2C12 myoblast cells. The myogenic differentiation of C2C12 myoblasts on copolymer films was also studied by analyzing the morphology of myotubes and relative gene expression during myogenic differentiation. The chemical structure, thermal properties, surface morphology, and processability of the PUU copolymers were characterized by NMR, FT-IR, gel permeation chromatography (GPC), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and solubility testing, respectively. Those biodegradable electroactive elastic PUU copolymers are promising materials for repair of soft tissues such as skeletal muscle, cardiac muscle, and nerve.

Anterior thigh composition measured using ultrasound imaging to quantify relative thickness of muscle and non-contractile tissue: a potential biomarker for musculoskeletal health

International Nuclear Information System (INIS)

Agyapong-Badu, Sandra; Warner, Martin; Samuel, Dinesh; Stokes, Maria; Narici, Marco; Cooper, Cyrus

2014-01-01

This study aimed to use ultrasound imaging to provide objective data on the effects of ageing and gender on relative thickness of quadriceps muscle and non-contractile tissue thickness (subcutaneous fat, SF, combined with perimuscular fascia). In 136 healthy males and females (aged 18–90 years n = 63 aged 18–35 years; n = 73 aged 65–90) images of the anterior thigh (dominant) were taken in relaxed supine using B-mode ultrasound imaging. Thickness of muscle, SF and perimuscular fascia were measured, and percentage thickness of total anterior thigh thickness calculated. Independent t-tests compared groups. Correlation between tissue thickness and BMI was examined using Pearson’s coefficient. Muscle thickness was: 39  ±  8 mm in young males, 29  ±  6 mm in females, 25  ±  4 mm in older males and 20  ±  5 mm in females. Percentage muscle to thigh thickness was greater in young participants (p = 0.001). Percentage SF and fascia was 17  ±  6% in young and 26  ±  8% in older males, 32  ±  7% in young and 44  ±  7% in older females. BMI was similar for age and correlated moderately with non-contractile tissue (r = 0.54; p < 0.001) and poorly with muscle (r = −0.01; p = 0.93). In conclusion, this novel application of ultrasound imaging as a simple and rapid means of assessing thigh composition (relative thickness of muscle and non-contractile tissue) may help inform health status, e.g. in older people at risk of frailty and loss of mobility, and aid monitoring effects of weight loss or gain, deconditioning and exercise. (paper)

Effect of an aqueous extract of Scoparia dulcis on plasma and tissue glycoproteins in streptozotocin induced diabetic rats.

Science.gov (United States)

Latha, M; Pari, L

2005-02-01

The influence of Scoparia dulcis, a traditionally used plant for the treatment of diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement in glycoprotein levels. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia dulcis plant was administered orally for 6 weeks. The effect of the Scoparia dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins studied was in comparison to glibenclamide. The levels of blood glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin diabetic rats. Oral administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to decreased levels of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that Scoparia dulcis possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect.

A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

Science.gov (United States)

Randolph, Matthew E.; Pavlath, Grace K.

2015-01-01

The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease. PMID:26500547

The effect of repeated freeze-thaw cycles on human muscle tissue visualized by postmortem computed tomography (PMCT)

NARCIS (Netherlands)

Klop, Anthony C.; Vester, Marloes E. M.; Colman, Kerri L.; Ruijter, Jan M.; van Rijn, Rick R.; Oostra, Roelof-Jan

2017-01-01

The aim of this study was to determine whether effects of repetitive freeze-thaw cycles, with various thawing temperatures, on human muscle tissue can be quantified using postmortem computed tomography (PMCT) technology. An additional objective was to determine the preferred thawing temperature for

Muscle Releases Alpha-Sarcoglycan Positive Extracellular Vesicles Carrying miRNAs in the Bloodstream.

