Polychlorinated biphenyls in the atmosphere of Taizhou, a major e-waste dismantling area in China.

PubMed

Han, Wenliang; Feng, Jialiang; Gu, Zeping; Wu, Minghong; Sheng, Guoying; Fu, Jiamo

2010-01-01

PM2.5, total suspended particles (TSP) and gas phase samples were collected at two sites of Taizhou, a major e-waste dismantling area in China. Concentrations, seasonal variations, congener profiles, gas-particle partitioning and size distribution of the atmospheric polychlorinated biphenyls (PCBs) were studied to assess the current state of atmospheric PCBs after the phase out of massive historical dismantling of PCBs containing e-wastes. The average sigma38PCBs concentration in the ambient air (TSP plus gas phase) near the e-waste dismantling area was (12,407 +/- 9592) pg/m3 in winter, which was substantially lower than that found one decade ago. However, the atmospheric PCBs level near the e-waste dismantling area was 54 times of the reference urban site, indicating that the impact of the historical dismantling of PCBs containing e-wastes was still significant. Tri-Penta-CBs were dominant homologues, consisting with their dominant global production. Size distribution of particle-bound PCBs showed that higher chlorinated CBs tended to partition more to the fine particles, facilitating its long range air transportation.

Low Concentrations of Uncouplers of Oxidative Phosphorylation Prevent Inflammatory Activation of Endothelial Cells by Tumor Necrosis Factor.

PubMed

Romaschenko, V P; Zinovkin, R A; Galkin, I I; Zakharova, V V; Panteleeva, A A; Tokarchuk, A V; Lyamzaev, K G; Pletjushkina, O Yu; Chernyak, B V; Popova, E N

2015-05-01

In endothelial cells, mitochondria play an important regulatory role in physiology as well as in pathophysiology related to excessive inflammation. We have studied the effect of low doses of mitochondrial uncouplers on inflammatory activation of endothelial cells using the classic uncouplers 2,4-dinitrophenol and 4,5,6,7-tetrachloro-2-trifluoromethylbenzimidazole, as well as the mitochondria-targeted cationic uncoupler dodecyltriphenylphosphonium (C12TPP). All of these uncouplers suppressed the expression of E-selectin, adhesion molecules ICAM1 and VCAM1, as well as the adhesion of neutrophils to endothelium induced by tumor necrosis factor (TNF). The antiinflammatory action of the uncouplers was at least partially mediated by the inhibition of NFκB activation due to a decrease in phosphorylation of the inhibitory subunit IκBα. The dynamic concentration range for the inhibition of ICAM1 expression by C12TPP was three orders of magnitude higher compared to the classic uncouplers. Probably, the decrease in membrane potential inhibited the accumulation of penetrating cations into mitochondria, thus lowering the uncoupling activity and preventing further loss of mitochondrial potential. Membrane potential recovery after the removal of the uncouplers did not abolish its antiinflammatory action. Thus, mild uncoupling could induce TNF resistance in endothelial cells. We found no significant stimulation of mitochondrial biogenesis or autophagy by the uncouplers. However, we observed a decrease in the relative amount of fragmented mitochondria. The latter may significantly change the signaling properties of mitochondria. Earlier we showed that both classic and mitochondria-targeted antioxidants inhibited the TNF-induced NFκB-dependent activation of endothelium. The present data suggest that the antiinflammatory effect of mild uncoupling is related to its antioxidant action.

Acute Knockdown of Uncoupling Protein-2 Increases Uncoupling via the Adenine Nucleotide Transporter and Decreases Oxidative Stress in Diabetic Kidneys

PubMed Central

Friederich-Persson, Malou; Aslam, Shakil; Nordquist, Lina; Welch, William J.; Wilcox, Christopher S.; Palm, Fredrik

2012-01-01

Increased O2 metabolism resulting in chronic hypoxia is common in models of endstage renal disease. Mitochondrial uncoupling increases O2 consumption but the ensuing reduction in mitochondrial membrane potential may limit excessive oxidative stress. The present study addressed the hypothesis that mitochondrial uncoupling regulates mitochondria function and oxidative stress in the diabetic kidney. Isolated mitochondria from kidney cortex of control and streptozotocin-induced diabetic rats were studied before and after siRNA knockdown of uncoupling protein-2 (UCP-2). Diabetes resulted in increased UCP-2 protein expression and UCP-2-mediated uncoupling, but normal mitochondria membrane potential. This uncoupling was inhibited by GDP, which also increased the membrane potential. siRNA reduced UCP-2 protein expression in controls and diabetics (−30–50%), but paradoxically further increased uncoupling and markedly reduced the membrane potential. This siRNA mediated uncoupling was unaffected by GDP but was blocked by ADP and carboxyatractylate (CAT). Mitochondria membrane potential after UCP-2 siRNA was unaffected by GDP but increased by CAT. This demonstrated that further increased mitochondria uncoupling after siRNA towards UCP-2 is mediated through the adenine nucleotide transporter (ANT). The increased oxidative stress in the diabetic kidney, manifested as increased thiobarbituric acids, was reduced by knocking down UCP-2 whereas whole-body oxidative stress, manifested as increased circulating malondialdehyde, remained unaffected. All parameters investigated were unaffected by scrambled siRNA. In conclusion, mitochondrial uncoupling via UCP-2 regulates mitochondria membrane potential in diabetes. However, blockade of the diabetes-induced upregulation of UCP- 2 results in excessive uncoupling and reduced oxidative stress in the kidney via activation of ANT. PMID:22768304

Synchronizing noisy nonidentical oscillators by transient uncoupling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tandon, Aditya, E-mail: adityat@iitk.ac.in; Mannattil, Manu, E-mail: mmanu@iitk.ac.in; Schröder, Malte, E-mail: malte@nld.ds.mpg.de

2016-09-15

Synchronization is the process of achieving identical dynamics among coupled identical units. If the units are different from each other, their dynamics cannot become identical; yet, after transients, there may emerge a functional relationship between them—a phenomenon termed “generalized synchronization.” Here, we show that the concept of transient uncoupling, recently introduced for synchronizing identical units, also supports generalized synchronization among nonidentical chaotic units. Generalized synchronization can be achieved by transient uncoupling even when it is impossible by regular coupling. We furthermore demonstrate that transient uncoupling stabilizes synchronization in the presence of common noise. Transient uncoupling works best if the unitsmore » stay uncoupled whenever the driven orbit visits regions that are locally diverging in its phase space. Thus, to select a favorable uncoupling region, we propose an intuitive method that measures the local divergence at the phase points of the driven unit's trajectory by linearizing the flow and subsequently suppresses the divergence by uncoupling.« less

Undergoing, Mystery, and Half-Knowledge: John Dewey's Disquieting Side

ERIC Educational Resources Information Center

d'Agnese, Vasco

2016-01-01

In this article I argue that Dewey, throughout his work, conducted a systematic dismantling of the concept of rationality as mastery and control. Such a dismantling entails, at the same time, the dismantling of the auto-grounded subject, namely, the subject that grounds itself in the power to master experience. The Deweyan challenge to Western…

Know History, Know Self: Art Therapists' Responsibility to Dismantle White Supremacy

ERIC Educational Resources Information Center

Hamrick, Cassie; Byma, Christine

2017-01-01

In this article, we call on white art therapists to assume responsibility for dismantling white supremacy in the field of art therapy, in personal as well as political-structural arenas. We respond to calls from scholars and writers of color for white people to assume increased responsibility for dismantling white supremacy in white communities…

30 CFR 57.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then...

30 CFR 57.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then...

30 CFR 56.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at minimum...

30 CFR 56.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at minimum...

30 CFR 56.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at minimum...

30 CFR 56.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at minimum...

30 CFR 57.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then...

30 CFR 57.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then...

30 CFR 57.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then...

30 CFR 56.14215 - Coupling or uncoupling cars.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at minimum...

Dismantling institutional racism: theory and action.

PubMed

Griffith, Derek M; Mason, Mondi; Yonas, Michael; Eng, Eugenia; Jeffries, Vanessa; Plihcik, Suzanne; Parks, Barton

2007-06-01

Despite a strong commitment to promoting social change and liberation, there are few community psychology models for creating systems change to address oppression. Given how embedded racism is in institutions such as healthcare, a significant shift in the system's policies, practices, and procedures is required to address institutional racism and create organizational and institutional change. This paper describes a systemic intervention to address racial inequities in healthcare quality called dismantling racism. The dismantling racism approach assumes healthcare disparities are the result of the intersection of a complex system (healthcare) and a complex problem (racism). Thus, dismantling racism is a systemic and systematic intervention designed to illuminate where and how to intervene in a given healthcare system to address proximal and distal factors associated with healthcare disparities. This paper describes the theory behind dismantling racism, the elements of the intervention strategy, and the strengths and limitations of this systems change approach.

End-of-Life Vehicle Dismantling and Recycling Enterprises: Developing Directions in China

NASA Astrophysics Data System (ADS)

Wang, Lu; Chen, Ming

2013-08-01

End-of-life vehicle (ELV) dismantling and recycling enterprises are the final disposer of the life-cycle process of vehicles. ELV collecting, dismantling technology, and waste disposal directly affect the recovery rate and the friendliness of vehicles toward the environment. China law stipulates that, by 2017, the recovery rate of vehicles should not be less than 95%, and the recycling rate of materials should not be less than 85%. Therefore, knowing the practical running state of such enterprises is needed. This study investigated four ELV dismantling and recycling enterprises in the Yangzi delta district in China and surveyed the ELV collecting, dismantling technology, policy implementation, and running difficulties. After the comparison with the developed countries, the relevant experiences were drawn, and effective measures were put forward to meet the aims stipulated in the law based on the current practical ELV market in China.

Dismantling of Highly Contaminated Process Installations of the German Reprocessing Facility (WAK) - Status of New Remote Handling Technology - 13287

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dux, Joachim; Friedrich, Daniel; Lutz, Werner

2013-07-01

Decommissioning and dismantling of the former German Pilot Reprocessing Plant Karlsruhe (WAK) including the Vitrification Facility (VEK) is being executed in different Project steps related to the reprocessing, HLLW storage and vitrification complexes /1/. While inside the reprocessing building the total inventory of process equipment has already been dismantled and disposed of, the HLLW storage and vitrification complex has been placed out of operation since vitrification and tank rinsing procedures where finalized in year 2010. This paper describes the progress made in dismantling of the shielded boxes of the highly contaminated laboratory as a precondition to get access to themore » hot cells of the HLLW storage. The major challenges of the dismantling of this laboratory were the high dose rates up to 700 mSv/h and the locking technology for the removal of the hot cell installations. In parallel extensive prototype testing of different carrier systems and power manipulators to be applied to dismantle the HLLW-tanks and other hot cell equipment is ongoing. First experiences with the new manipulator carrier system and a new master slave manipulator with force reflection will be reported. (authors)« less

49 CFR 1242.30 - Dismantling retired road property and depreciation (accounts XX-17-39, XX-18-39, XX-19-39, 62-17...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Dismantling retired road property and depreciation....30 Dismantling retired road property and depreciation (accounts XX-17-39, XX-18-39, XX-19-39, 62-17..., switching and other) in proportion to the separation of common repair and maintenance expenses associated...

Effect of Bizhongxiao decoction and its dismantled formulae on IL-1 and TNF levels in collagen-induced arthritis in rat synovial joints

PubMed Central

2012-01-01

Background Rheumatoid arthritis (RA), a chronic autoimmune disease, affects sufferers in many different ways. Treatment of this chronic condition is particularly challenging. Traditional Chinese Medicine (TCM) provides alternatives. Bizhongxiao decoction (BZX) is a TCM complex, which has been used clinically for many years to treat RA. The purpose of this study is to compare the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels in rats with RA, and to elucidate its mechanism of action. Methods Ninety healthy normal female SD rats were randomly divided into six groups: normal (control), model, BZX decoction, and the three dismantled formulae (I: heat-clearing and detoxication, II: dissipating dampness, and III: blood circulation promotion). Apart from the normal (control) group, the rats in each group were injected subcutaneously with bovine type II collagen and complete Freund adjuvant to establish a collagen-induced arthritis model, so that inhibition of foot swelling in the rats by BZX decoction and its dismantled formulae could be observed. Immunohistochemistry was used to assess the levels of the inflammatory cytokines IL-1 and TNF in synovial joints at various time points. Results Twenty-one days after the model was established, the levels of TNF and IL-1 were significantly higher in the model group, BZX decoction group and dismantled formula groups I, II and III than in the normal controls (P < 0.05). The levels of these cytokines were significantly higher in the model group than the BZX decoction or the three dismantled formula groups (P <0.01). At longer times, the TNF and IL-1 levels in model group rose gradually; those in the BZX decoction and dismantled formula groups were gradually reduced. The cytokine levels in the BZX decoction group were lower than in the three dismantled formula groups and continued to decline. Conclusions BZX decoction and the three dismantled formulae examined down-regulated the inflammatory factors IL-1 and TNF in collagen-induced arthritis rat models, but BZX exerted the strongest effect. PMID:23163934

Targeted mitochondrial uncoupling beyond UCP1 - The fine line between death and metabolic health.

PubMed

Ost, Mario; Keipert, Susanne; Klaus, Susanne

2017-03-01

In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death. Today, novel mitochondria- or tissue-targeted chemical uncouplers with higher safety and therapeutic values are under investigation in order to tackle obesity, diabetes and fatty liver disease. Moreover, in the past 20 years, transgenic mouse models were generated to understand the molecular and metabolic consequences of targeted uncoupling, expressing functional uncoupling protein 1 (UCP1) ectopically in white adipose tissue or skeletal muscle. Similar to the action of chemical mitochondrial uncouplers, UCP1 protein dissipates the proton gradient across the inner mitochondrial membrane, thus allowing maximum activity of the respiratory chain and compensatory increase in oxygen consumption, uncoupled from ATP synthesis. Consequently, targeted mitochondrial uncoupling in adipose tissue and skeletal muscle of UCP1-transgenic mice increased substrate metabolism and ameliorates obesity, hypertriglyceridemia and insulin resistance. Further, muscle-specific decrease in mitochondrial efficiency promotes a cell-autonomous and cell-non-autonomous adaptive metabolic remodeling with increased oxidative stress tolerance. This review provides an overview of novel chemical uncouplers as well as the metabolic consequences and adaptive processes of targeted mitochondrial uncoupling on metabolic health and survival. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Etomoxir-induced increase in UCP3 supports a role of uncoupling protein 3 as a mitochondrial fatty acid anion exporter.

PubMed

Schrauwen, Patrick; Hinderling, Vera; Hesselink, Matthijs K C; Schaart, Gert; Kornips, Esther; Saris, Wim H M; Westerterp-Plantenga, Margriet; Langhans, Wolfgang

2002-10-01

The physiological function of human uncoupling protein-3 is still unknown. Uncoupling protein-3 is increased during fasting and high-fat feeding. In these situations the availability of fatty acids to the mitochondria exceeds the capacity to metabolize fatty acids, suggesting a role for uncoupling protein-3 in handling of non-metabolizable fatty acids. To test the hypothesis that uncoupling protein-3 acts as a mitochondrial exporter of non-metabolizable fatty acids from the mitochondrial matrix, we gave human subjects Etomoxir (which blocks mitochondrial entry of fatty acids) or placebo in a cross-over design during a 36-h stay in a respiration chamber. Etomoxir inhibited 24-h fat oxidation and fat oxidation during exercise by approximately 14-19%. Surprisingly, uncoupling protein-3 content in human vastus lateralis muscle was markedly up-regulated within 36 h of Etomoxir administration. Up-regulation of uncoupling protein-3 was accompanied by lowered fasting blood glucose and increased translocation of glucose transporter-4. These data support the hypothesis that the physiological function of uncoupling protein-3 is to facilitate the outward transport of non-metabolizable fatty acids from the mitochondrial matrix and thus prevents mitochondria from the potential deleterious effects of high fatty acid levels. In addition our data show that up-regulation of uncoupling protein-3 can be beneficial in the treatment of type 2 diabetes.

Concepts and Tests for the Remote-Controlled Dismantling of the Biological Shield and Form work of the KNK Reactor - 13425

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neff, Sylvia; Graf, Anja; Petrick, Holger

The compact sodium-cooled nuclear reactor facility Karlsruhe (KNK), a prototype Fast Breeder, is currently in an advanced stage of dismantling. Complete dismantling is based on 10 partial licensing steps. In the frame of the 9. decommissioning permit, which is currently ongoing, the dismantling of the biological shield is foreseen. The biological shield consists of heavy reinforced concrete with built-in steel fitments, such as form-work of the reactor tank, pipe sleeves, ventilation channels, and measuring devices. Due to the activation of the inner part of the biological shield, dismantling has to be done remote-controlled. During a comprehensive basic design phase amore » practical dismantling strategy was developed. Necessary equipment and tools were defined. Preliminary tests revealed that hot wire plasma cutting is the most favorable cutting technology due to the geometrical boundary conditions, the varying distance between cutter and material, and the heavy concrete behind the steel form-work. The cutting devices will be operated remotely via a carrier system with an industrial manipulator. The carrier system has expandable claws to adjust to the varying diameter of the reactor shaft during dismantling progress. For design approval of this prototype development, interaction between manipulator and hot wire plasma cutting was tested in a real configuration. For the demolition of the concrete structure, an excavator with appropriate tools, such as a hydraulic hammer, was selected. Other mechanical cutting devices, such as a grinder or rope saw, were eliminated because of concrete containing steel spheres added to increase the shielding factor of the heavy concrete. Dismantling of the biological shield will be done in a ring-wise manner due to static reasons. During the demolition process, the excavator is positioned on its tripod in three concrete recesses made prior to the dismantling of the separate concrete rings. The excavator and the manipulator carrier system will be operated alternately. Main boundary condition for all the newly designed equipment is the decommissioning housing of limited space within the reactor building containment. To allow for a continuous removal of the concrete rubble, an additional opening on the lowest level of the reactor shaft will be made. All equipment and the interaction of the tools have to be tested before use in the controlled area. Therefore a full-scale model of the biological shield will be provided in a mock-up. The tests will be performed in early 2014. The dismantling of the biological shield is scheduled for 2015. (authors)« less

[Interaction of free fatty acids with mitochondria during uncoupling of oxidative phosphorylation].

PubMed

Samartsev, V N; Rybakova, S R; Dubinin, M V

2013-01-01

The activity of free saturated fatty acids (caprylic, capric, lauric, myristic, palmitic and stearic) as inducers and regulators of uncoupling of oxidative phosphorylation with participation of ADP/ATP antiporter, aspartate/glutamate antiporter and cyclosporin A-sensitive structure was investigated in experiments on rat liver mitochondria. It is established that at equal uncoupling activity of fatty acids the regulatory effect is minimal for caprylic acid and raised with increasing the hydrophobicity of fatty acids reaching the maximum value for stearic acid. There exists the linear dependence of the regulatory effect value of fatty acids on fatty acids content in the hydrophobic region of the inner membrane. The model that describes the interaction of fatty acids with the hydrophobic region of the mitochondrial inner membrane preserving functional activity of organelles is developed. It is established that if molecules of various fatty acids being in the hydrophobic region of the membrane are equally effective as uncoupling regulators, their specific uncoupling activity is different. Caprylic acid, a short-chain fatty acid, possesses the highest uncoupling activity. As the acyl chain length increases, the specific uncoupling activity of fatty acids reduces exponentially. Under these conditions components of the uncoupling activity sensitive to glutamate and carboxyatractylate and glutamate and insensitive to these reagents (but sensitive to cyclosporin A) change approximately equally.

Pollution profiles and health risk assessment of VOCs emitted during e-waste dismantling processes associated with different dismantling methods.

PubMed

An, Taicheng; Huang, Yong; Li, Guiying; He, Zhigui; Chen, Jiangyao; Zhang, Chaosheng

2014-12-01

Pollution profiles of typical volatile organic compounds (VOCs) emitted during dismantling of various printed circuit board assemblies (PCBAs) of e-wastes using different methods were comparatively investigated in the real e-waste dismantling workshops in South China in April 2013. Similar pollution profiles and concentrations of VOCs were observed between dismantling mobile phone and hard disk PCBAs by using electric blowers and between dismantling television and power supplier PCBAs using electric heating furnaces. Aromatic hydrocarbons (accounting for >60% of the sum of VOCs) were the dominant group during using electric blowers, while aromatic (accounting for >44% of the sum of VOCs) and halogenated hydrocarbons (accounting for >48% of the sum of VOCs) were the two dominant groups which contributed equally using electric heating furnaces. However, the distribution profiles of VOCs emitted during dismantling of televisions, hard disks and micro motors using rotary incinerators varied greatly, though aromatic hydrocarbons were still the dominant group. The combustion of e-wastes led to the most severe contamination of VOCs, with total VOCs (3.3×10(4) μg m(-3)) using rotary incinerators about 190, 180, 139, and 40 times higher than those using mechanical cutting, electric soldering iron, electric blower, and electric heating furnace, respectively. Both cancer and non-cancer risks existed for workers due to exposure to on-site emitted VOCs in all workshops especially in those using rotary incinerators according to the USEPA methodology, whereas only cancer risks existed in rotary incinerator workshops according to the American Conference of Industrial Hygienists methodology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Endocrine regulation of uncoupling proteins and energy expenditure.

PubMed

Ricquier, D; Miroux, B; Larose, M; Cassard-Doulcier, A M; Bouillaud, F

2000-06-01

Regulatory thermogenesis occurs upon exposure to the cold or during food intake. Among a variety of mechanisms leading to heat production, uncoupling of respiration in brown adipocyte mitochondria appears to be a major contributor to resistance to the cold in rodents. This uncoupling mechanism is due to the activity of uncoupling protein-1 (UCP-1), a specific carrier present in the inner membrane of mitochondria. The recent identification of UCP-2 and UCP-3, two homologues of the brown fat UCP, suggested that respiration uncoupling could contribute to thermogenesis in most tissues. Activity and expression of the three UCP's are stimulated by several neuromediators and hormones such as noradrenaline, tri-iodothyronine and leptin.

[A correlation between respiration and synthesis of ATP in mitochondria at different degree of uncoupling of oxidative phosphorylation].

PubMed

Samartsev, V N; Kozhina, O V; Polishchuk, L S

2005-01-01

It is known that mitochondrial respiration in state 3 is due to three simultaneous and independent processes: synthesis of ATP (1), endogenous passive proton leakage (2), and proton leakage by protonophoric uncoupler (3). The total rate of processes (2) and (3) is equal to the product of respiration rate in state 4 and coefficient KR, which is defined as the ratio of the deltamuH+ value in state 3 to that in state 4. It is shown that it is possible to calculate both the rates of processes (1), (2) and (3) separately and the protonophoric activity of uncoupler using the coefficient KR and other coefficients, which are determined as the ratio of deltamuH+ values in state 3 or in state 4 to its maximal value. Simple methods of determination of these coefficients were developed, which are based on the study of the dependence of respiration rate in states 3 and 4 on the concentration of protonophoric uncoupler. It was found that the uncoupling action of palmitate, a natural uncoupler of oxidative phosphorylation, unlike classic uncoupler-protonophores DNP and FCCP, depends not only on its protonophoric activity but also on the inhibition of the process (1).

Endothermy in birds: underlying molecular mechanisms.

PubMed

Walter, Isabel; Seebacher, Frank

2009-08-01

Endothermy is significant in vertebrate evolution because it changes the relations between animals and their environment. How endothermy has evolved in archosaurs (birds, crocodiles and dinosaurs) is controversial especially because birds do not possess brown adipose tissue, the specialized endothermic tissue of mammals. Internal heat production is facilitated by increased oxidative metabolic capacity, accompanied by the uncoupling of aerobic metabolism from energy (ATP) production. Here we show that the transition from an ectothermic to an endothermic metabolic state in developing chicken embryos occurs by the interaction between increased basal ATP demand (Na(+)/K(+)-ATPase activity and gene expression), increased oxidative capacity and increased uncoupling of mitochondria; this process is controlled by thyroid hormone via its effect on PGC1alpha and adenine nucleotide translocase (ANT) gene expression. Mitochondria become more uncoupled during development, but unlike in mammals, avian uncoupling protein (avUCP) does not uncouple electron transport from oxidative phosphorylation and therefore plays no role in heat production. Instead, ANT is the principal uncoupling protein in birds. The relationship between oxidative capacity and uncoupling indicates that there is a continuum of phenotypes that fall between the extremes of selection for increased heat production and increased aerobic activity, whereas increased cellular ATP demand is a prerequisite for increased oxidative capacity.

Uncoupling protein-3 lowers reactive oxygen species production in isolated mitochondria

PubMed Central

Toime, Laurence J.; Brand, Martin D.

2010-01-01

Mitochondria are the major cellular producers of reactive oxygen species (ROS), and mitochondrial ROS production increases steeply with increased protonmotive force. The uncoupling proteins (UCP1, UCP2 and UCP3) and adenine nucleotide translocase induce proton leak in response to exogenously added fatty acids, superoxide or lipid peroxidation products. “Mild uncoupling” by these proteins may provide a negative feedback loop to decrease protonmotive force and attenuate ROS production. Using wild type and Ucp3−/− mice, we found that native UCP3 actively lowers the rate of ROS production in isolated energized skeletal muscle mitochondria, in the absence of exogenous activators. The estimated specific activity of UCP3 in lowering ROS production was 90 to 500 times higher than that of the adenine nucleotide translocase. The mild uncoupling hypothesis was tested by measuring whether the effect of UCP3 on ROS production could be mimicked by chemical uncoupling. A chemical uncoupler mimicked the effect of UCP3 at early time points after mitochondrial energization, in support of the mild uncoupling hypothesis. However, at later time points the uncoupler did not mimic UCP3, suggesting that UCP3 can also affect on ROS production through a membrane potential-independent mechanism. PMID:20493945

Uncoupling and Turnover in a Cl−/H+ Exchange Transporter

PubMed Central

Walden, Michael; Accardi, Alessio; Wu, Fang; Xu, Chen; Williams, Carole; Miller, Christopher

2007-01-01

The CLC-family protein CLC-ec1, a bacterial homologue of known structure, stoichiometrically exchanges two Cl− for one H+ via an unknown membrane transport mechanism. This study examines mutations at a conserved tyrosine residue, Y445, that directly coordinates a Cl− ion located near the center of the membrane. Mutations at this position lead to “uncoupling,” such that the H+/Cl− transport ratio decreases roughly with the volume of the substituted side chain. The uncoupled proteins are still able to pump protons uphill when driven by a Cl− gradient, but the extent and rate of this H+ pumping is weaker in the more uncoupled variants. Uncoupling is accompanied by conductive Cl− transport that is not linked to counter-movement of H+, i.e., a “leak.” The unitary Cl− transport rate, measured in reconstituted liposomes by both a conventional initial-velocity method and a novel Poisson dilution approach, is ∼4,000 s−1 for wild-type protein, and the uncoupled mutants transport Cl− at similar rates. PMID:17389248

Visual information underpinning skilled anticipation: The effect of blur on a coupled and uncoupled in situ anticipatory response.

PubMed

Mann, David L; Abernethy, Bruce; Farrow, Damian

2010-07-01

Coupled interceptive actions are understood to be the result of neural processing-and visual information-which is distinct from that used for uncoupled perceptual responses. To examine the visual information used for action and perception, skilled cricket batters anticipated the direction of balls bowled toward them using a coupled movement (an interceptive action that preserved the natural coupling between perception and action) or an uncoupled (verbal) response, in each of four different visual blur conditions (plano, +1.00, +2.00, +3.00). Coupled responses were found to be better than uncoupled ones, with the blurring of vision found to result in different effects for the coupled and uncoupled response conditions. Low levels of visual blur did not affect coupled anticipation, a finding consistent with the comparatively poorer visual information on which online interceptive actions are proposed to rely. In contrast, some evidence was found to suggest that low levels of blur may enhance the uncoupled verbal perception of movement.

A novel dismantling process of waste printed circuit boards using water-soluble ionic liquid.

PubMed

Zeng, Xianlai; Li, Jinhui; Xie, Henghua; Liu, Lili

2013-10-01

Recycling processes for waste printed circuit boards (WPCBs) have been well established in terms of scientific research and field pilots. However, current dismantling procedures for WPCBs have restricted the recycling process, due to their low efficiency and negative impacts on environmental and human health. This work aimed to seek an environmental-friendly dismantling process through heating with water-soluble ionic liquid to separate electronic components and tin solder from two main types of WPCBs-cathode ray tubes and computer mainframes. The work systematically investigates the influence factors, heating mechanism, and optimal parameters for opening solder connections on WPCBs during the dismantling process, and addresses its environmental performance and economic assessment. The results obtained demonstrate that the optimal temperature, retention time, and turbulence resulting from impeller rotation during the dismantling process, were 250 °C, 12 min, and 45 rpm, respectively. Nearly 90% of the electronic components were separated from the WPCBs under the optimal experimental conditions. This novel process offers the possibility of large industrial-scale operations for separating electronic components and recovering tin solder, and for a more efficient and environmentally sound process for WPCBs recycling. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical oxygen-iodine laser (COIL) for the dismantlement of nuclear facilities

NASA Astrophysics Data System (ADS)

Hallada, Marc R.; Seiffert, Stephan L.; Walter, Robert F.; Vetrovec, John

2000-05-01

The dismantlement of obsolete nuclear facilities is a major challenge for both the US Department of Energy and nuclear power utilities. Recent demonstrations have shown that lasers can be highly effective for size reduction cutting, especially for the efficient storage and recycling of materials. However, the full benefits of lasers can only be realized with high average power beams that can be conveniently delivered, via fiber optics, to remote and/or confined areas. Industrial lasers that can meet these requirements are not available now or for the foreseeable future. However, a military weapon laser, a Chemical Oxygen Iodine Laser (COIL), which has been demonstrated at over a hundred kilo Watts, could be adapted to meet these needs and enable entirely new industrial applications. An 'industrialized' COIL would enable rapid sectioning of thick and complex structures, such as glove boxes, reactor vessels, and steam generators, accelerating dismantlement schedules and reducing worker hazards. The full advantages of lasers in dismantlement could finally be realized with a portable COIL which is integrated with sophisticated robotics. It could be built and deployed in less than two years, breaking the paradigm of labor-intensive dismantlement operations and cutting processing times and costs dramatically.

49 CFR 215.125 - Defective uncoupling device.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Draft System § 215.125 Defective uncoupling device. A railroad may not place or continue in service a car, if the car has an uncoupling device without sufficient vertical and lateral clearance to prevent— (a...

49 CFR 215.125 - Defective uncoupling device.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Draft System § 215.125 Defective uncoupling device. A railroad may not place or continue in service a car, if the car has an uncoupling device without sufficient vertical and lateral clearance to prevent— (a...

49 CFR 215.125 - Defective uncoupling device.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Draft System § 215.125 Defective uncoupling device. A railroad may not place or continue in service a car, if the car has an uncoupling device without sufficient vertical and lateral clearance to prevent— (a...

49 CFR 215.125 - Defective uncoupling device.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Draft System § 215.125 Defective uncoupling device. A railroad may not place or continue in service a car, if the car has an uncoupling device without sufficient vertical and lateral clearance to prevent— (a...

49 CFR 215.125 - Defective uncoupling device.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Draft System § 215.125 Defective uncoupling device. A railroad may not place or continue in service a car, if the car has an uncoupling device without sufficient vertical and lateral clearance to prevent— (a...

Impaired Adaptability of in Vivo Mitochondrial Energetics to Acute Oxidative Insult in Aged Skeletal Muscle

PubMed Central

Siegel, Michael P.; Wilbur, Tim; Mathis, Mark; Shankland, Eric; Trieu, Atlas; Harper, Mary-Ellen; Marcinek, David J.

2012-01-01

Periods of elevated reactive oxygen species (ROS) production are a normal part of mitochondrial physiology. However, little is known about age-related changes in the mitochondrial response to elevated ROS in vivo. Significantly, ROS-induced uncoupling of oxidative phosphorylation has received attention as a negative feedback mechanism to reduce mitochondrial superoxide production. Here we use a novel in vivo spectroscopy system to test the hypothesis that ROS-induced uncoupling is diminished in aged mitochondria. This system simultaneously acquires 31P magnetic resonance and near-infrared optical spectra to non-invasively measure phosphometabolite and O2 concentrations in mouse skeletal muscle. Using low dose paraquat to elevate intracellular ROS we assess in vivo mitochondrial function in young, middle aged, and old mice. Oxidative phosphorylation was uncoupled to the same degree in response to ROS at each age, but this uncoupling was associated with loss of phosphorylation capacity and total ATP in old mice only. Using mice lacking UCP3 we demonstrate that this in vivo uncoupling is independent of this putative uncoupler of skeletal muscle mitochondria. These data indicate that ROS-induced uncoupling persists throughout life, but that oxidative stress leads to mitochondrial deficits and loss of ATP in aged organisms that may contribute to impaired function and degeneration. PMID:22935551

Large enhancement of skeletal muscle cell glucose uptake and suppression of hepatocyte glucose-6-phosphatase activity by weak uncouplers of oxidative phosphorylation.

PubMed

Martineau, Louis C

2012-02-01

Perturbation of energy homeostasis in skeletal muscle and liver resulting from a transient inhibition of mitochondrial energy transduction can produce effects of relevance for the control of hyperglycemia through activation of the AMP-activated protein kinase, as exemplified by the antidiabetic drug metformin. The present study focuses on uncoupling of oxidative phosphorylation rather than its inhibition as a trigger for such effects. The reference weak uncoupler 2,4-dinitrophenol, fourteen naturally-occurring phenolic compounds identified as uncouplers in isolated rat liver mitochondria, and fourteen related compounds with little or no uncoupling activity were tested for enhancement of glucose uptake in differentiated C2C12 skeletal muscle cells following 18 h of treatment at 25-100 μM. A subset of compounds were tested for suppression of glucose-6-phosphatase (G6Pase) activity in H4IIE hepatocytes following 16 h at 12.5-25 μM. Metformin (400 μM) was used as a standard in both assays. Dinitrophenol and nine of eleven compounds that induced 50% or more uncoupling at 100 μM in isolated mitochondria enhanced basal glucose uptake by 53 to 269%; the effect of the 4'-hydroxychalcone butein was more than 6-fold that of metformin; negative control compounds increased uptake by no more than 25%. Dinitrophenol and four 4'-hydroxychalconoids also suppressed hepatocyte G6Pase as well as, or more effectively than metformin, whereas the unsubstituted parent compound chalcone, devoid of uncoupling activity, had no effect. Activities key to glycemic control can be induced by a wide range of weak uncouplers, including compounds free of difficult-to-metabolize groups typically associated with uncouplers. Uncoupling represents a valid and possibly more efficient alternative to inhibition for triggering cytoprotective effects of therapeutic relevance to insulin resistance in both muscle and liver. Identification of actives of natural origin and the insights into their structure-activity relationship reported herein may lead to alternatives to metformin. Copyright © 2011 Elsevier B.V. All rights reserved.

Decommissioning, Dismantling and Disarming: a Unique Information Showroom Inside the G2 Reactor at Marcoule Centre (France) - 12068

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volant, Emmanuelle; Garnier, Cedric

2012-07-01

The paper aims at presenting the new information showroom called 'Escom G2' (for 'Espace Communication') inaugurated by the French Atomic Energy and Alternative Energies Commission (CEA) in spring 2011. This showroom is settled directly inside the main building of the G2 nuclear reactor: a facility formerly dedicated to weapon-grade plutonium production since the late 1950's at the Marcoule nuclear centre, in south of France. After its shutdown, and reprocessing of the last spent fuels, a first dismantling step was successfully completed from 1986 to 1996. Unique in France and in Europe, Escom G2 is focused on France dismantling expertise andmore » its action for disarmament. This showroom comprises of a 300-square meters permanent exhibition, organized around four themes: France strategy for disarmament, decommissioning and dismantling technical aspects, uranium and plutonium production cycles. Each of these topics is illustrated with posters, photos, models and technical pieces from the dismantled plants. It is now used to present France's action in disarmament to highly ranked audiences such as: state representatives, diplomats, journalists... The paper explains the background story of this original project. As a matter of fact, in 1996 France was the first nuclear state to decide to shut down and dismantle its fissile material production facilities for nuclear weapons. First, the paper presents the history of the G2 reactor in the early ages of Marcoule site, its operating highlights as well as its main dismantling operations, are presented. In Marcoule, where the three industrial-scale reactors G1, G2 and G3 used to be operated for plutonium production (to be then reprocessed in the nearby UP1 plant), the initial dismantling phase has now been completed (in 1980's for G1 and in 1996 for G2 and G3). The second phase, aimed at completely dismantling these three reactors, will restart in 2020, and is directly linked to the opening of a future national storage facility for irradiated graphite waste. Then, the paper recalls communication events and official visits hosted in Pierrelatte and Marcoule, following a formal invitation from the French President Mr. Nicolas Sarkozy. These visits, which were organized in order to illustrate the irreversibility of these dismantling operations, allowed visitors to discovers places that used to be former highly classified areas. Three official visits were organized in 2008 and 2009 for representatives of the Conference on Disarmament Member States, non-governmental experts and journalists. All participants visited the dismantled uranium enrichment plant in Pierrelatte, the G2 reactor and the UP1 plant in Marcoule. The visits were successful and visitors were especially impressed by the G2 reactor and its massive industrial architecture, symbolic of the early ages of nuclear history. In late 2010, this feedback convinced CEA Military Application Directorate (CEA DAM) that a permanent showroom could be installed inside the reactor, making it possible to preserve the cultural value of this historical landmark, and to continue its ongoing effort of communication and outreach. The paper explains the design of this concept: the museography project with a professional designer, the communication material conception and the features of such an original place. (authors)« less

Urinary heavy metal levels and relevant factors among people exposed to e-waste dismantling.