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Michele Guescini

Full Text Available In the past few years, skeletal muscle has emerged as an important secretory organ producing soluble factors, called myokines, that exert either autocrine, paracrine or endocrine effects. Moreover, recent studies have shown that muscle releases microRNAs into the bloodstream in response to physical exercise. These microRNAs affect target cells, such as hormones and cytokines. The mechanisms underlying microRNA secretion are poorly characterized at present. Here, we investigated whether muscle tissue releases extracellular vesicles (EVs, which carry microRNAs in the bloodstream under physiological conditions such as physical exercise. Using density gradient separation of plasma from sedentary and physically fit young men we found EVs positive for TSG101 and alpha-sarcoglycan (SGCA, and enriched for miR-206. Cytometric analysis showed that the SGCA+ EVs account for 1-5% of the total and that 60-65% of these EVs were also positive for the exosomal marker CD81. Furthermore, the SGCA-immuno captured sub-population of EVs exhibited higher levels of the miR-206/miR16 ratio compared to total plasma EVs. Finally, a significant positive correlation was found between the aerobic fitness and muscle-specific miRNAs and EV miR-133b and -181a-5p were significantly up-regulated after acute exercise. Thus, our study proposes EVs as a novel means of muscle communication potentially involved in muscle remodeling and homeostasis.

Tissue distribution and elimination of rotenone in rainbow trout

Science.gov (United States)

Gingerich, W.H.

1986-01-01

The fate of a single i.v. dose (120 μg/kg) of the piscicide [14C]rotenone was evaluated in rainbow trout for periods up to 72 h after dosing. Rotenone was rapidly cleared from the plasma; less than 2% of the dose remained in the plasma compartment after 20 min. The highest concentrations of rotenone residues (% dose/g tissue) were in the hepatobiliary system, bile, intestine, and in heart, lateral line swimming muscle, and posterior kidney; tissues that are highly dependent on oxidative metabolism. Although rotenone activity was present in all cell fractions examined, greater than 40% was associated with the mitochondrial fraction of liver, kidney, and muscle. More than 85% of the activity extracted from these tissues, except the liver, was parent rotenone. Elimination from whole body and major tissue depots conformed to simple first-order kinetics; the estimated half-life from whole body was 68.5 h. Branchial elimination accounted for 5% of the injected dose over a 4-h period, and urinary elimination was less than 2% over a 48-h period. Rotenone was eliminated essentially unchanged across the gills; however, parent rotenone was not found in either urine or bile. More than 80% of the activity in both urine and bile eluted from HPLC chromatographs as a highly polar fraction that was not hydrolyzed by incubation with either β-glucuronidase or sulfatase. The results imply that hepatobiliary excretion is the major route of elimination for rotenone residues in the trout and that metabolism to a more polar form is a prerequisite for elimination in both the bile and the urine

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

Energy Technology Data Exchange (ETDEWEB)

Miller, V., E-mail: vmiller@coe.drexel.edu; Lin, A.; Brettschneider, J.; Fridman, G.; Fridman, A. [AJ Drexel Plasma Institute, Drexel University, Camden, New Jersey 08103 (United States); Kako, F.; Gabunia, K.; Kelemen, S.; Autieri, M. [Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 (United States)

2015-12-15

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.

Pathologic bladder microenvironment attenuates smooth muscle differentiation of skin derived precursor cells: implications for tissue regeneration.

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Cornelia Tolg

Full Text Available Smooth muscle cell containing organs (bladder, heart, blood vessels are damaged by a variety of pathological conditions necessitating surgery or organ replacement. Currently, regeneration of contractile tissues is hampered by lack of functional smooth muscle cells. Multipotent skin derived progenitor cells (SKPs can easily be isolated from adult skin and can be differentiated in vitro into contractile smooth muscle cells by exposure to FBS. Here we demonstrate an inhibitory effect of a pathologic contractile organ microenvironment on smooth muscle cell differentiation of SKPs. In vivo, urinary bladder strain induces microenvironmental changes leading to de-differentiation of fully differentiated bladder smooth muscle cells. Co-culture of SKPs with organoids isolated from ex vivo stretched bladders or exposure of SKPs to diffusible factors released by stretched bladders (e.g. bFGF suppresses expression of smooth muscle markers (alpha SMactin, calponin, myocardin, myosin heavy chain as demonstrated by qPCR and immunofluorescent staining. Rapamycin, an inhibitor of mTOR signalling, previously observed to prevent bladder strain induced de-differentiation of fully differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle cell differentiation of undifferentiated SKPs. These results suggest that intended precursor cell differentiation may be paradoxically suppressed by the disease context for which regeneration may be required. Organ-specific microenvironment contexts, particularly prevailing disease, may play a significant role in modulating or attenuating an intended stem cell phenotypic fate, possibly explaining the variable and inefficient differentiation of stem cell constructs in in vivo settings. These observations must be considered in drafting any regeneration strategies.

Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.

Science.gov (United States)

Martin, Neil R W; Turner, Mark C; Farrington, Robert; Player, Darren J; Lewis, Mark P

2017-10-01

The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers.

Science.gov (United States)

Bhaskari, J; Premalata, C S; Shilpa, V; Rahul, B; Pallavi, V R; Ramesh, G; Krishnamoorthy, Lakshmi

2016-01-01

In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well.

Human skeletal muscle releases leptin in vivo

DEFF Research Database (Denmark)

Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

2012-01-01

Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

In Vivo Imaging of Far-red Fluorescent Proteins after DNA Electrotransfer to Muscle Tissue

DEFF Research Database (Denmark)

Hojman, Pernille; Eriksen, Jens; Gehl, Julie

2009-01-01

DNA electrotransfer to muscle tissue yields long-term, high levels of gene expression; showing great promise for future gene therapy. We want to characterize the novel far-red fluorescent protein Katushka as a marker for gene expression using time domain fluorescence in vivo imaging. Highly...... weeks. Depth and 3D analysis proved that the expression was located in the target muscle. In vivo bio-imaging using the novel Katushka fluorescent protein enables excellent evaluation of the transfection efficacy, and spatial distribution, but lacks long-term stability....... efficient transgenic expression was observed after DNA electrotransfer with 100-fold increase in fluorescent intensity. The fluorescent signal peaked 1 week after transfection and returned to background level within 4 weeks. Katushka expression was not as stable as GFP expression, which was detectable for 8...

Tissue types (image)

Science.gov (United States)

... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

Engineering muscle tissue for the fetus: getting ready for a strong life

Directory of Open Access Journals (Sweden)

George Joseph Christ

2015-04-01

Full Text Available Congenital malformations frequently involve either skeletal, smooth or cardiac tissues. When large parts of those tissues are damaged, the repair of the malformations is challenged by the fact that so much autologous tissue is missing. Current treatments require the use of prostheses or other therapies and are associated with a significant morbidity and mortality. Nonetheless, affected children have generally good survival rates and mostly normal schooling. As such, new therapeutic modalities need to represent significant improvements with clear safety profiles. Regenerative medicine and tissue engineering technologies have the potential to dramatically improve the treatment of any disease or disorder involving a lack of viable tissue. With respect to congenital soft tissue anomalies, the development of, for example, implantable muscle constructs would provide not only the usual desired elasticity and contractile proprieties, but should also be able to grow with the fetus and/or in the postnatal life. Such an approach would eliminate the need for multiple surgeries. However, the more widespread clinical applications of regenerative medicine and tissue engineering technologies require identification of the optimal indications, as well as further elucidation of the precise mechanisms and best methods (cells, scaffolds/biomaterials for achieving large functional tissue regeneration in those clinical indications. In short, despite some amazing scientific progress, significant safety and efficacy hurdles remain. However, the rapid preclinical advances in the field bode well for future applications. As such, translational researchers and clinicians alike need be informed and prepared to utilize these new techniques for the benefit of their patients, as soon as they are available. To this end, we review herein, the clinical need(s, potential applications, and the relevant preclinical studies that are currently guiding the field toward novel

Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis

International Nuclear Information System (INIS)

Wun, T.C.; Capuano, A.

1987-01-01

A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig-sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above

Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis

Energy Technology Data Exchange (ETDEWEB)

Wun, T.C.; Capuano, A.

1987-05-01

A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig-sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above.

Congenital hypertrophy of multiple intrinsic muscles of the foot.

Science.gov (United States)

Shiraishi, Tomohiro; Park, Susam; Niu, Atushi; Hasegawa, Hiromi

2014-12-01

Congenital hypertrophy of a single intrinsic muscle of the foot is rare, and as far as we know, only six cases have been reported. We describe a case of congenital anomaly that showed hypertrophy of multiple intrinsic muscles of the foot; the affected muscles were all the intrinsic muscles of the foot except the extensor digitorum brevis or extensor hallucis. Other tissues such as adipose tissue, nervous tissue, or osseous tissue showed no abnormalities. To reduce the volume of the foot we removed parts of the enlarged muscles.