PubMed

Wang, Hongmei; Han, Mei; Yang, Suwen; Chen, Yanqing; Liu, Qian; Ke, Shen

2011-01-01

Primitive electronic waste (e-waste) recycling has become a growing environmental concern, and toxic heavy metals released from e-waste activities may continue to threaten the health of local people. To study the impact of heavy metals in people around e-waste sites, 349 people from e-waste recycling sites (exposure group) and 118 people from a green plantation (control group) were surveyed, and their urinary levels of lead (UPb), cadmium (UCd), manganese (UMn), copper (UCu), and Zinc (UZn) were assayed. Questionnaire surveys for risk factors were also performed and analyzed by using the Pearson correlation analysis. Results indicated that the levels of urinary Cd in both occupational dismantling people {GM(GSD) 0.72(0.71) ug/L} and non-occupational dismantling people {GM(GSD) 0.50(0.79) ug/L} were higher than the control group {GM(GSD) 0.27(0.85) ug/L}. Further analyses of correlations between urinary heavy metal levels and exposure factors in the exposed group revealed positive relationship between the duration of dismantling and the level of UPb (p < 0.05). Meanwhile, rice sources from local village have a positive correlation with the level of UPb and UCd (p < 0.01). Other factors, however, may also have influences on heavy metal burden, and not all urinary heavy metal levels can be contributed to e-waste dismantling exposure levels. Primitive e-waste recycling activities may contribute to the changes of urinary heavy metal levels and increase the health risk for those chronically working on e-waste dismantling. Copyright © 2010 Elsevier Ltd. All rights reserved.

Uncoupling protein expression in skeletal muscle and adipose tissue in response to in vivo porcine somatotropin treatment

USDA-ARS?s Scientific Manuscript database

The uncoupling proteins are thought to be involved in waste heat production, reducing the energy efficiency of growth in animals. Previous studies have detected their presence in swine and their regulation by the endocrine system. This study attempted to determine whether the uncoupling proteins 2...

The mechanism of uncoupling by picrate in Escherichia coli K-12 membrane systems.

PubMed

Michels, M; Bakker, E P

1981-06-01

The mechanism of action of the uncoupler picrate on intact cells and everted membrane vesicles of Escherichia coli K-12 was investigated. Like in mitochondria [Hanstein, W. G. and Hatefi, Y. (1974) Proc. Natl Acad. Sci. USA, 71, 288-292], it was observed that picrate uncoupled energy-linked functions only in everted, but not in intact membrane systems. In the vesicles picrate also decreased the magnitude of the transmembrane proton-motive force at concentrations similar to those at which it caused uncoupling. Experiments with 14C-labelled picrate showed that this compound bound both to deenergized intact cells and everted vesicles. However, upon energization of the membrane, picrate was extruded from the intact cell and taken up to a larger extent by the vesicles. These energy-dependent changes in picrate uptake correlated with the magnitude of the transmembrane electrical potential, delta psi. It is therefore proposed that picrate is a permeant uncoupler, that delta psi is the driving force for picrate movement across biological membranes, and that the uncoupling activity of picrate in everted membrane systems is due to its protonophoric action.

Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle.

PubMed

Roy, Pauline; Rau, Fredérique; Ochala, Julien; Messéant, Julien; Fraysse, Bodvael; Lainé, Jeanne; Agbulut, Onnik; Butler-Browne, Gillian; Furling, Denis; Ferry, Arnaud

2016-01-01

The greater susceptibility to contraction-induced skeletal muscle injury (fragility) is an important dystrophic feature and tool for testing preclinic dystrophin-based therapies for Duchenne muscular dystrophy. However, how these therapies reduce the muscle fragility is not clear. To address this question, we first determined the event(s) of the excitation-contraction cycle which is/are altered following lengthening (eccentric) contractions in the mdx muscle. We found that the immediate force drop following lengthening contractions, a widely used measure of muscle fragility, was associated with reduced muscle excitability. Moreover, the force drop can be mimicked by an experimental reduction in muscle excitation of uninjured muscle. Furthermore, the force drop was not related to major neuromuscular transmission failure, excitation-contraction uncoupling, and myofibrillar impairment. Secondly, and importantly, the re-expression of functional truncated dystrophin in the muscle of mdx mice using an exon skipping strategy partially prevented the reductions in both force drop and muscle excitability following lengthening contractions. We demonstrated for the first time that (i) the increased susceptibility to contraction-induced muscle injury in mdx mice is mainly attributable to reduced muscle excitability; (ii) dystrophin-based therapy improves fragility of the dystrophic skeletal muscle by preventing reduction in muscle excitability.

p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

PubMed Central

2014-01-01

Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Methods Obesity was induced in wild type (WT) and Arg-II-deficient (Arg-II-/-) mice on C57BL/6 J background by high-fat diet (HFD, 55% fat) for 14 weeks starting from age of 7 weeks. The entire aortas were isolated and subjected to 1) immunoblotting analysis of the protein level of eNOS, Arg-II and p38mapk activation; 2) arginase activity assay; 3) endothelium-dependent and independent vasomotor responses; 4) en face staining of superoxide anion and NO production with Dihydroethidium and 4,5-Diaminofluorescein Diacetate, respectively, to assess eNOS-uncoupling. To evaluate the role of p38mapk, isolated aortas were treated with p38mapk inhibitor SB203580 (10 μmol/L, 1 h) prior to the analysis. In addition, the role of p38mapk in Arg-II-induced eNOS-uncoupling was investigated in cultured human endothelial cells overexpressing Arg-II in the absence or presence of shRNA against p38mapk. Results HFD enhanced Arg-II expression/activity and p38mapk activity, which was associated with eNOS-uncoupling as revealed by decreased NO and enhanced L-NAME-inhibitable superoxide in aortas of WT obese mice. In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II-/- obese mice were protected from HFD-induced eNOS-uncoupling and endothelial dysfunction, which was associated with reduced p38mapk activation in aortas of the Arg-II-/- obese mice. Moreover, overexpression of Arg-II in human endothelial cells caused eNOS-uncoupling and augmented p38mapk activation. The Arg-II-induced eNOS-uncoupling was prevented by silencing p38mapk. Furthermore, pharmacological inhibition of p38mapk recouples eNOS in isolated aortas from WT obese mice. Conclusions Taking together, we demonstrate here for the first time that Arg-II causes eNOS-uncoupling through activation of p38 mapk in HFD-induced obesity. PMID:25034973

Pick-N-Pull Auto Dismantlers, Kansas City, LLC Inc.

EPA Pesticide Factsheets

The EPA is providing notice of a proposed Administrative Penalty Assessment against Pick-N-Pull Auto Dismantlers, Kansas City, LLC, a subsidiary of Schnitzer Steel Industries, Inc., for alleged violations at its facilities at 8012 East Truman Rd., Kansas C

Comparison of ship dismantling processes in India and the U.S.

NASA Astrophysics Data System (ADS)

Ahluwalia, Rashpal S.; Sibal, Pooja; Govindarajulu, Sriram

2004-03-01

This paper compares ship-dismantling processes in India and the U.S. The information for India was collected during an informal visit to the ship dismantling sites in Alang, India. The information for the U.S. was obtained from the MARAD report. For a 10,000-ton passenger ship, the Indian contractor makes a profit of about 24% compared to a loss of about 15% in the U.S. The loss in the US is primarily due to high labor costs, compliance to safety and health regulations and lack of market for used components and scrap metal.

Sustainable design for automotive products: dismantling and recycling of end-of-life vehicles.

PubMed

Tian, Jin; Chen, Ming

2014-02-01

The growth in automotive production has increased the number of end-of-life vehicles (ELVs) annually. The traditional approach ELV processing involves dismantling, shredding, and landfill disposal. The "3R" (i.e., reduce, reuse, and recycle) principle has been increasingly employed in processing ELVs, particularly ELV parts, to promote sustainable development. The first step in processing ELVs is dismantling. However, certain parts of the vehicle are difficult to disassemble and use in practice. The extended producer responsibility policy requires carmakers to contribute in the processing of scrap cars either for their own developmental needs or for social responsibility. The design for dismantling approach can be an effective solution to the existing difficulties in dismantling ELVs. This approach can also provide guidelines in the design of automotive products. This paper illustrates the difficulty of handling polymers in dashboards. The physical properties of polymers prevent easy separation and recycling by using mechanical methods. Thus, dealers have to rely on chemical methods such as pyrolysis. Therefore, car designers should use a single material to benefit dealers. The use of materials for effective end-of-life processing without sacrificing the original performance requirements of the vehicle should be explored. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characteristics of organic matter in PM2.5 from an e-waste dismantling area in Taizhou, China.

PubMed

Gu, Zeping; Feng, Jialiang; Han, Wenliang; Wu, Minghong; Fu, Jiamo; Sheng, Guoying

2010-08-01

Solvent extractable organic compounds in PM(2.5) samples collected in Taizhou, a city famous for its electrical and electronic waste (e-waste) recycling industry in Zhejiang province of China, were analyzed to identify the main emission sources based on molecular markers. Two types of plastics which were most frequently contained in the e-wastes, wires/cables and plastic blocks, were burned in the lab and the particles emitted analyzed. The concentrations of PAHs and phthalate esters at the e-waste dismantling area during our sampling periods were about two times of that at the reference urban site, indicating the high pollution level there. The high concentrations of quaterphenyl found at the dismantling area indicated that burning of plastics or polymers was an important emission source of the PAHs in the fine particles. The diagnostic analysis based on the compositions of alkanes, hopanes and other molecular markers showed that engine exhaust, biomass burning and kitchen emissions were also important emission sources at the e-waste dismantling area. Our results suggested that more effort should be paid to control the correlative emission sources such as transportation and kitchen to achieve better air quality at the e-waste dismantling area besides regulating the recycling activities. Copyright 2010 Elsevier Ltd. All rights reserved.

Gap junction communications influence upon fibroblast synthesis of Type I collagen and fibronectin.

PubMed

Ehrlich, H Paul; Sun, Bonnie; Saggers, Gregory C; Kromath, Fatuma

2006-07-01

In rats polyvinyl alcohol sponge subcutaneous implants treated with gap junctional intercellular communications (GJIC) uncouplers showed reduced deposition of connective tissue. Do uncouplers inhibit the synthesis and deposition of a new connective tissue by fibroblasts? Confluent human dermal fibroblasts in serum-free medium received either endosulfan or oleamide, GJIC uncouplers. Collected media were subjected to Dot Blot analysis for native Type I collagen and fibronectin. Uncoupler-treated fibroblasts released less Type I collagen, while there was no change in fibronectin release. Collagen synthesis was restored to normal, when the uncouplers were removed, showing that these uncouplers were reversible and not toxic to cells. Northern blot analysis revealed procollagen alpha1 (I) mRNA was minimally affected by endosulfan. Oleamide-treated 17-day chick embryo calvaria explants were incubated with Type I collagen antibody, frozen, cryosectioned, and then subjected to rhodamine (Rh) tagged anti-mouse-IgG antibody, to detect newly deposited Type I collagen. Fluorescent antibody-collagen complexes were localized on the periphery of cells in control calvaria, but absent around cells in oleamide-treated calvaria. GJIC optimize collagen synthesis but not fibronectin synthesis. The lack of connective tissue deposited in granulation tissues treated with uncouplers appears related to the inhibition of collagen synthesis. These findings suggest that altering GJIC might control collagen deposition in scarring. 2006 Wiley-Liss, Inc.

Mitochondrial uncoupling agents antagonize rotenone actions in rat substantia nigra dopamine neurons.

PubMed

Wu, Yan-Na; Munhall, Adam C; Johnson, Steven W

2011-06-13

Mild uncoupling of oxidative phosphorylation has been reported to reduce generation of reactive oxygen species (ROS) and therefore may be neuroprotective. We reported previously that the mitochondrial poison rotenone enhanced currents evoked by N-methyl-D-aspartate (NMDA) by a ROS-dependent mechanism in rat midbrain dopamine neurons. Thus, rotenone, which produces a model of Parkinson's disease in rodents, may increase the risk of dopamine neuron excitotoxicity. The purpose of this study was to test the hypothesis that oxidative phosphorylation uncoupling agents would antagonize the effect of rotenone on NMDA current. We used patch pipettes to record whole-cell currents under voltage-clamp (-60 mV) in substantia nigra dopamine neurons in slices of rat brain. Rotenone, NMDA and uncoupling agents were added to the brain slice superfusate. Inward currents evoked by NMDA (30 μM) more than doubled in amplitude after slices were superfused for 30 min with 100 nM rotenone. Continuous superfusion with the uncoupling agent carbonyl cyanide-p-trifluoromethoxy-phenylhydrazone (1-3 nM) or 2,4-dinitrophenol (100 nM) significantly antagonized and delayed the ability of rotenone to potentiate NMDA currents. Coenzyme Q₁₀ (1-10 nM), which has been reported to facilitate uncoupling protein activity, also antagonized this action of rotenone. These results suggest that mild uncoupling of oxidative phosphorylation may protect dopamine neurons against injury from mitochondrial poisons such as rotenone. Published by Elsevier B.V.

Impaired adaptability of in vivo mitochondrial energetics to acute oxidative insult in aged skeletal muscle.

PubMed

Siegel, Michael P; Wilbur, Tim; Mathis, Mark; Shankland, Eric G; Trieu, Atlas; Harper, Mary-Ellen; Marcinek, David J

2012-01-01

Periods of elevated reactive oxygen species (ROS) production are a normal part of mitochondrial physiology. However, little is known about age-related changes in the mitochondrial response to elevated ROS in vivo. Significantly, ROS-induced uncoupling of oxidative phosphorylation has received attention as a negative feedback mechanism to reduce mitochondrial superoxide production. Here we use a novel in vivo spectroscopy system to test the hypothesis that ROS-induced uncoupling is diminished in aged mitochondria. This system simultaneously acquires (31)P magnetic resonance and near-infrared optical spectra to non-invasively measure phosphometabolite and O(2) concentrations in mouse skeletal muscle. Using low dose paraquat to elevate intracellular ROS we assess in vivo mitochondrial function in young, middle aged, and old mice. Oxidative phosphorylation was uncoupled to the same degree in response to ROS at each age, but this uncoupling was associated with loss of phosphorylation capacity and total ATP in old mice only. Using mice lacking UCP3 we demonstrate that this in vivo uncoupling is independent of this putative uncoupler of skeletal muscle mitochondria. These data indicate that ROS-induced uncoupling persists throughout life, but that oxidative stress leads to mitochondrial deficits and loss of ATP in aged organisms that may contribute to impaired function and degeneration. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Uncoupling of sgRNAs from their associated barcodes during PCR amplification of combinatorial CRISPR screens

PubMed Central

2018-01-01

Many implementations of pooled screens in mammalian cells rely on linking an element of interest to a barcode, with the latter subsequently quantitated by next generation sequencing. However, substantial uncoupling between these paired elements during lentiviral production has been reported, especially as the distance between elements increases. We detail that PCR amplification is another major source of uncoupling, and becomes more pronounced with increased amounts of DNA template molecules and PCR cycles. To lessen uncoupling in systems that use paired elements for detection, we recommend minimizing the distance between elements, using low and equal template DNA inputs for plasmid and genomic DNA during PCR, and minimizing the number of PCR cycles. We also present a vector design for conducting combinatorial CRISPR screens that enables accurate barcode-based detection with a single short sequencing read and minimal uncoupling. PMID:29799876

Cold Trap Dismantling and Sodium Removal at a Fast Breeder Reactor - 12327

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graf, A.; Petrick, H.; Stutz, U.

2012-07-01

The first German prototype Fast Breeder Nuclear Reactor (KNK) is currently being dismantled after being the only operating Fast Breeder-type reactor in Germany. As this reactor type used sodium as a coolant in its primary and secondary circuit, seven cold traps containing various amounts of partially activated sodium needed to be disposed of as part of the dismantling. The resulting combined difficulties of radioactive contamination and high chemical reactivity were handled by treating the cold traps differently depending on their size and the amount of sodium contained inside. Six small cold traps were processed onsite by cutting them up intomore » small parts using a band saw under a protective atmosphere. The sodium was then converted to sodium hydroxide by using water. The remaining large cold trap could not be handled in the same way due to its dimensions (2.9 m x 1.1 m) and the declared amount of sodium inside (1,700 kg). It was therefore manually dismantled inside a large box filled with a protective atmosphere, while the resulting pieces were packaged for later burning in a special facility. The experiences gained by KNK during this process may be advantageous for future dismantling projects in similar sodium-cooled reactors worldwide. The dismantling of a prototype fast breeder reactor provides the challenge not only to dismantle radioactive materials but also to handle sodium-contaminated or sodium-containing components. The treatment of sodium requires additional equipment and installations to ensure a safe handling. Since it is not permitted to bring sodium into a repository, all sodium has to be neutralized either through a controlled reaction with water or by incinerating. The resulting components can be disposed of as normal radioactive waste with no further conditions. The handling of sodium needs skilled and experienced workers to minimize the inherent risks. And the example of the disposal of the large KNK cold trap shows the interaction with others and also foreign decommissioning projects can provide solutions with were unknown before. (authors)« less

Low concentration of uncouplers of oxidative phosphorylation decreases the TNF-induced endothelial permeability and lethality in mice.

PubMed

Zakharova, Vlada V; Pletjushkina, Olga Yu; Galkin, Ivan I; Zinovkin, Roman A; Chernyak, Boris V; Krysko, Dmitri V; Bachert, Claus; Krysko, Olga; Skulachev, Vladimir P; Popova, Ekaterina N

2017-04-01

Mitochondrial dysfunctions occur in many diseases linked to the systemic inflammatory response syndrome (SIRS). Mild uncoupling of oxidative phosphorylation is known to rescue model animals from pathologies related to mitochondrial dysfunctions and overproduction of reactive oxygen species (ROS). To study the potential of SIRS therapy by uncoupling, we tested protonophore dinitrophenol (DNP) and a free fatty acid (FFA) anion carrier, lipophilic cation dodecyltriphenylphosphonium (C 12 TPP) in mice and in vitro models of SIRS. DNP and C 12 TPP prevented the body temperature drop and lethality in mice injected with high doses of a SIRS inducer, tumor necrosis factor (TNF). The mitochondria-targeted antioxidant plastoquinonyl decyltriphenylphosphonium (SkQ1) which also catalyzes FFA-dependent uncoupling revealed similar protective effects and downregulated expression of the NFκB-regulated genes (VCAM1, ICAM1, MCP1, and IL-6) involved in the inflammatory response of endothelium in aortas of the TNF-treated mice. In vitro mild uncoupling rescued from TNF-induced endothelial permeability, disassembly of cell contacts and VE-cadherin cleavage by the matrix metalloprotease 9 (ММР9). The uncouplers prevented TNF-induced expression of MMP9 via inhibition of NFκB signaling. Water-soluble antioxidant Trolox also prevented TNF-induced activation and permeability of endothelium in vitro via inhibition of NFκB signaling, suggesting that the protective action of the uncouplers is linked to their antioxidant potential. Copyright © 2017 Elsevier B.V. All rights reserved.

Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells.

PubMed

Stöckl, Petra; Zankl, Christina; Hütter, Eveline; Unterluggauer, Hermann; Laun, Peter; Heeren, Gino; Bogengruber, Edith; Herndler-Brandstetter, Dietmar; Breitenbach, Michael; Jansen-Dürr, Pidder

2007-09-15

The mitochondrial theory of aging predicts that functional alterations in mitochondria leading to reactive oxygen species (ROS) production contribute to the aging process in most if not all species. Using cellular senescence as a model for human aging, we have recently reported partial uncoupling of the respiratory chain in senescent human fibroblasts. In the present communication, we address a potential cause-effect relationship between impaired mitochondrial coupling and premature senescence. Chronic exposure of human fibroblasts to the chemical uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) led to a temporary, reversible uncoupling of oxidative phosphorylation. FCCP inhibited cell proliferation in a dose-dependent manner, and a significant proportion of the cells entered premature senescence within 12 days. Unexpectedly, chronic exposure of cells to FCCP led to a significant increase in ROS production, and the inhibitory effect of FCCP on cell proliferation was eliminated by the antioxidant N-acetyl-cysteine. However, antioxidant treatment did not prevent premature senescence, suggesting that a reduction in the level of oxidative phosphorylation contributes to phenotypical changes characteristic of senescent human fibroblasts. To assess whether this mechanism might be conserved in evolution, the influence of mitochondrial uncoupling on replicative life span of yeast cells was also addressed. Similar to our findings in human fibroblasts, partial uncoupling of oxidative phsophorylation in yeast cells led to a substantial decrease in the mother-cell-specific life span and a concomitant incrase in ROS, indicating that life span shortening by mild mitochondrial uncoupling may represent a "public" mechanism of aging.

A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal.

PubMed

Iwasaki, Hajime; Sasakawa, Tomoki; Takahoko, Kenichi; Takagi, Shunichi; Nakatsuka, Hideki; Suzuki, Takahiro; Iwasaki, Hiroshi

2016-06-01

We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

Pick-N-Pull Auto Dismantlers, Kansas City, LLC Inc. - Clean Water Act Public Notice

EPA Pesticide Factsheets

The EPA is providing notice of a proposed Administrative Penalty Assessment against Pick-N-Pull Auto Dismantlers, Kansas City, LLC, a subsidiary of Schnitzer Steel Industries, Inc., for alleged violations at its facilities at 8012 East Truman Rd., Kansas C

21 CFR 882.5810 - External functional neuromuscular stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional neuromuscular...

21 CFR 882.5810 - External functional neuromuscular stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional neuromuscular...

Using SAFRAN Software to Assess Radiological Hazards from Dismantling of Tammuz-2 Reactor Core at Al-tuwaitha Nuclear Site

NASA Astrophysics Data System (ADS)

Abed Gatea, Mezher; Ahmed, Anwar A.; jundee kadhum, Saad; Ali, Hasan Mohammed; Hussein Muheisn, Abbas

2018-05-01

The Safety Assessment Framework (SAFRAN) software has implemented here for radiological safety analysis; to verify that the dose acceptance criteria and safety goals are met with a high degree of confidence for dismantling of Tammuz-2 reactor core at Al-tuwaitha nuclear site. The activities characterizing, dismantling and packaging were practiced to manage the generated radioactive waste. Dose to the worker was considered an endpoint-scenario while dose to the public has neglected due to that Tammuz-2 facility is located in a restricted zone and 30m berm surrounded Al-tuwaitha site. Safety assessment for dismantling worker endpoint-scenario based on maximum external dose at component position level in the reactor pool and internal dose via airborne activity while, for characterizing and packaging worker endpoints scenarios have been done via external dose only because no evidence for airborne radioactivity hazards outside the reactor pool. The in-situ measurements approved that reactor core components are radiologically activated by Co-60 radioisotope. SAFRAN results showed that the maximum received dose for workers are (1.85, 0.64 and 1.3mSv/y) for activities dismantling, characterizing and packaging of reactor core components respectively. Hence, the radiological hazards remain below the low level hazard and within the acceptable annual dose for workers in radiation field

Complete nucleotide and derived amino acid sequence of cDNA encoding the mitochondrial uncoupling protein of rat brown adipose tissue: lack of a mitochondrial targeting presequence.

PubMed Central

Ridley, R G; Patel, H V; Gerber, G E; Morton, R C; Freeman, K B

1986-01-01

A cDNA clone spanning the entire amino acid sequence of the nuclear-encoded uncoupling protein of rat brown adipose tissue mitochondria has been isolated and sequenced. With the exception of the N-terminal methionine the deduced N-terminus of the newly synthesized uncoupling protein is identical to the N-terminal 30 amino acids of the native uncoupling protein as determined by protein sequencing. This proves that the protein contains no N-terminal mitochondrial targeting prepiece and that a targeting region must reside within the amino acid sequence of the mature protein. Images PMID:3012461

The Problem Child: Provocations toward Dismantling the Carceral State

ERIC Educational Resources Information Center

Meiners, Erica R.

2017-01-01

In this essay Erica R. Meiners argues that those committed to dismantling our nation's deep and racialized investments in policing and imprisoning must analyze how the flexible category of "the child," and its figurative powers, operate in complex ways to punish communities and naturalize and expand criminalization and surveillance.…

21 CFR 882.5860 - Implanted neuromuscular stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted neuromuscular stimulator. 882.5860... neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that provides electrical stimulation to a patient's peroneal or femoral nerve to cause muscles in the leg to contract, thus...

Hydroxynonenal and uncoupling proteins: a model for protection against oxidative damage.

PubMed

Echtay, Karim S; Pakay, Julian L; Esteves, Telma C; Brand, Martin D

2005-01-01

In this mini review we summarize recent studies from our laboratory that show the involvement of superoxide and the lipid peroxidation product 4-hydroxynonenal in the regulation of mitochondrial uncoupling. Superoxide produced during mitochondrial respiration is a major cause of the cellular oxidative damage that may underlie degenerative diseases and ageing. Superoxide production is very sensitive to the magnitude of the mitochondrial protonmotive force, so can be strongly decreased by mild uncoupling. Superoxide is able to give rise to other reactive oxygen species, which elicit deleterious effects primarily by oxidizing intracellular components, including lipids, DNA and proteins. Superoxide-induced lipid peroxidation leads to the production of reactive aldehydes, including 4-hydroxynonenal. These aldehydic lipid peroxidation products are in turn able to modify proteins such as mitochondrial uncoupling proteins and the adenine nucleotide translocase, converting them into active proton transporters. This activation induces mild uncoupling and so diminishes mitochondrial superoxide production, hence protecting against disease and oxidative damage at the expense of energy production.

Transcriptomic and macroevolutionary evidence for phenotypic uncoupling between frog life history phases

PubMed Central

Wollenberg Valero, Katharina C.; Garcia-Porta, Joan; Rodríguez, Ariel; Arias, Mónica; Shah, Abhijeet; Randrianiaina, Roger Daniel; Brown, Jason L.; Glaw, Frank; Amat, Felix; Künzel, Sven; Metzler, Dirk; Isokpehi, Raphael D.; Vences, Miguel

2017-01-01

Anuran amphibians undergo major morphological transitions during development, but the contribution of their markedly different life-history phases to macroevolution has rarely been analysed. Here we generate testable predictions for coupling versus uncoupling of phenotypic evolution of tadpole and adult life-history phases, and for the underlying expression of genes related to morphological feature formation. We test these predictions by combining evidence from gene expression in two distantly related frogs, Xenopus laevis and Mantidactylus betsileanus, with patterns of morphological evolution in the entire radiation of Madagascan mantellid frogs. Genes linked to morphological structure formation are expressed in a highly phase-specific pattern, suggesting uncoupling of phenotypic evolution across life-history phases. This gene expression pattern agrees with uncoupled rates of trait evolution among life-history phases in the mantellids, which we show to have undergone an adaptive radiation. Our results validate a prevalence of uncoupling in the evolution of tadpole and adult phenotypes of frogs. PMID:28504275

Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

PubMed

Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

2014-08-01

Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, p<0.001, sr(2)=0.32). Together, these predictors accounted for 65% of variance in disability (R(2)=0.65 p<0.001). The current investigation revealed that neuromuscular adaptations are independent from clinical pain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations. Copyright © 2014 Elsevier Ltd. All rights reserved.

eNOS-uncoupling in age-related erectile dysfunction

PubMed Central

Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

2011-01-01

Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

Oxidative phosphorylation in Debaryomyces hansenii: physiological uncoupling at different growth phases.

PubMed

Cabrera-Orefice, Alfredo; Guerrero-Castillo, Sergio; Díaz-Ruíz, Rodrigo; Uribe-Carvajal, Salvador

2014-07-01

Physiological uncoupling of mitochondrial oxidative phosphorylation (OxPhos) was studied in Debaryomyces hansenii. In other species, such as Yarrowia lipolytica and Saccharomyces cerevisiae, OxPhos can be uncoupled through differential expression of branched respiratory chain enzymes or by opening of a mitochondrial unspecific channel (ScMUC), respectively. However D. hansenii mitochondria, which contain both a branched respiratory chain and a mitochondrial unspecific channel (DhMUC), selectively uncouple complex I-dependent rate of oxygen consumption in the stationary growth phase. The uncoupled complex I-dependent respiration was only 20% of the original activity. Inhibition was not due to inactivation of complex I, lack of protein expression or to differential expression of alternative oxidoreductases. Furthermore, all other respiratory chain activities were normal. Decrease of complex I-dependent respiration was due to NAD(+) loss from the matrix, probably through an open of DhMUC. When NAD(+) was added back, coupled complex I-activity was recovered. NAD(+) re-uptake was independent of DhMUC opening and seemed to be catalyzed by a NAD(+)-specific transporter, which was sensitive to bathophenanthroline, bromocresol purple or pyridoxal-5'-phosphate as described for S. cerevisiae mitochondrial NAD(+) transporters. Loss of NAD(+) from the matrix through an open MUC is proposed as an additional mechanism to uncouple OxPhos. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Physiological uncoupling of mitochondrial oxidative phosphorylation. Studies in different yeast species.

PubMed

Guerrero-Castillo, Sergio; Araiza-Olivera, Daniela; Cabrera-Orefice, Alfredo; Espinasa-Jaramillo, Juan; Gutiérrez-Aguilar, Manuel; Luévano-Martínez, Luís A; Zepeda-Bastida, Armando; Uribe-Carvajal, Salvador

2011-06-01

Under non-phosphorylating conditions a high proton transmembrane gradient inhibits the rate of oxygen consumption mediated by the mitochondrial respiratory chain (state IV). Slow electron transit leads to production of reactive oxygen species (ROS) capable of participating in deleterious side reactions. In order to avoid overproducing ROS, mitochondria maintain a high rate of O(2) consumption by activating different exquisitely controlled uncoupling pathways. Different yeast species possess one or more uncoupling systems that work through one of two possible mechanisms: i) Proton sinks and ii) Non-pumping redox enzymes. Proton sinks are exemplified by mitochondrial unspecific channels (MUC) and by uncoupling proteins (UCP). Saccharomyces. cerevisiae and Debaryomyces hansenii express highly regulated MUCs. Also, a UCP was described in Yarrowia lipolytica which promotes uncoupled O(2) consumption. Non-pumping alternative oxido-reductases may substitute for a pump, as in S. cerevisiae or may coexist with a complete set of pumps as in the branched respiratory chains from Y. lipolytica or D. hansenii. In addition, pumps may suffer intrinsic uncoupling (slipping). Promising models for study are unicellular parasites which can turn off their aerobic metabolism completely. The variety of energy dissipating systems in eukaryote species is probably designed to control ROS production in the different environments where each species lives.

Triclosan is a Mitochondrial Uncoupler in Live Zebrafish

PubMed Central

Shim, Juyoung; Weatherly, Lisa M.; Luc, Richard H.; Dorman, Maxwell T.; Neilson, Andy; Ng, Ryan; Kim, Carol H.; Millard, Paul J.; Gosse, Julie A.

2016-01-01

Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24 hour post fertilization zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XFe 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, following acute exposure to TCS, basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96 well assay format. The method developed in this study provides a high-throughput tool to identify previously-unknown mitochondrial uncouplers in a living organism. PMID:27111768

UCP1, the mitochondrial uncoupling protein of brown adipocyte: A personal contribution and a historical perspective.

PubMed

Ricquier, Daniel

2017-03-01

The present text summarizes what was my contribution, starting in 1975, to the research on the uncoupling protein 1 (UCP1), the mitochondrial uncoupler of brown adipocytes. The research on UCP1 aimed at identifying the mechanisms of heat production by brown adipocytes that occurs in mammals either at birth or during cold exposure and arousal in hibernators. With others and in particular Dr. David Nicholls, I participated in the first experiments that contributed to the identification of UCP1. Important steps were the obtention of UCP1 antibodies followed with my main collaborator and friend Frédéric Bouillaud with the initial cloning of the UCP1 cDNA and gene from rats and humans. These molecular tools were then used not only to analyse UCP1 uncoupling activity and to investigate the effects of mutagenesis on the uncoupling function of this protein, but also to decipher the transcriptional regulation of the UCP1 gene. In addition to experiments carried out in rodents, we could identify UCP1 and thermogenic brown adipocytes in humans. A more recent outcome of our research on this uncoupling protein was the identification of a second isoform of UCP, that we named UCP2, and of several UCP homologues in mammals, chicken and plants. UCP1 is certainly a unique mitochondrial transporter able to uncouple respiration from ADP phosphorylation in mitochondria. The discovery of this protein has opened new avenues for studying energy expenditure in relation to overweight, obesity and related pathologies. Copyright © 2016. Published by Elsevier B.V.

Alkyl-substituted phenylamino derivatives of 7-nitrobenz-2-oxa-1,3-diazole as uncouplers of oxidative phosphorylation and antibacterial agents: involvement of membrane proteins in the uncoupling action.

PubMed

Antonenko, Yuri N; Denisov, Stepan S; Khailova, Ljudmila S; Nazarov, Pavel A; Rokitskaya, Tatyana; Tashlitsky, Vadim N; Firsov, Alexander M; Korshunova, Galina A; Kotova, Elena A

2017-03-01

In search for new effective uncouplers of oxidative phosphorylation, we studied 4-aryl amino derivatives of a fluorescent group 7-nitrobenz-2-oxa-1,3-diazol (NBD). In our recent work (Denisov et al., Bioelectrochemistry, 2014), NBD-conjugated alkyl amines (NBD-C n ) were shown to exhibit uncoupling activity. It was concluded that despite a pK a value being about 10, the expected hindering of the uncoupling activity could be overcome by insertion of an alkyl chain. There is evidence in the literature that the introduction of an aryl substituent in the 4-amino NBD group shifts the pK a to neutral values. Here we report the data on the properties of a number of 4-arylamino derivatives of NBD, namely, alkylphenyl-amino-NBD (C n -phenyl-NBD) with varying alkyl chain C n . By measuring the electrical current across planar bilayer lipid membrane, the protonophoric activity of C n -phenyl-NBD at neutral pH grew monotonously from C 1 - to C 6 -phenyl-NBD. All of these compounds increased the respiration rate and reduced the membrane potential of isolated rat liver mitochondria. Importantly, the uncoupling action of C 6 - and C 4 -phenyl-NBD was partially reversed by glutamate, diethyl pyrocarbonate (DEPC), 6-ketocholestanol, and carboxyatractyloside, thus pointing to the involvement of membrane proteins in the uncoupling activity of C n -phenyl-NBD in mitochondria. The pronounced recoupling effect of DEPC, an inhibitor of an aspartate-glutamate carrier (AGC), and that of its substrates for the first time highlighted AGC participation in the action of potent uncouplers on mitochondria. C 6 -phenyl-NBD produced strong antimicrobial effect on Bacillus subtilis, which manifested itself in cell membrane depolarization and suppression of bacterial growth at submicromolar concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Polybrominated diphenyl ethers in the atmosphere of Taizhou, a major e-waste dismantling area in China.