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals

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Coker Robert H

2012-12-01

Full Text Available Abstract Background Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly. Methods In the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR. We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day: 1 EAAMR or a 2 competitive meal replacement (CMR in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR. Results By design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR. Conclusion The provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

* Tissue-Specific Extracellular Matrix Enhances Skeletal Muscle Precursor Cell Expansion and Differentiation for Potential Application in Cell Therapy.

Science.gov (United States)

Zhang, Deying; Zhang, Yong; Zhang, Yuanyuan; Yi, Hualin; Wang, Zhan; Wu, Rongpei; He, Dawei; Wei, Guanghui; Wei, Shicheng; Hu, Yun; Deng, Junhong; Criswell, Tracy; Yoo, James; Zhou, Yu; Atala, Anthony

2017-08-01

Skeletal muscle precursor cells (MPCs) are considered a key candidate for cell therapy in the treatment of skeletal muscle dysfunction due to injury, disease, or age. However, expansion of a sufficient number of functional skeletal muscle cells in vitro from a small tissue biopsy has been challenging due to changes in phenotypic expression of these cells under traditional culture conditions. Thus, the aim of the study was to develop a better culture system for the expansion and myo-differentiation of MPCs that could further be used for therapy. For this purpose, we developed an ideal method of tissue decellularization and compared the ability of different matrices to support MPC growth and differentiation. Porcine-derived skeletal muscle and liver and kidney extracellular matrix (ECM) were generated by decellularization methods consisting of distilled water, 0.2 mg/mL DNase, or 5% fetal bovine serum. Acellular matrices were further homogenized, dissolved, and combined with a hyaluronic acid-based hydrogel decorated with heparin (ECM-HA-HP). The cell proliferation and myogenic differentiation capacity of human MPCs were assessed when grown on gel alone, ECM, or each ECM-HA-HP substrate. Human MPC proliferation was significantly enhanced when cultured on the ECM-HA-HP substrates compared to the other substrates tested, with the greatest proliferation on the muscle ECM-HA-HP (mECM-HA-HP) substrate. The number of differentiated myotubes was significantly increased on the mECM-HA-HP substrate compared to the other gel-ECM substrates, as well as the numbers of MPCs expressing specific myogenic cell markers (i.e., myosin, desmin, myoD, and myf5). In conclusion, skeletal mECM-HA-HP as a culture substrate provided an optimal culture microenvironment potentially due to its similarity to the in vivo environment. These data suggest a potential use of skeletal muscle-derived ECM gel for the expansion and differentiation of human MPCs for cell-based therapy for skeletal muscle

Learning from real and tissue-engineered jellyfish: How to design and build a muscle-powered pump at intermediate Reynolds numbers

Science.gov (United States)

Nawroth, Janna; Lee, Hyungsuk; Feinberg, Adam; Ripplinger, Crystal; McCain, Megan; Grosberg, Anna; Dabiri, John; Parker, Kit

2012-11-01

Tissue-engineered devices promise to advance medical implants, aquatic robots and experimental platforms for tissue-fluid interactions. The design, fabrication and systematic improvement of tissue constructs, however, is challenging because of the complex interactions of living cell, synthetic materials and their fluid environments. In a proof of concept study we have tissue-engineered a construct that mimics the swimming of a juvenile jellyfish, a simple model system for muscle-powered pumps at intermediate Reynolds numbers with quantifiable fluid dynamics and morphological properties. Optimally designed constructs achieved jellyfish-like swimming and generated biomimetic propulsion and feeding currents. Focusing on the fluid interactions, we discuss failed and successful designs and the lessons learned in the process. The main challenges were (1) to derive a body shape and deformation suitable for effective fluid transport under physiological fluid conditions, (2) to understand the mechanical properties of muscle and bell matrix and device a design capable of the desired deformation, (3) to establish adequate 3D kinematics of power and recovery stroke, and (4) to evaluate the performance of the design.

FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration

Science.gov (United States)

Castiglioni, Alessandra; Basso, Veronica; Vezzoli, Michela; Monno, Antonella; Almada, Albert E.; Mondino, Anna; Wagers, Amy J.; Manfredi, Angelo A.; Rovere-Querini, Patrizia

2015-01-01

Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue. PMID:26039259

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...