PubMed

Han, Wenliang; Feng, Jialiang; Gu, Zeping; Chen, Duohong; Wu, Minghong; Fu, Jiamo

2009-12-01

Concentrations, congener profiles, gas-particle partitioning and size distributions of polybrominated diphenyl ethers (PBDEs) in the atmosphere of Taizhou were studied to evaluate the impact of e-waste recycling on the environment. Total concentration of 13 PBDEs near the e-waste dismantling area was 506 pg m(-3) in summer and 1,662 pg m(-3) in winter, about 7 times higher than that of the reference urban site, but much lower than that of Guiyu, another major e-waste dismantling area in China. This should be attributable to the centralized management measures taken in recent years in Taizhou. BDE-209 was the major congener and mainly in coarse particles.

Sugammadex: A Review of Neuromuscular Blockade Reversal.

PubMed

Keating, Gillian M

2016-07-01

Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade.

2015 AERA Presidential Address: Morally Engaged Research/ers Dismantling Epistemological Nihilation in the Age of Impunity

ERIC Educational Resources Information Center

King, Joyce E.

2017-01-01

This article presents Joyce E. King's 2015 AERA presidential address, which artfully combined scholarly discourse with performance elements and diverse voices in several multimedia formats. In discussing morally engaged research/ers dismantling epistemological nihilation, the article advances the argument that the moral stance, solidarity with…

Developing the Teaching Material Using ATV Cooperated with Student on Manufacturing Practice

NASA Astrophysics Data System (ADS)

Tsukamoto, Kimihide; Yamamoto, Keiichiro; Ueno, Takayuki; Imazato, Tatsunari; Sakamoto, Hidetoshi

Recently, a number of students have entered the college of technology with no experience of dismantling and assembling of even an easy machine (including toys) . It is necessary to study the correct usage of tools for lower grade students as a base of the technical education for dismantling and assembling of the machine. However, enough understanding has not been obtained though the usage of the tool is trained for first grade students. So, we executed the development on the teaching text and material of student practice curriculum, which is attractive subject of all-terrain vehicle [ATV]‧s dismantling and assembling for lower grade students. This practice make the student learn both how to use the tools and the steer mechanism of car through the dismantling and assembling of ATV. The text book and sub-teaching materials of this practice curriculum were created in cooperation with fifth grade students as graduation research. As a result, an effective teaching and learning text and sub-teaching materials in manufacturing practice could be developed from student‧s point of view.

Uncoupling Protein 2 and Metabolic Diseases

PubMed Central

Sreedhar, Annapoorna; Zhao, Yunfeng

2017-01-01

Mitochondria are fascinating organelles involved in various cellular-metabolic activities that are integral for mammalian development. Although they perform diverse, yet interconnected functions, mitochondria are remarkably regulated by complex signaling networks. Therefore, it is not surprising that mitochondrial dysfunction is involved in plethora of diseases, including neurodegenerative and metabolic disorders. One of the many factors that lead to mitochondrial-associated metabolic diseases is the uncoupling protein-2, a family of mitochondrial anion proteins present in the inner mitochondrial membrane. Since their discovery, uncoupling proteins have attracted considerable attention due to their involvement in mitochondrial-mediated oxidative stress and energy metabolism. This review attempts to provide a summary of recent developments in the field of uncoupling protein 2 relating to mitochondrial associated metabolic diseases. PMID:28351676

UCP4C mediates uncoupled respiration in larvae of Drosophila melanogaster.

PubMed

Da-Ré, Caterina; De Pittà, Cristiano; Zordan, Mauro A; Teza, Giordano; Nestola, Fabrizio; Zeviani, Massimo; Costa, Rodolfo; Bernardi, Paolo

2014-05-01

Larvae of Drosophila melanogaster reared at 23°C and switched to 14°C for 1 h are 0.5°C warmer than the surrounding medium. In keeping with dissipation of energy, respiration of Drosophila melanogaster larvae cannot be decreased by the F-ATPase inhibitor oligomycin or stimulated by protonophore. Silencing of Ucp4C conferred sensitivity of respiration to oligomycin and uncoupler, and prevented larva-to-adult progression at 15°C but not 23°C. Uncoupled respiration of larval mitochondria required palmitate, was dependent on Ucp4C and was inhibited by guanosine diphosphate. UCP4C is required for development through the prepupal stages at low temperatures and may be an uncoupling protein.

The conceptual solutions concerning decommissioning and dismantling of Russian civil nuclear powered ships

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulikov, Konstantin N.; Nizamutdinov, Rinat A.; Abramov, Andrey N.

From 1959 up to 1991 nine civil nuclear powered ships were built in Russia: eight ice-breakers and one lash lighter carrier (cargo ship). At the present time three of them were taking out of service: ice-breaker 'Lenin' is decommissioned as a museum and is set for storage in the port of Murmansk, nuclear ice-breakers 'Arktika' and 'Sibir' are berthing. The ice-breakers carrying rad-wastes appear to be a possible source of radiation contamination of Murmansk region and Kola Bay because the ship long-term storage afloat has the negative effect on hull's structures. As the result of this under the auspices ofmore » the Federal Targeted Program 'Nuclear and Radiation Safety of Russia for 2008 and the period until 2015' the conception and projects of decommissioning of nuclear-powered ships are developed by the State corporation Rosatom with the involvement of companies of United Shipbuilding Corporation. In developing the principal provisions of conception of decommissioning and dismantling of icebreakers the technical and economic assessment of dismantling options in ship-repairing enterprises of North-West of Russia was performed. The paper contains description of options, research procedure, analysis of options of decommissioning and dismantling of nuclear ice-breakers, taking into account the principle of optimization of potential radioactive effect to personnel, human population and environment. The report's conclusions contain the recommendations for selection of option for development of nuclear icebreaker decommissioning and dismantling projects. (authors)« less

Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension.

PubMed

Papazova, Diana A; Friederich-Persson, Malou; Joles, Jaap A; Verhaar, Marianne C

2015-01-01

Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (Po2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney hypoxia. Lewis rats underwent syngenic renal transplantation (TX) and contralateral nephrectomy. Controls were uninephrectomized (1K-CON) or left untreated (2K-CON). After 7 days, urinary excretion of protein and thiobarbituric acid-reactive substances were measured, and after 14 days glomerular filtration rate (GFR), renal blood flow, whole kidney Qo2, cortical Po2, kidney cortex mitochondrial uncoupling, renal oxidative damage, and tubulointerstitial injury were assessed. TX, compared with 1K-CON, resulted in mitochondrial uncoupling mediated via uncoupling protein-2 (16 ± 3.3 vs. 0.9 ± 0.4 pmol O2 · s(-1)· mg protein(-1), P < 0.05) and increased whole kidney Qo2 (55 ± 16 vs. 33 ± 10 μmol O2/min, P < 0.05). Corticomedullary Po2 was lower in TX compared with 1K-CON (30 ± 13 vs. 47 ± 4 μM, P < 0.05) whereas no significant difference was observed between 2K-CON and 1K-CON rats. Proteinuria, oxidative damage, and the tubulointerstitial injury score were not significantly different in 1K-CON and TX. Treatment of donors for 5 days with mito-TEMPO reduced mitochondrial uncoupling but did not affect renal hemodynamics, Qo2, Po2, or injury. Collectively, our results demonstrate increased mitochondrial uncoupling as an early event after experimental renal transplantation associated with increased oxygen consumption and kidney hypoxia in the absence of increases in markers of damage. Copyright © 2015 the American Physiological Society.

Free fatty acids as inducers and regulators of uncoupling of oxidative phosphorylation in liver mitochondria with participation of ADP/ATP- and aspartate/glutamate-antiporter.

PubMed

Samartsev, V N; Marchik, E I; Shamagulova, L V

2011-02-01

In liver mitochondria fatty acids act as protonophoric uncouplers mainly with participation of internal membrane protein carriers - ADP/ATP and aspartate/glutamate antiporters. In this study the values of recoupling effects of carboxyatractylate and glutamate (or aspartate) were used to assess the degree of participation of ADP/ATP and aspartate/glutamate antiporters in uncoupling activity of fatty acids. These values were determined from the ability of these recoupling agents to suppress the respiration stimulated by fatty acids and to raise the membrane potential reduced by fatty acids. Increase in palmitic and lauric acid concentration was shown to increase the degree of participation of ADP/ATP antiporter and to decrease the degree of participation of aspartate/glutamate antiporter in uncoupling to the same extent. These data suggest that fatty acids are not only inducers of uncoupling of oxidative phosphorylation, but that they also act the regulators of this process. The linear dependence of carboxyatractylate and glutamate recoupling effects ratio on palmitic and lauric acids concentration was established. Comparison of the effects of fatty acids (palmitic, myristic, lauric, capric, and caprylic having 16, 14, 12, 10, and 8 carbon atoms, respectively) has shown that, as the hydrophobicity of fatty acids decreases, the effectiveness decreases to a greater degree than the respective values of their specific uncoupling activity. The action of fatty acids as regulators of uncoupling is supposed to consist of activation of transport of their anions from the internal to the external monolayer of the internal membrane with participation of ADP/ATP antiporter and, at the same time, in inhibition of this process with the participation of aspartate/glutamate antiporter.

Asiatic acid uncouples respiration in isolated mouse liver mitochondria and induces HepG2 cells death.

PubMed

Lu, Yapeng; Liu, Siyuan; Wang, Ying; Wang, Dang; Gao, Jing; Zhu, Li

2016-09-05

Asiatic acid, one of the triterpenoid components isolated from Centella asiatica, has received increasing attention due to a wide variety of biological activities. To date, little is known about its mechanisms of action. Here we examined the cytotoxic effect of asiatic acid on HepG2 cells and elucidated some of the underlying mechanisms. Asiatic acid induced rapid cell death, as well as mitochondrial membrane potential (MMP) dissipation, ATP depletion and cytochrome c release from mitochondria to the cytosol in HepG2 cells. In mitochondria isolated from mouse liver, asiatic acid treatment significantly stimulated the succinate-supported state 4 respiration rate, dissipated the MMP, increased Ca(2+) release from Ca(2+)-loaded mitochondria, decreased ATP content and promoted cytochrome c release, indicating the uncoupling effect of asiatic acid. Hydrogen peroxide (H2O2) produced by succinate-supported mitochondrial respiration was also significantly inhibited by asiatic acid. In addition, asiatic acid inhibited Ca(2+)-induced mitochondrial swelling but did not induce mitochondrial swelling in hyposmotic potassium acetate medium which suggested that asiatic acid may not act as a protonophoric uncoupler. Inhibition of uncoupling proteins (UCPs) or blockade of adenine nucleotide transporter (ANT) attenuated the effect of asiatic acid on MMP dissipation, Ca(2+) release, mitochondrial respiration and HepG2 cell death. When combined inhibition of UCPs and ANT, asiatic acid-mediated uncoupling effect was noticeably alleviated. These results suggested that both UCPs and ANT partially contribute to the uncoupling properties of asiatic acid. In conclusion, asiatic acid is a novel mitochondrial uncoupler and this property is potentially involved in its toxicity on HepG2 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibitors of V-ATPase proton transport reveal uncoupling functions of tether linking cytosolic and membrane domains of V0 subunit a (Vph1p).

PubMed

Chan, Chun-Yuan; Prudom, Catherine; Raines, Summer M; Charkhzarrin, Sahba; Melman, Sandra D; De Haro, Leyma P; Allen, Chris; Lee, Samuel A; Sklar, Larry A; Parra, Karlett J

2012-03-23

Vacuolar ATPases (V-ATPases) are important for many cellular processes, as they regulate pH by pumping cytosolic protons into intracellular organelles. The cytoplasm is acidified when V-ATPase is inhibited; thus we conducted a high-throughput screen of a chemical library to search for compounds that acidify the yeast cytosol in vivo using pHluorin-based flow cytometry. Two inhibitors, alexidine dihydrochloride (EC(50) = 39 μM) and thonzonium bromide (EC(50) = 69 μM), prevented ATP-dependent proton transport in purified vacuolar membranes. They acidified the yeast cytosol and caused pH-sensitive growth defects typical of V-ATPase mutants (vma phenotype). At concentrations greater than 10 μM the inhibitors were cytotoxic, even at the permissive pH (pH 5.0). Membrane fractions treated with alexidine dihydrochloride and thonzonium bromide fully retained concanamycin A-sensitive ATPase activity despite the fact that proton translocation was inhibited by 80-90%, indicating that V-ATPases were uncoupled. Mutant V-ATPase membranes lacking residues 362-407 of the tether of Vph1p subunit a of V(0) were resistant to thonzonium bromide but not to alexidine dihydrochloride, suggesting that this conserved sequence confers uncoupling potential to V(1)V(0) complexes and that alexidine dihydrochloride uncouples the enzyme by a different mechanism. The inhibitors also uncoupled the Candida albicans enzyme and prevented cell growth, showing further specificity for V-ATPases. Thus, a new class of V-ATPase inhibitors (uncouplers), which are not simply ionophores, provided new insights into the enzyme mechanism and original evidence supporting the hypothesis that V-ATPases may not be optimally coupled in vivo. The consequences of uncoupling V-ATPases in vivo as potential drug targets are discussed.

Effect of ethanol on the palmitate-induced uncoupling of oxidative phosphorylation in liver mitochondria.

PubMed

Samartsev, V N; Belosludtsev, K N; Chezganova, S A; Zeldi, I P

2002-11-01

The effect of ethanol on the uncoupling activity of palmitate and recoupling activities of carboxyatractylate and glutamate was studied in liver mitochondria at various Mg2+ concentrations and medium pH values (7.0, 7.4, and 7.8). Ethanol taken at concentration of 0.25 M had no effect on the uncoupling activity of palmitic acid in the presence of 2 mM MgCl2 and decreased the recoupling effects of carboxyatractylate and glutamate added to mitochondria either just before or after the fatty acid. However, ethanol did not modify the overall recoupling effect of carboxyatractylate and glutamate taken in combination. The effect of ethanol decreased as medium pH was decreased to 7.0. Elevated concentration of Mg2+ (up to 8 mM) inhibits the uncoupling effect of palmitate. Ethanol eliminates substantially the recoupling effect of Mg2+ under these conditions, but does not influence the recoupling effects of carboxyatractylate and glutamate. It is inferred that ADP/ATP and aspartate/glutamate antiporters are involved in uncoupling function as single uncoupling complex with the common fatty acid pool. Fatty acid molecules gain the ability to migrate under the action of ethanol: from ADP/ATP antiporter to aspartate/glutamate antiporter on addition of carboxyatractylate and in opposite direction on addition of glutamate. Possible mechanisms of fatty acid translocation from one transporter to another are discussed.

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat.

PubMed

Somasundaram, S; Sigthorsson, G; Simpson, R J; Watts, J; Jacob, M; Tavares, I A; Rafi, S; Roseth, A; Foster, R; Price, A B; Wrigglesworth, J M; Bjarnason, I

2000-05-01

The pathogenesis of NSAID-induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation. To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat. We compared key pathophysiologic events in the small bowel following (i) dinitrophenol, an uncoupling agent (ii) parenteral aspirin, to inhibit cyclooxygenase without causing a 'topical' effect and (iii) the two together, using (iv) indomethacin as a positive control. Dinitrophenol altered intestinal mitochondrial morphology, increased intestinal permeability and caused inflammation without affecting gastric permeability or intestinal prostanoid levels. Parenteral aspirin decreased mucosal prostanoids without affecting intestinal mitochondria in vivo, gastric or intestinal permeability. Aspirin caused no inflammation or ulcers. When dinitrophenol and aspirin were given together the changes in intestinal mitochondrial morphology, permeability, inflammation and prostanoid levels and the macro- and microscopic appearances of intestinal ulcers were similar to indomethacin. These studies allow dissociation of the contribution and consequences of uncoupling of mitochondrial oxidative phosphorylation and cyclooxygenase inhibition in the pathophysiology of NSAID enteropathy. While uncoupling of enterocyte mitochondrial oxidative phosphorylation leads to increased intestinal permeability and low grade inflammation, concurrent decreases in mucosal prostanoids appear to be important in the development of ulcers.

The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) uncouples mitochondrial oxidative phosphorylation in both sea lamprey (Petromyzon marinus) and TFM-tolerant rainbow trout (Oncorhynchus mykiss).

PubMed

Birceanu, Oana; McClelland, Grant B; Wang, Yuxiang S; Brown, Jason C L; Wilkie, Michael P

2011-04-01

The toxicity of 3-trifluoromethyl-4-nitrophenol (TFM) appears to be due to a mismatch between ATP supply and demand in lamprey, depleting glycogen stores and starving the nervous system of ATP. The cause of this TFM-induced ATP deficit is unclear. One possibility is that TFM uncouples mitochondrial oxidative phosphorylation, thus impairing ATP production. To test this hypothesis, mitochondria were isolated from the livers of sea lamprey and rainbow trout, and O(2) consumption rates were measured in the presence of TFM or 2,4-dinitrophenol (2,4-DNP), a known uncoupler of oxidative phosphorylation. TFM and 2,4-DNP markedly increased State IV respiration in a dose-dependent fashion, but had no effect on State III respiration, which is consistent with uncoupling of oxidative phosphorylation. To determine how TFM uncoupled oxidative phosphorylation, the mitochondrial transmembrane potential (TMP) was recorded using the mitochondria-specific dye rhodamine 123. Mitochondrial TMP decreased by 22% in sea lamprey, and by 28% in trout following treatment with 50μmolL(-1) TFM. These findings suggest that TFM acted as a protonophore, dissipating the proton motive force needed to drive ATP synthesis. We conclude that the mode of TFM toxicity in sea lamprey and rainbow trout is via uncoupling of oxidative phosphorylation, leading to impaired ATP production. Copyright © 2010 Elsevier Inc. All rights reserved.

Triclosan is a mitochondrial uncoupler in live zebrafish.

PubMed

Shim, Juyoung; Weatherly, Lisa M; Luc, Richard H; Dorman, Maxwell T; Neilson, Andy; Ng, Ryan; Kim, Carol H; Millard, Paul J; Gosse, Julie A

2016-12-01

Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here, we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24-hour post-fertilization (hpf) zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XF e 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, after acute exposure to TCS, the basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96-well assay format. The method developed in this study provides a high-throughput tool to identify previously unknown mitochondrial uncouplers in a living organism. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Uncoupling of oxidative phosphorylation by curcumin: implication of its cellular mechanism of action.

PubMed

Lim, Han Wern; Lim, Hwee Ying; Wong, Kim Ping

2009-11-06

Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F(0)F(1)-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 microM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F(0)F(1)-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

Uncoupling Mitochondrial Respiration for Diabesity.

PubMed

Larrick, James W; Larrick, Jasmine W; Mendelsohn, Andrew R

2016-08-01

Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity.

Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Han Wern; Lim, Hwee Ying; Wong, Kim Ping, E-mail: bchsitkp@nus.edu.sg

2009-11-06

Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F{sub 0}F{sub 1}-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 {mu}M, curcumin was found to inhibit mitochondrial respiration which is a characteristic featuremore » of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F{sub 0}F{sub 1}-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.« less

29 CFR (non - mandatory) Appendix D to Subpart L of Part 1926-List of Training Topics for Scaffold Erectors and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Training Topics for Scaffold Erectors and Dismantlers (Non Labor Regulations Relating to Labor (Continued... 1926—List of Training Topics for Scaffold Erectors and Dismantlers This Appendix D is provided to serve... be trained in the following topics: • General Overview of Scaffolding • regulations and standards...

Dismantling the School Sport Partnership Infrastructure: Findings from a Survey of Physical Education and School Sport Practitioners

ERIC Educational Resources Information Center

Mackintosh, Chris

2014-01-01

This research examines the perceptions of education practitioners to the proposed changes to the school sport partnership (SSP) programme in England and in particular its implications for primary school physical education. It aims to explore insights into the dismantling of this partnership programme. The SSP system developed club links, increased…

The effects of neuromuscular training on knee joint motor control during sidecutting in female elite soccer and handball players.

PubMed

Zebis, Mette K; Bencke, Jesper; Andersen, Lars L; Døssing, Simon; Alkjaer, Tine; Magnusson, S Peter; Kjaer, Michael; Aagaard, Per

2008-07-01

The project aimed to implement neuromuscular training during a full soccer and handball league season and to experimentally analyze the neuromuscular adaptation mechanisms elicited by this training during a standardized sidecutting maneuver known to be associated with non-contact anterior cruciate ligament (ACL) injury. The players were tested before and after 1 season without implementation of the prophylactic training and subsequently before and after a full season with the implementation of prophylactic training. A total of 12 female elite soccer players and 8 female elite team handball players aged 26 +/- 3 years at the start of the study. The subjects participated in a specific neuromuscular training program previously shown to reduce non-contact ACL injury. Neuromuscular activity at the knee joint, joint angles at the hip and knee, and ground reaction forces were recorded during a sidecutting maneuver. Neuromuscular activity in the prelanding phase was obtained 10 and 50 ms before foot strike on a force plate and at 10 and 50 ms after foot strike on a force plate. Neuromuscular training markedly increased before activity and landing activity electromyography (EMG) of the semitendinosus (P < 0.05), while quadriceps EMG activity remained unchanged. Neuromuscular training increased EMG activity for the medial hamstring muscles, thereby decreasing the risk of dynamic valgus. This observed neuromuscular adaptation during sidecutting could potentially reduce the risk for non-contact ACL injury.

Uncoupling nicotine mediated motoneuron axonal pathfinding errors and muscle degeneration in zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welsh, Lillian; Tanguay, Robert L.; Svoboda, Kurt R.

Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development and that their axons made pathfinding errors (Svoboda, K.R., Vijayaraghaven, S., Tanguay, R.L., 2002. Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J. Neurosci. 22, 10731-10741). In that study, we did not consider the potential role that altered skeletalmore » muscle development caused by nicotine exposure could play in contributing to the errors in spinal motoneuron axon pathfinding. In this study, we show that an alteration in skeletal muscle development occurs in tandem with alterations in spinal motoneuron development upon exposure to nicotine. The alteration in the muscle involves the binding of nicotine to the muscle-specific AChRs. The nicotine-induced alteration in muscle development does not occur in the zebrafish mutant (sofa potato, [sop]), which lacks muscle-specific AChRs. Even though muscle development is unaffected by nicotine exposure in sop mutants, motoneuron axonal pathfinding errors still occur in these mutants, indicating a direct effect of nicotine exposure on nervous system development.« less

Effects of nitric oxide on neuromuscular properties of developing zebrafish embryos.

PubMed

Jay, Michael; Bradley, Sophie; McDearmid, Jonathan Robert

2014-01-01

Nitric oxide is a bioactive signalling molecule that is known to affect a wide range of neurodevelopmental processes. However, its functional relevance to neuromuscular development is not fully understood. Here we have examined developmental roles of nitric oxide during formation and maturation of neuromuscular contacts in zebrafish. Using histochemical approaches we show that elevating nitric oxide levels reduces the number of neuromuscular synapses within the axial swimming muscles whilst inhibition of nitric oxide biosynthesis has the opposite effect. We further show that nitric oxide signalling does not change synapse density, suggesting that the observed effects are a consequence of previously reported changes in motor axon branch formation. Moreover, we have used in vivo patch clamp electrophysiology to examine the effects of nitric oxide on physiological maturation of zebrafish neuromuscular junctions. We show that developmental exposure to nitric oxide affects the kinetics of spontaneous miniature end plate currents and impacts the neuromuscular drive for locomotion. Taken together, our findings implicate nitrergic signalling in the regulation of zebrafish neuromuscular development and locomotor maturation.

Burn after feeding. An old uncoupler of oxidative phosphorylation is redesigned for the treatment of nonalcoholic fatty liver disease.

PubMed

Fromenty, B

2014-10-01

Uncoupling of oxidative phosphorylation (OXPHOS) in brown adipose tissue can be used by hibernating animals to produce heat at the expense of their fat mass. In a recent work, Dr Shulman et al. generated a liver-targeted derivative of the prototypical OXPHOS uncoupler 2,4-dinitrophenol that alleviated steatosis, hypertriglyceridemia and insulin resistance in several models of nonalcoholic fatty liver disease and type 2 diabetes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: A comparative prospective clinical trial.

PubMed

de Souza, Camila M; Tardelli, Maria A; Tedesco, Helio; Garcia, Natalia N; Caparros, Mario P; Alvarez-Gomez, Jose A; de Oliveira Junior, Itamar S

2015-10-01

Renal failure affects the pharmacology of nondepolarizing neuromuscular blockers making recovery of neuromuscular function unpredictable. Sugammadex antagonises rocuronium-induced neuromuscular blockade by encapsulating rocuronium, creating a stable complex molecule that is mainly excreted by the kidneys. Previous studies suggest that sugammadex is effective in reversing moderate neuromuscular block in the presence of renal failure, but no data are available regarding reversal of profound neuromuscular block in patients with renal failure. The objective of this study is to compare the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in patients with end-stage renal disease and those with normal renal function. A prospective clinical trial. Two university hospitals, from 1 October 2011 to 31 January 2012. Forty patients undergoing kidney transplant: 20 with renal failure [creatinine clearance (ClCr) <30 ml min] and 20 control patients (ClCr >90 ml min). Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) stimulation. Profound neuromuscular block (posttetanic count, one to three responses) was maintained during surgery. Sugammadex 4 mg kg was administered on completion of skin closure. Recovery of the TOF ratio to 0.9 was recorded. Monitoring of neuromuscular function continued in the postanesthesia care unit for a further 2 h. The efficacy of sugammadex was evaluated by the time taken for the TOF ratio to recover to 0.9. The safety of sugammadex was assessed by monitoring for recurrence of neuromuscular block every 15 min for 2 h. Secondary variables were time to recovery of TOF ratio to 0.7 and 0.8. After sugammadex administration, the mean time for recovery of the TOF ratio to 0.9 was prolonged in the renal failure group (5.6 ± 3.6 min) compared with the control group (2.7 ± 1.3 min, P = 0.003). No adverse events or evidence of recurrence of neuromuscular block were observed. In patients with renal failure, sugammadex (4 mg kg) effectively and safely reversed profound rocuronium induced neuromuscular block, but the recovery was slower than healthy patients. Clinicaltrials.gov identifier NCT01785758.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

PubMed

Murray, Michael J; DeBlock, Heidi; Erstad, Brian; Gray, Anthony; Jacobi, Judi; Jordan, Che; McGee, William; McManus, Claire; Meade, Maureen; Nix, Sean; Patterson, Andrew; Sands, M Karen; Pino, Richard; Tescher, Ann; Arbour, Richard; Rochwerg, Bram; Murray, Catherine Friederich; Mehta, Sangeeta

2016-11-01

To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density: A study in 417 older women.

PubMed

Belavý, Daniel L; Armbrecht, Gabriele; Blenk, Tilo; Bock, Oliver; Börst, Hendrikje; Kocakaya, Emine; Luhn, Franziska; Rantalainen, Timo; Rawer, Rainer; Tomasius, Frederike; Willnecker, Johannes; Felsenberg, Dieter

2016-02-01

We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD. Copyright © 2015 Elsevier Inc. All rights reserved.

49 CFR 1242.51 - Dismantling retired property and depreciation (accounts XX-27-39 and 62-27-00).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Dismantling retired property and depreciation (accounts XX-27-39 and 62-27-00). 1242.51 Section 1242.51 Transportation Other Regulations Relating to... (accounts XX-27-39 and 62-27-00). Separate common expenses in proportion to the separation of common repair...

49 CFR 1242.37 - Dismantling retired property and depreciation (accounts XX-26-39 and 62-26-00).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Dismantling retired property and depreciation (accounts XX-26-39 and 62-26-00). 1242.37 Section 1242.37 Transportation Other Regulations Relating to... (accounts XX-26-39 and 62-26-00). Separate common expenses in each account in proportion to the separation...

Dismantling Motivational Interviewing and Feedback for College Drinkers: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Walters, Scott T.; Vader, Amanda M.; Harris, T. Robert; Field, Craig A.; Jouriles, Ernest N.

2009-01-01

Motivational interviewing (MI) is a counseling style that has been shown to reduce heavy drinking among college students. To date, all studies of MI among college students have used a format that includes a feedback profile delivered in an MI style. This study was a dismantling trial of MI and feedback among heavy-drinking college students. After…

Heavy metal contamination of surface soil in electronic waste dismantling area: site investigation and source-apportionment analysis.

PubMed

Jinhui Li; Huabo Duan; Pixing Shi

2011-07-01

The dismantling and disposal of electronic waste (e-waste) in developing countries is causing increasing concern because of its impacts on the environment and risks to human health. Heavy-metal concentrations in the surface soils of Guiyu (Guangdong Province, China) were monitored to determine the status of heavy-metal contamination on e-waste dismantling area with a more than 20 years history. Two metalloids and nine metals were selected for investigation. This paper also attempts to compare the data among a variety of e-waste dismantling areas, after reviewing a number of heavy-metal contamination-related studies in such areas in China over the past decade. In addition, source apportionment of heavy metal in the surface soil of these areas has been analysed. Both the MSW open-burning sites probably contained invaluable e-waste and abandoned sites formerly involved in informal recycling activities are the new sources of soil-based environmental pollution in Guiyu. Although printed circuit board waste is thought to be the main source of heavy-metal emissions during e-waste processing, requirement is necessary to soundly manage the plastic separated from e-waste, which mostly contains heavy metals and other toxic substances.

Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium.

PubMed

Sloan, Paul A; Rasul, Mazhar

2002-01-01

We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.

Intrinsic and extrinsic uncoupling of oxidative phosphorylation.

PubMed

Kadenbach, Bernhard

2003-06-05

This article reviews parameters of extrinsic uncoupling of oxidative phosphorylation (OxPhos) in mitochondria, based on induction of a proton leak across the inner membrane. The effects of classical uncouplers, fatty acids, uncoupling proteins (UCP1-UCP5) and thyroid hormones on the efficiency of OxPhos are described. Furthermore, the present knowledge on intrinsic uncoupling of cytochrome c oxidase (decrease of H(+)/e(-) stoichiometry=slip) is reviewed. Among the three proton pumps of the respiratory chain of mitochondria and bacteria, only cytochrome c oxidase is known to exhibit a slip of proton pumping. Intrinsic uncoupling was shown after chemical modification, by site-directed mutagenesis of the bacterial enzyme, at high membrane potential DeltaPsi, and in a tissue-specific manner to increase thermogenesis in heart and skeletal muscle by high ATP/ADP ratios, and in non-skeletal muscle tissues by palmitate. In addition, two mechanisms of respiratory control are described. The first occurs through the membrane potential DeltaPsi and maintains high DeltaPsi values (150-200 mV). The second occurs only in mitochondria, is suggested to keep DeltaPsi at low levels (100-150 mV) through the potential dependence of the ATP synthase and the allosteric ATP inhibition of cytochrome c oxidase at high ATP/ADP ratios, and is reversibly switched on by cAMP-dependent phosphorylation. Finally, the regulation of DeltaPsi and the production of reactive oxygen species (ROS) in mitochondria at high DeltaPsi values (150-200 mV) are discussed.

Ursolic Acid-enriched herba cynomorii extract induces mitochondrial uncoupling and glutathione redox cycling through mitochondrial reactive oxygen species generation: protection against menadione cytotoxicity in h9c2 cells.

PubMed

Chen, Jihang; Wong, Hoi Shan; Ko, Kam Ming

2014-01-27

Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used 'Yang-invigorating' tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.

Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting.

PubMed

Tintignac, Lionel A; Brenner, Hans-Rudolf; Rüegg, Markus A

2015-07-01

The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia. Copyright © 2015 the American Physiological Society.

Dismantling of Radium-226 Coal Level Gauges: Encountered Problems and How to Solve

DOE Office of Scientific and Technical Information (OSTI.GOV)

Punnachaiya, M.; Nuanjan, P.; Moombansao, K.

2006-07-01

This paper describes the techniques for dismantling of disused-sealed Radium-226 (Ra-226) coal level gauges which the source specifications and documents were not available, including problems occurred during dismantling stage and the decision making in solving all those obstacles. The 2 mCi (20 pieces), 6 mCi (20 pieces) and 6.6 mCi (30 pieces) of Ra-226 hemi-spherically-shaped with lead-filled coal level gauges were used in industrial applications for electric power generation. All sources needed to be dismantled for further conditioning as requested by the International Atomic Energy Agency (IAEA). One of the 2 mCi Ra-226 source was dismantled under the supervision ofmore » IAEA expert. Before conditioning period, each of the 6 mCi and 6.6 mCi sources were dismantled and inspected. It was found that coal level gauges had two different source types: the sealed cylindrical source (diameter 2 cm x 2 cm length) locked with spring in lead housing for 2 mCi and 6.6 mCi; while the 6 mCi was an embedded capsule inside source holder stud assembly in lead-filled housing. Dismantling Ra-226 coal level gauges comprised of 6 operational steps: confirmation of the surface dose rate on each source activity, calculation of working time within the effective occupational dose limit, cutting the weld of lead container by electrical blade, confirmation of the Ra-226 embedded capsule size using radiation scanning technique and gamma radiography, automatic sawing of the source holder stud assembly, and transferring the source to store in lead safe box. The embedded length of 6 mCi Ra-226 capsule in its diameter 2 cm x 14.7 cm length stud assembly was identified, the results from scanning technique and radiographic film revealed the embedded source length of about 2 cm, therefore all the 6 mCi sources were safely cut at 3 cm using the automatic saw. Another occurring problem was one of the 6.6 mCi spring type source stuck inside its housing because the spring was deformed and there was previously a leakage on inner source housing. Thus, during manufacturing the filled-lead for shielding passed through this small hole and fixed the deformed spring together with the source. The circular surface of inner hole was measured and slowly drilled at a diameter 2.2 cm behind shielding, till the spring and the fixed lead sheet were cut, therefore the source could be finally hammered out. The surface dose rate of coal level gauges before weld cutting was 10-15 mR/hr and the highest dose rate at the position of the weld cutter was 2.5 mR/hr. The total time for each weld cutting and automatic sawing was 2-3 minutes and 1 minute, respectively. The source was individually and safely transferred to store in lead safe box using a 1-meter length tong and a light container with 1 meter length handle. The total time for Ra-226 (70 pieces) dismantling, including the encountered problems and their troubles shooting took 4 days operation in which the total dose obtained by 18 operators were ranged from 1-38 {mu}Sv. The dismantling team safely completed the activities within the effective dose limit for occupational exposure of 20 mSv/year (80 {mu}Sv/day). (authors)« less

Raised intracellular [Ca2+] abolishes excitation-contraction coupling in skeletal muscle fibres of rat and toad.

PubMed Central

Lamb, G D; Junankar, P R; Stephenson, D G

1995-01-01

1. Raising the intracellular [Ca2+] for 10 s at 23 degrees C abolished depolarization-induced force responses in mechanically skinned muscle fibres of toad and rat (half-maximal effect at 10 and 23 microM, respectively), without affecting the ability of caffeine or low [Mg2+] to open the ryanodine receptor (RyR)/Ca2+ release channels. Thus, excitation-contraction coupling was lost, even though the Ca2+ release channels were still functional. Coupling could not be restored in the duration of an experiment (up to 1 h). 2. The Ca(2+)-dependent uncoupling had a Q10 > 3.5, and was three times slower at pH 5.8 than at pH 7.1. Sr2+ caused similar uncoupling at twenty times higher concentration, but Mg2+, even at 10 mM, was ineffective. Uncoupling was not noticeably affected by removal of ATP or application of protein kinase or phosphatase inhibitors. 3. Confocal laser scanning microscopy showed that the transverse tubular system was sealed in its entirety in mechanically skinned fibres and that its integrity was maintained in uncoupled fibres. Electron microscopy revealed distorted or severed triad junctions and Z-line aberrations in uncoupled fibres. 4. Only when uncoupling was induced at a relatively slow rate (e.g. over 60 s with 2.5 microM Ca2+) could it be prevented by the protease inhibitor leupeptin (1 mM). Immunostaining of Western blots showed no evidence of proteolysis of the RyR, the alpha 1-subunit of dihydropyridine receptor (DHPR) or triadin in uncoupled fibres. 5. Fibres which, whilst intact, were stimulated repeatedly by potassium depolarization with simultaneous application of 30 mM caffeine showed reduced responsiveness after skinning to depolarization but not to caffeine. Rapid release of endogenous Ca2+, or raised [Ca2+] under conditions which minimized the loss of endogenous diffusible myoplasmic molecules from the skinned fibre, caused complete uncoupling. Taken together, these results suggest that Ca(2+)-dependent uncoupling can also occur in intact fibres. 6. This Ca(2+)-dependent loss of depolarization-induced Ca2+ release may play an important feedback role in muscle by stopping Ca2+ release in localized areas where it is excessive and may be responsible for long-lasting muscle fatigue after severe exercise, as well as contributing to muscle weakness in various dystrophies. Images Figure 1 Figure 7 Figure 9 PMID:8847631

Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction.