CT evaluation of soft tissue and muscle infection and inflammation: A systematic compartmental approach

Energy Technology Data Exchange (ETDEWEB)

Beauchamp, N.J. Jr. [Dept. of Radiology, and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, MD (United States); Scott, W.W. Jr. [Dept. of Radiology, and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, MD (United States); Gottlieb, L.M. [Dept. of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD (United States); Fishman, E.K. [Dept. of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD (United States)

1995-07-01

This essay presents a systematic approach to the evaluation of soft tissue and muscle infection by defining the various pathologic processes and then illustrating them through a series of CT studies with corresponding schematic diagrams. The specific processes discussed are cellulitis, lymphangitis/lymphedema, necrotizing fascitis, myositis/myonecrosis, and abscess. Key points in the differential diagnosis of these entities are discussed and illustrated. The clinical management of the specific pathologic processes is also discussed. (orig./MG)

CT evaluation of soft tissue and muscle infection and inflammation: A systematic compartmental approach

International Nuclear Information System (INIS)

Beauchamp, N.J. Jr.; Scott, W.W. Jr.; Gottlieb, L.M.; Fishman, E.K.

1995-01-01

This essay presents a systematic approach to the evaluation of soft tissue and muscle infection by defining the various pathologic processes and then illustrating them through a series of CT studies with corresponding schematic diagrams. The specific processes discussed are cellulitis, lymphangitis/lymphedema, necrotizing fascitis, myositis/myonecrosis, and abscess. Key points in the differential diagnosis of these entities are discussed and illustrated. The clinical management of the specific pathologic processes is also discussed. (orig./MG)

Comments on the paper 'Optical properties of bovine muscle tissue in vitro; a comparison of methods'

International Nuclear Information System (INIS)

Marchesini, R.

1999-01-01

In reply to R. Marchesini's comments that optical values derived by himself and other authors given in the paper entitled 'Optical properties of bovine muscle tissue in vitro; a comparison of methods' were incorrectly cited, the author, J.R. Zijp, apologizes for this mistake and explains the reasons for this misinterpretation. Letter-to-the-editor

Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise

DEFF Research Database (Denmark)

Rosendal, Lars; Søgaard, Karen; Kjaer, Michael

2005-01-01

Interleukin (IL)-6, which is released from muscle tissue during intense exercise, possesses important metabolic and probably anti-inflammatory properties. To evaluate the IL-6 response to low-intensity exercise, we conducted two studies: 1) a control study with insertion of microdialysis catheters...... in muscle and determination of interstitial muscle IL-6 response over 2 h of rest and 2) an exercise study to investigate the IL-6 response to 20 min of repetitive low-force exercise. In both studies, a microdialysis catheter (cutoff: 3,000 kDa) was inserted into the upper trapezius muscle of six male...... subjects, and the catheters were perfused with Ringer-acetate at 5 microl/min. Venous plasma samples were taken in the exercise study. The insertion of microdialysis catheters into muscle resulted in an increase in IL-6 from 8 +/- 0 to 359 +/- 171 and 484 +/- 202 pg/ml after 65 and 110 min, respectively (P...

Determination of piroxicam from rat articular tissue and plasma based on LC-MS/MS.

Science.gov (United States)

Kim, Han Sol; Cho, Ha Ra; Ho, Myoung Jin; Kang, Myung Joo; Choi, Yong Seok

2016-12-01

Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised. Thus, herein, novel LC-MS/MS methods to detect PX in rat articular tissue and plasma are presented. For articular tissue, solvent extraction with acetonitrile for 12 h was employed and a protein precipitation method was used for the preparation of a plasma sample. The developed methods were validated by following the FDA guidelines, and the validated methods were successfully applied to a PK study of IA PX. The present study presents, to our knowledge, the first method of determining a drug in articular tissue. Additionally, the level of PX in articular tissue after IA PX administration was experimentally confirmed for the first time using the present methods. Therefore, the present methods provide a new direction for in vivo evaluation for IA PX formulations and contribute to the development of alternative IA PX formulations with better effects for the treatment of OA.

Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects.

Science.gov (United States)