PubMed

Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

2015-12-01

[Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period.

Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction

PubMed Central

Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

2015-01-01

[Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period. PMID:26834316

Chooz A, First Pressurized Water Reactor to be Dismantled in France - 13445

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boucau, Joseph; Mirabella, C.; Nilsson, Lennart

2013-07-01

Nine commercial nuclear power plants have been permanently shut down in France to date, of which the Chooz A plant underwent an extensive decommissioning and dismantling program. Chooz Nuclear Power Station is located in the municipality of Chooz, Ardennes region, in the northeast part of France. Chooz B1 and B2 are 1,500 megawatt electric (MWe) pressurized water reactors (PWRs) currently in operation. Chooz A, a 305 MWe PWR implanted in two caves within a hill, began operations in 1967 and closed in 1991, and will now become the first PWR in France to be fully dismantled. EDF CIDEN (Engineering Centermore » for Dismantling and Environment) has awarded Westinghouse a contract for the dismantling of its Chooz A reactor vessel (RV). The project began in January 2010. Westinghouse is leading the project in a consortium with Nuvia France. The project scope includes overall project management, conditioning of the reactor vessel (RV) head, RV and RV internals segmentation, reactor nozzle cutting for lifting the RV out of the pit and seal it afterwards, dismantling of the RV thermal insulation, ALARA (As Low As Reasonably Achievable) forecast to ensure acceptable doses for the personnel, complementary vacuum cleaner to catch the chips during the segmentation work, needs and facilities, waste characterization and packaging, civil work modifications, licensing documentation. The RV and RV internals will be segmented based on the mechanical cutting technology that Westinghouse applied successfully for more than 13 years. The segmentation activities cover the cutting and packaging plan, tooling design and qualification, personnel training and site implementation. Since Chooz A is located inside two caves, the project will involve waste transportation from the reactor cave through long galleries to the waste buffer area. The project will end after the entire dismantling work is completed, and the waste storage is outside the caves and ready to be shipped either to the ANDRA (French National Radioactive Waste Management Agency) waste disposal facilities - (for low-level waste [LLW] and very low-level waste [VLLW], which are considered short lived) - or to the EDF Interim Storage Facility planned to be built on another site - (for low- and intermediate-level waste [LILW], which is considered long lived). The project has started with a detailed conceptual study that determines the step-by-step approach for dismantling the reactor and eventually supplying the packed containers ready for final disposal. All technical reports must be verified and approved by EDF and the French Nuclear Safety Authority before receiving the authorization to start the site work. The detailed conceptual study has been completed to date and equipment design and manufacturing is ongoing. This paper will present the conceptual design of the reactor internals segmentation and packaging process that will be implemented at Chooz A, including the planning, methodology, equipment, waste management, and packaging strategy. (authors)« less

Hydroxynonenal-stimulated activity of the uncoupling protein in Acanthamoeba castellanii mitochondria under phosphorylating conditions.

PubMed

Woyda-Ploszczyca, Andrzej; Jarmuszkiewicz, Wieslawa

2013-05-01

The influence of 4-hydroxy-2-nonenal (HNE), a lipid peroxidation end product, on the activity of the amoeba Acanthamoeba castellanii uncoupling protein (AcUCP) in isolated phosphorylating mitochondria was studied. Under phosphorylating conditions, exogenously added HNE induced GTP-sensitive AcUCP-mediated mitochondrial uncoupling. The HNE-induced proton leak decreased the yield of oxidative phosphorylation in an HNE concentration-dependent manner. The present study describes how the contributions of ATP synthase and HNE-induced AcUCP in phosphorylating respiration vary when the rate of succinate oxidation is decreased by limiting succinate uptake or inhibiting complex III activity within the range of a constant membrane potential. In phosphorylating mitochondria, at a given HNE concentration (100 μM), the efficiency of AcUCP in mitochondrial uncoupling increased as the respiratory rate decreased because the AcUCP contribution remained constant while the ATP synthase contribution decreased with the respiratory rate. HNE-induced uncoupling can be inhibited by GTP only when ubiquinone is sufficiently oxidized, indicating that in phosphorylating A. castellanii mitochondria, the sensitivity of AcUCP activity to GTP depends on the redox state of the membranous ubiquinone.

Hyperthyroidism increases the uncoupled ATPase activity and heat production by the sarcoplasmic reticulum Ca2+-ATPase.

PubMed

Arruda, Ana Paula; Da-Silva, Wagner S; Carvalho, Denise P; De Meis, Leopoldo

2003-11-01

The sarcoplasmic reticulum Ca2+-ATPase is able to modulate the distribution of energy released during ATP hydrolysis, so that a portion of energy is used for Ca2+ transport (coupled ATPase activity) and a portion is converted into heat (uncoupled ATPase activity). In this report it is shown that T4 administration to rabbits promotes an increase in the rates of both the uncoupled ATPase activity and heat production in sarcoplasmic reticulum vesicles, and that the degree of activation varies depending on the muscle type used. In white muscles hyperthyroidism promotes a 0.8-fold increase of the uncoupled ATPase activity and in red muscle a 4-fold increase. The yield of vesicles from hyperthyroid muscles is 3-4-fold larger than that obtained from normal muscles; thus the rate of heat production by the Ca2+-ATPase expressed in terms of g of muscle in hyperthyroidism is increased by a factor of 3.6 in white muscles and 12.0 in red muscles. The data presented suggest that the Ca2+-ATPase uncoupled activity may represent one of the heat sources that contributes to the enhanced thermogenesis noted in hyperthyroidism.

Fatigue in neuromuscular disorders: focus on Guillain-Barré syndrome and Pompe disease.

PubMed

de Vries, J M; Hagemans, M L C; Bussmann, J B J; van der Ploeg, A T; van Doorn, P A

2010-03-01

Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain-Barré syndrome and Pompe disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but in reaction to neuromuscular disease fatigue of central origin can be an important protective mechanism to restrict further damage. In most cases, severity of fatigue seems to be related with disease severity, possibly with the exception of fatigue occurring in a monophasic disorder like Guillain-Barré syndrome. Treatment of fatigue in neuromuscular disease starts with symptomatic treatment of the underlying disease. When symptoms of fatigue persist, non-pharmacological interventions, such as exercise and cognitive behavioral therapy, can be initiated.

A Randomized Clinical Trial to Dismantle Components of Cognitive Processing Therapy for Posttraumatic Stress Disorder in Female Victims of Interpersonal Violence

ERIC Educational Resources Information Center

Resick, Patricia A.; Galovski, Tara E.; Uhlmansiek, Mary O'Brien; Scher, Christine D.; Clum, Gretchen A.; Young-Xu, Yinong

2008-01-01

The purpose of this experiment was to conduct a dismantling study of cognitive processing therapy in which the full protocol was compared with its constituent components--cognitive therapy only (CPT-C) and written accounts (WA)--for the treatment of posttraumatic stress disorder (PTSD) and comorbid symptoms. The intent-to-treat (ITT) sample…

Steps toward dismantling poverty for working, poor women.

PubMed

Froehlich, Jeanette

2005-01-01

The majority of the world's poor people are women and many of them spend long hours doing paid and unpaid work. Pay inequities between men and women persist and income inequalities between the rich and poor are deepening. Working poor females, especially working poor mothers, struggle against considerable odds. This situation, and some steps that healthcare professionals can take toward dismantling poverty are addressed.

Associations between polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress in people living near e-waste recycling facilities in China.

PubMed

Lu, Shao-You; Li, Yan-Xi; Zhang, Jian-Qing; Zhang, Tao; Liu, Gui-Hua; Huang, Ming-Zhi; Li, Xiao; Ruan, Ju-Jun; Kannan, Kurunthachalam; Qiu, Rong-Liang

2016-09-01

Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ∑10OH-PAHs determined in e-waste recycling area (GM: 25.4μg/g Cre) were significantly higher (p<0.05) than those found in both rural (11.7μg/g Cre) and urban (10.9μg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6μg/g Cre) showed significantly higher (p<0.01) urinary Σ10OH-PAHs concentrations than non-occupationally exposed people (23.2μg/g Cre) living in the e-waste recycling site. The differences in urinary Σ10OH-PAHs levels between smokers (23.4μg/g Cre) and non-smokers (24.7μg/g Cre) were not significant (p>0.05) in e-waste dismantling sites, while these differences were significant (p<0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Σ10OH-PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1-hydroxypyrene (1-PYR) (r=0.284, p<0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Respiratory uncoupling by increased H(+) or K(+) flux is beneficial for heart mitochondrial turnover of reactive oxygen species but not for permeability transition.

PubMed

Morota, Saori; Piel, Sarah; Hansson, Magnus J

2013-09-22

Ischemic preconditioning has been proposed to involve changes in mitochondrial H(+) and K(+) fluxes, in particular through activation of uncoupling proteins and ATP-sensitive K(+) channels (MitoKATP). The objectives of the present study were to explore how increased H(+) and K(+) fluxes influence heart mitochondrial physiology with regard to production and scavenging of reactive oxygen species (ROS), volume changes and resistance to calcium-induced mitochondrial permeability transition (mPT). Isolated rat heart mitochondria were exposed to a wide concentration range of the protonophore CCCP or the potassium ionophore valinomycin to induce increased H(+) and K(+) conductance, respectively. Simultaneous monitoring of mitochondrial respiration and calcium retention capacity (CRC) demonstrated that the relative increase in respiration caused by valinomycin or CCCP correlated with a decrease in CRC, and that no level of respiratory uncoupling was associated with enhanced resistance to mPT. Mitochondria suspended in hyperosmolar buffer demonstrated a dose-dependent reduction in CRC with increasing osmolarity. However, mitochondria in hypoosmolar buffer to increase matrix volume did not display increased CRC. ROS generation was reduced by both K(+)- and H(+)-mediated respiratory uncoupling. The ability of heart mitochondria to detoxify H2O2 was substantially greater than the production rate. The H2O2 detoxification was dependent on respiratory substrates and was dramatically decreased following calcium-induced mPT, but was unaffected by uncoupling via increased K(+) and H(+) conductance. It is concluded that respiratory uncoupling is not directly beneficial to rat heart mitochondrial resistance to calcium overload irrespective of whether H(+) or K(+) conductance is increased. The negative effects of respiratory uncoupling thus probably outweigh the reduction in ROS generation and a potential positive effect by increased matrix volume, resulting in a net sensitization of heart mitochondria to mPT activation.

Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation.

PubMed

Zhang, Jun-Xia; Qu, Xin-Liang; Chu, Peng; Xie, Du-Jiang; Zhu, Lin-Lin; Chao, Yue-Lin; Li, Li; Zhang, Jun-Jie; Chen, Shao-Liang

2018-05-01

Uncoupled endothelial nitric oxide synthase (eNOS) produces O 2 - instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O 2 - production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O 2 - burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O 2 - releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Neuromuscular blockade in cardiac surgery: an update for clinicians.

PubMed

Hemmerling, Thomas M; Russo, Gianluca; Bracco, David

2008-01-01

There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary) sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

Preparing for the unexpected: special considerations and complications after sugammadex administration.

PubMed

Iwasaki, Hajime; Renew, J Ross; Kunisawa, Takayuki; Brull, Sorin J

2017-10-17

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.

[Pollution Characteristics and Ecological Risk of PBDEs in Water and Sediment from an Electronic Waste Dismantling Area in Taizhou].

PubMed

Chen, Xiang-ping; Peng, Bao-qi; Lü, Su-ping; Chen, Qiang; Zhang, Yong; Huang, Chang-jiang; Dong, Qiao-xiang

2016-05-15

An e-waste dismantling industrial park of Taizhou was selected as the sampling center, within a radius of 16 km, and a total of 30 sampling sites were designed in three circles as follows: C (3 km), S (5-10 km) and R (10-16 km). Pollution characteristics and ecological risk of polybrominated diphenyl ethers (PBDEs) in water and sediments were investigated. The concentrations of PBDEs in water ranged from 9.4 to 57.2 ng · L⁻¹, with a mean value of 25.9 ng · L⁻¹; and 3.7 to 38,775 ng · g⁻¹, with an average of 2 779 ng · g⁻¹ in sediments. BDE-209 was the predominant congener. The spatial distribution patterns of PBDE levels in water and sediment were both in the following order: C > S > R. Furthermore, the concentrations of PBDEs in sediments showed significant negative correlation against the distance from the industrial park (P < 0.01). Compared with other regions around the world, the PBDEs contamination was more serious in the area, which indicated that e-waste dismantling activity was one of the significant sources for PBDEs pollution. It was estimated that a total of 30. 7 t PBDEs (including 28. 9 t BDE- 209) was discharged into surrounding environment as a result of dismantling industrial activities in last 40 years. A preliminary ecological risk assessment for PBDEs in water and sediments was conducted by hazard quotient method. The results demonstrated that the Penta-BDEs in the center of e-waste dismantling area ( a radius of 1.5 km) was at particularly high risk level and could cause serious influence on the ecological safety and human health.

Systems and methods for dismantling a nuclear reactor

DOEpatents

Heim, Robert R; Adams, Scott Ryan; Cole, Matthew Denver; Kirby, William E; Linnebur, Paul Damon

2014-10-28

Systems and methods for dismantling a nuclear reactor are described. In one aspect the system includes a remotely controlled heavy manipulator ("manipulator") operatively coupled to a support structure, and a control station in a non-contaminated portion of a workspace. The support structure provides the manipulator with top down access into a bioshield of a nuclear reactor. At least one computing device in the control station provides remote control to perform operations including: (a) dismantling, using the manipulator, a graphite moderator, concrete walls, and a ceiling of the bioshield, the manipulator being provided with automated access to all internal portions of the bioshield; (b) loading, using the manipulator, contaminated graphite blocks from the graphite core and other components from the bioshield into one or more waste containers; and (c) dispersing, using the manipulator, dust suppression and contamination fixing spray to contaminated matter.

End-of-life vehicle recycling in China: Now and the future

NASA Astrophysics Data System (ADS)

Chen, Ming

2005-10-01

The volume of in-use vehicles in China will reach 32 million by the end of 2006 and the volume of end-of-life vehicles (ELVs) will be more than 1.5 million by the end of 2005. In 2001, China passed a law regulating the disposal and recycling of ELVs. Progress has been slow, with the rate of ELV dismantling just 10% at the beginning of 2004. However, a pilot industrial demonstration of ELV dismantling and disposal was established in Shanghai in 2005. In addition, Shanghai Volkswagen established a modern engine remanufacturing plant aiming at its after-sales market. This article reviews the ELV policy, law, and administration system in China; the ELV dismantling industry; the challenges and opportunities of ELV recycling; and the state-of-the-art of remanufacturing of ELVs in China.

[Impact of a quality assurance program on the use of neuromuscular monitoring and reversal of muscle relaxants].

PubMed

Motamed, C; Bourgain, J-L

2009-04-01

As part of a quality assurance in the anaesthesia department, this study was designed to enhance the rate of neuromuscular blockade monitoring for patients receiving muscle relaxant during anaesthesia. After approval of our local ethical committee, we assessed 200 computerized anaesthesia records in which neuromuscular relaxants were used. The following data were collected: demographic characteristics, durations of anaesthesia and surgery, use of neuromuscular monitoring, reversal agents and the quality of neuromuscular monitoring. The results were discussed with all anaesthesia providers of the department and an internal guideline was elaborated with the endpoint that all patients having muscle relaxants should have quantitative neuromuscular monitoring. Six months later, another assessment of 200 consecutive records collected the same data to check the efficiency of the elaborated guideline. The monitoring rate was of 67% at the first assessment and increased to 94% (p<0.05). The reversal rate was at 48% in the first assessment and was stable at the second assessment (50%). The rate of patients not monitored and not reversed decreased from 5 to 2% (p<0.05). This study shows that as part of a quality assurance program systematic quantitative monitoring of neuromuscular blockade can be significantly increased.

Single Fiber Electromyographic Jitter to Detect Acute Changes in Neuromuscular Function in Young and Adult Rats

EPA Science Inventory

Introduction: Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapt...

Management of Cardiac Involvement in NeuroMuscular Diseases: Review

PubMed Central

Bouhouch, Rachida; Elhouari, Tarik; Oukerraj, Latifa; Fellat, Ibtissam; Zarzur, Jamila; Bennani, Rajaa; Arharbi, Mhamed

2008-01-01

Neuromuscular Diseases are a heterogeneous molecular, clinical and prognosis group. Progress has been achieved in the understanding and classification of these diseases. Cardiac involvement in neuromuscular diseases namely conduction disorders, ventricular dilatation and dilated cardiomyopathy with its impact on prognosis, is often dissociated from the peripheral myopathy. Therefore, close surveillance is mandatory in the affected patients. In this context, preventive therapy (beta-blockers and angiotensin converting enzyme inhibitors) has been recently recommended in the most common Neuromuscular Diseases, Duchenne Muscular Dystrophy and Myotonic Dystrophy. PMID:19337361

Historical and projected carbon balance of mature black spruce ecosystems across north america: The role of carbon-nitrogen interactions

USGS Publications Warehouse

Clein, Joy S.; McGuire, A.D.; Zhang, X.; Kicklighter, D.W.; Melillo, J.M.; Wofsy, S.C.; Jarvis, P.G.; Massheder, J.M.

2002-01-01

The role of carbon (C) and nitrogen (N) interactions on sequestration of atmospheric CO2 in black spruce ecosystems across North America was evaluated with the Terrestrial Ecosystem Model (TEM) by applying parameterizations of the model in which C-N dynamics were either coupled or uncoupled. First, the performance of the parameterizations, which were developed for the dynamics of black spruce ecosystems at the Bonanza Creek Long-Term Ecological Research site in Alaska, were evaluated by simulating C dynamics at eddy correlation tower sites in the Boreal Ecosystem Atmosphere Study (BOREAS) for black spruce ecosystems in the northern study area (northern site) and the southern study area (southern site) with local climate data. We compared simulated monthly growing season (May to September) estimates of gross primary production (GPP), total ecosystem respiration (RESP), and net ecosystem production (NEP) from 1994 to 1997 to available field-based estimates at both sites. At the northern site, monthly growing season estimates of GPP and RESP for the coupled and uncoupled simulations were highly correlated with the field-based estimates (coupled: R2= 0.77, 0.88 for GPP and RESP; uncoupled: R2 = 0.67, 0.92 for GPP and RESP). Although the simulated seasonal pattern of NEP generally matched the field-based data, the correlations between field-based and simulated monthly growing season NEP were lower (R2 = 0.40, 0.00 for coupled and uncoupled simulations, respectively) in comparison to the correlations between field-based and simulated GPP and RESP. The annual NEP simulated by the coupled parameterization fell within the uncertainty of field-based estimates in two of three years. On the other hand, annual NEP simulated by the uncoupled parameterization only fell within the field-based uncertainty in one of three years. At the southern site, simulated NEP generally matched field-based NEP estimates, and the correlation between monthly growing season field-based and simulated NEP (R2 = 0.36, 0.20 for coupled and uncoupled simulations, respectively) was similar to the correlations at the northern site. To evaluate the role of N dynamics in C balance of black spruce ecosystems across North America, we simulated historical and projected C dynamics from 1900 to 2100 with a global-based climatology at 0.5?? resolution (latitude ?? longitude) with both the coupled and uncoupled parameterizations of TEM. From analyses at the northern site, several consistent patterns emerge. There was greater inter-annual variability in net primary production (NPP) simulated by the uncoupled parameterization as compared to the coupled parameterization, which led to substantial differences in inter-annual variability in NEP between the parameterizations. The divergence between NPP and heterotrophic respiration was greater in the uncoupled simulation, resulting in more C sequestration during the projected period. These responses were the result of fundamentally different responses of the coupled and uncoupled parameterizations to changes in CO2 and climate. Across North American black spruce ecosystems, the range of simulated decadal changes in C storage was substantially greater for the uncoupled parameterization than for the coupled parameterization. Analysis of the spatial variability in decadal responses of C dynamics revealed that C fluxes simulated by the coupled and uncoupled parameterizations have different sensitivities to climate and that the climate sensitivities of the fluxes change over the temporal scope of the simulations. The results of this study suggest that uncertainties can be reduced through (1) factorial studies focused on elucidating the role of C and N interactions in the response of mature black spruce ecosystems to manipulations of atmospheric CO2 and climate, (2) establishment of a network of continuous, long-term measurements of C dynamics across the range of mature black spruce ecosystems in North America, and (3) ancillary measureme

Efficacy and Cost-Effectiveness of a Minimal Intervention to Prevent Smoking Relapse: Dismantling the Effects of Amount of Content Versus Contact.

ERIC Educational Resources Information Center

Brandon, Thomas H.; Meade, Cathy D.; Herzog, Thaddeus A.; Chirikos, Thomas N.; Webb, Monica S.; Cantor, Alan B.

2004-01-01

Relapse prevention remains a major challenge to smoking cessation efforts. T. H. Brandon, B. N. Collins, L. M. Juliano, and A. B. Lazev (2000) found that a series of 8 empirically based relapse-prevention booklets mailed to ex-smokers over 1 year significantly reduced relapse. This study dismantled 2 components of that intervention: the amount of…

Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency.

PubMed

Thomsen, J L; Nielsen, C V; Palmqvist, D F; Gätke, M R

2015-07-01

Patients with butyrylcholinesterase (BChE) deficiency can experience prolonged paralysis after receiving suxamethonium or mivacurium. We hypothesized that patients suspected of BChE deficiency had a higher risk of being awakened while paralysed and having respiratory complications if neuromuscular monitoring was not applied before awakening. We retrospectively included patients referred to the Danish Cholinesterase Research Unit between 2004 and 2012 on suspicion of BChE deficiency. We collected data on genotype, BChE activity, neuromuscular blocking agents administered, neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation <90%, assisted ventilation, reintubation of the trachea, and pulmonary aspiration. Patients were classified as prematurely awakened if anaesthesia had been terminated while the patient was still paralysed. We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored and monitored patients, respectively (P<0.001, Fisher's exact test). In 11 of the monitored patients, the results of neuromuscular monitoring were interpreted as equipment failure or were disregarded. Respiratory complications occurred in 19 (25%) and five (10%) of the unmonitored and monitored patients, respectively (P=0.06). Patients with BChE deficiency are at higher risk of being awakened while paralysed if neuromuscular monitoring is not applied or used; neuromuscular monitoring is recommended whenever a neuromuscular blocking agent is administered. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Recommendations on the use of deep neuromuscular blockade by anaesthesiologists and surgeons. AQUILES (Anestesia QUIrúrgica para Lograr Eficiencia y Seguridad) Consensus.

PubMed

Errando-Oyonarte, C L; Moreno-Sanz, C; Vila-Caral, P; Ruiz de Adana-Belbel, J C; Vázquez-Alonso, E; Ramírez-Rodríguez, J M; Veiga-Ruiz, G; Guasch-Arévalo, E; Lora-Tamayo D'Ocón, J I

2017-02-01

Neuromuscular blockade enables airway management, ventilation and surgical procedures. However there is no national consensus on its routine clinical use. The objective was to establish the degree of agreement among anaesthesiologists and general surgeons on the clinical use of neuromuscular blockade in order to make recommendations to improve its use during surgical procedures. Multidisciplinary consensus study in Spain. Anaesthesiologists experts in neuromuscular blockade management (n=65) and general surgeons (n=36) were included. Delphi methodology was selected. A survey with 17 final questions developed by a dedicated scientific committee was designed. The experts answered the successive questions in two waves. The survey included questions on: type of surgery, type of patient, benefits/harm during and after surgery, impact of objective neuromuscular monitoring and use of reversal drugs, viability of a multidisciplinary and efficient approach to the whole surgical procedure, focussing on the level of neuromuscular blockade. Five recommendations were agreed: 1) deep neuromuscular blockade is very appropriate for abdominal surgery (degree of agreement 94.1%), 2) and in obese patients (76.2%); 3) deep neuromuscular blockade maintenance until end of surgery might be beneficial in terms of clinical aspects, such as as immobility or better surgical access (86.1 to 72.3%); 4) quantitative monitoring and reversal drugs availability is recommended (89.1%); finally 5) anaesthesiologists/surgeons joint protocols are recommended. Collaboration among anaesthesiologists and surgeons has enabled some general recommendations to be established on deep neuromuscular blockade use during abdominal surgery. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Neuromuscular complications of thyrotoxicosis.

PubMed

Kung, Annie W C

2007-11-01

Thyroid hormones exert multiple effects on the neuromuscular system and the brain, with the most important being their role in stimulating the development and differentiation of the neuromuscular system and brain in foetal and neonatal life. In the presence of hyperthyroidism, muscular and neurological symptoms may be the presenting clinical features of the disease. The frequency and severity of neuromuscular complications vary considerably and are probably related to the degree of hyperthyroidism, although in some patients the neuromuscular dysfunction is caused by associated disorders rather than by hyperthyroidism per se. This update focuses on the most common neurological and muscular disorders that occur in patients with thyrotoxicosis. It is beyond the scope of this paper to discuss thyroid eye disease and cardiac complications, in themselves separate complications of specific myocytes.

Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

PubMed Central

Berghella, Libera; Ferraro, Elisabetta

2012-01-01

Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

Use of Single Fiber Electromyographic Jitter to Detect Acute Changes in Neuromuscular Function in Young and Adult Rats

EPA Science Inventory

INTRODUCTION: Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapt...

The immediate effect of neuromuscular joint facilitation on the rotation of the tibia during walking.

PubMed

Li, Desheng; Huang, Qiuchen; Huo, Ming; Hiiragi, Yukinobu; Maruyama, Hitoshi

2017-01-01

[Purpose] The aim of this study was to investigate the change in tibial rotation during walking among young adults after neuromuscular joint facilitation therapy. [Subjects and Methods] The subjects were twelve healthy young people (6 males, 6 females). A neuromuscular joint facilitation intervention and nonintervention were performed. The interventions were performed one after the other, separated by a 1-week interval. The order of the interventions was completely randomized. The rotation of the tibia during walking was evaluated before and after treatment. [Results] The neuromuscular joint facilitation group demonstrated increased lateral rotation of the tibia in the overall gait cycle and stance phase, and decreased medial rotation of the tibia in the overall gait cycle, stance phase, and swing phase after the neuromuscular joint facilitation intervention. In the control group, there were no significant differences. [Conclusion] These results suggest neuromuscular joint facilitation intervention has an immediate effect on the rotational function of the knee.

Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent

PubMed Central

Welliver, Mark; McDonough, John; Kalynych, Nicholas; Redfern, Robert

2008-01-01

Neuromuscular blockade, induced by neuromuscular blocking agents, has allowed prescribed immobility, improved surgical exposure, optimal airway management conditions, and facilitated mechanical ventilation. However, termination of the effects of neuromuscular blocking agents has, until now, remained limited. A novel cyclodextrin encapsulation process offers improved termination of the paralytic effects of aminosteroidal non-depolarizing neuromuscular blocking agents. Sugammadex sodium is the first in a new class of drug called selective relaxant binding agents. Currently, in clinical trials, sugammadex, a modified gamma cyclodextrin, has shown consistent and rapid termination of neuromuscular blockade with few side effects. The pharmacology of cyclodextrins in general and sugammadex in particular, together with the results of current clinical research are reviewed. The ability of sugammadex to terminate the action of neuromuscular blocking agents by direct encapsulation is compared to the indirect competitive antagonism of their effects by cholinesterase inhibitors. Also discussed are the clinical implications that extend beyond fast, effective reversal, including numerous potential perioperative benefits. PMID:19920893

An exploratory study of physical activity and perceived barriers to exercise in ambulant people with neuromuscular disease compared with unaffected controls.

PubMed

Phillips, Margaret; Flemming, Nicola; Tsintzas, Kostas

2009-08-01

To determine activity patterns and perceived barriers to exercise in ambulant people with neuromuscular disease compared with ambulatory controls. Prospective controlled parallel group design. Outpatient clinic and community. Thirteen ambulatory people with neuromuscular disease and 18 ambulatory controls. Heart rates were recorded during sedentary activity and treadmill walking at various speeds to indicate activity threshold (flex heart rate), followed by ambulatory heart rate monitoring over two weekdays and one weekend day. The EPIC-Norfolk Physical Activity Questionnaire-2 and Barriers to Physical Activity and Disability Survey were completed. Participants with neuromuscular disease were less active than controls as estimated by both the EPIC-Norfolk Physical Activity Questionnaire-2, P<0.004, and the flex heart rate method, P<0.05. The number of perceived barriers was greater in the neuromuscular group, a mean of 7 (SD 4.2) barriers, compared with mean 3 (SD 2.1) barriers for controls, P<0.05. Specific barriers differed, with the barriers of 'pain', 'lack of energy' and 'exercise is too difficult' showing the greatest discrepancy and being higher in the neuromuscular disease group. Physical activity, as determined by two different methods, was less and barriers to exercise greater in people with neuromuscular disease compared with healthy controls. Specific barriers were different in the two groups. This information could assist in the design of achievable and effective exercise programmes for people with neuromuscular disease.

Neuromuscular Blockade and Reversal Agents: A Primer for Postanesthesia Nurses.

ERIC Educational Resources Information Center

Pesci, Barbara R.

1986-01-01

Presents a comprehensive review of neuromuscular blocking agents, reversal agents used in anesthesia, and factors affecting reversal. It is aimed at nurses who provide care to patients recovering from anesthesia. It discusses the neuromuscular transmission system, depolarizing muscle relaxants, nondepolarizing blocking agents, and criteria for…

Calorie restriction in mice overexpressing UCP3: evidence that prior mitochondrial uncoupling alters response.

PubMed

Estey, Carmen; Seifert, Erin L; Aguer, Céline; Moffat, Cynthia; Harper, Mary-Ellen

2012-05-01

Calorie restriction (CR) without malnutrition is the only intervention to consistently increase lifespan in all species tested, and lower age-related pathologies in mammals including humans. It has been suggested that uncoupling of mitochondrial oxidative phosphorylation, using chemical uncouplers, mimics CR, and that overlapping mechanisms underlie the phenotypic changes induced by uncoupling and CR. We aimed to critically assess this using a unique mouse model of skeletal muscle-targeted UCP3-induced uncoupling (UCP3Tg), and focused our studies mainly on skeletal muscle mitochondria. Compared to ad libitum fed Wt mice, skeletal muscle mitochondria from ad libitum fed UCP3Tg mice showed higher basal uncoupling and lower H(2)O(2) emission, with unchanged maximal oxidative phosphorylation, and mitochondrial content. UCP3Tg CR mice showed some tendency for differential adaptation to CR, with lowered H(+) leak conductance and evidence for higher H(2)O(2) emission from skeletal muscle mitochondria following 2 weeks CR, and failure to lower H(2)O(2) emission after 1 month CR. Differential adaptation was also apparent at the whole body level: while UCP3Tg CR mice lost as much weight as Wt CR mice, the proportion of muscle lost was higher in UCP3Tg mice. However, a striking outcome of our studies was the absence of change with CR in many of the parameters of mitochondrial function and content that we measured in mice of either genotype. Overall, our study raises the question of whether CR can consistently modify skeletal muscle mitochondria; alterations with CR may only be apparent under certain conditions such as during the 2 wk CR intervention in the UCP3Tg mice. Copyright © 2012 Elsevier Inc. All rights reserved.

SR4 Uncouples Mitochondrial Oxidative Phosphorylation, Modulates AMP-dependent Kinase (AMPK)-Mammalian Target of Rapamycin (mTOR) Signaling, and Inhibits Proliferation of HepG2 Hepatocarcinoma Cells*

PubMed Central

Figarola, James L.; Singhal, Jyotsana; Tompkins, Joshua D.; Rogers, George W.; Warden, Charles; Horne, David; Riggs, Arthur D.; Awasthi, Sanjay; Singhal, Sharad S.

2015-01-01

Mitochondrial oxidative phosphorylation produces most of the energy in aerobic cells by coupling respiration to the production of ATP. Mitochondrial uncouplers, which reduce the proton gradient across the mitochondrial inner membrane, create a futile cycle of nutrient oxidation without generating ATP. Regulation of mitochondrial dysfunction and associated cellular bioenergetics has been recently identified as a promising target for anticancer therapy. Here, we show that SR4 is a novel mitochondrial uncoupler that causes dose-dependent increase in mitochondrial respiration and dissipation of mitochondrial membrane potential in HepG2 hepatocarcinoma cells. These effects were reversed by the recoupling agent 6-ketocholestanol but not cyclosporin A and were nonexistent in mitochondrial DNA-depleted HepG2 cells. In isolated mouse liver mitochondria, SR4 similarly increased oxygen consumption independent of adenine nucleotide translocase and uncoupling proteins, decreased mitochondrial membrane potential, and promoted swelling of valinomycin-treated mitochondria in potassium acetate medium. Mitochondrial uncoupling in HepG2 cells by SR4 results in the reduction of cellular ATP production, increased ROS production, activation of the energy-sensing enzyme AMPK, and inhibition of acetyl-CoA carboxylase and mammalian target of rapamycin signaling pathways, leading to cell cycle arrest and apoptosis. Global analysis of SR4-associated differential gene expression confirms these observations, including significant induction of apoptotic genes and down-regulation of cell cycle, mitochondrial, and oxidative phosphorylation pathway transcripts at 24 h post-treatment. Collectively, our studies demonstrate that the previously reported indirect activation of AMPK and in vitro anticancer properties of SR4 as well as its beneficial effects in both animal xenograft and obese mice models could be a direct consequence of its mitochondrial uncoupling activity. PMID:26534958

Calorie restriction in mice overexpressing UCP3: evidence that prior mitochondrial uncoupling alters response

PubMed Central

Estey, Carmen; Seifert, Erin L.; Aguer, Céline; Moffat, Cynthia; Harper, Mary-Ellen

2012-01-01

SUMMARY Calorie restriction (CR) without malnutrition is the only intervention to consistently increase lifespan in all species tested, and lower age-related pathologies in mammals including humans. It has been suggested that uncoupling of mitochondrial oxidative phosphorylation, using chemical uncouplers, mimics CR, and that overlapping mechanisms underlie the phenotypic changes induced by uncoupling and CR. We aimed to critically assess this using a unique mouse model of skeletal muscle-targeted UCP3-induced uncoupling (UCP3Tg), and focused our studies mainly on skeletal muscle mitochondria. Compared to ad libitum fed Wt mice, skeletal muscle mitochondria from ad libitum fed UCP3Tg mice showed higher basal uncoupling and lower H2O2 emission, with unchanged maximal oxidative phosphorylation, and mitochondrial content. UCP3Tg CR mice showed some tendency for differential adaptation to CR, with lowered H+ leak conductance and evidence for higher H2O2 emission from skeletal muscle mitochondria following 2 weeks CR, and failure to lower H2O2 emission after 1 month CR. Differential adaptation was also apparent at the whole body level: while UCP3Tg CR mice lost as much weight as Wt CR mice, the proportion of muscle lost was higher in UCP3Tg mice. However, a striking outcome of our studies was the absence of change with CR in many of the parameters of mitochondrial function and content that we measured in mice of either genotype. Overall, our study raises the question of whether CR can consistently modify skeletal muscle mitochondria; alterations with CR may only be apparent under certain conditions such as during the 2 wk CR intervention in the UCP3Tg mice. PMID:22406134

Exact Solutions of Coupled Multispecies Linear Reaction–Diffusion Equations on a Uniformly Growing Domain

PubMed Central

Simpson, Matthew J.; Sharp, Jesse A.; Morrow, Liam C.; Baker, Ruth E.

2015-01-01

Embryonic development involves diffusion and proliferation of cells, as well as diffusion and reaction of molecules, within growing tissues. Mathematical models of these processes often involve reaction–diffusion equations on growing domains that have been primarily studied using approximate numerical solutions. Recently, we have shown how to obtain an exact solution to a single, uncoupled, linear reaction–diffusion equation on a growing domain, 0 < x < L(t), where L(t) is the domain length. The present work is an extension of our previous study, and we illustrate how to solve a system of coupled reaction–diffusion equations on a growing domain. This system of equations can be used to study the spatial and temporal distributions of different generations of cells within a population that diffuses and proliferates within a growing tissue. The exact solution is obtained by applying an uncoupling transformation, and the uncoupled equations are solved separately before applying the inverse uncoupling transformation to give the coupled solution. We present several example calculations to illustrate different types of behaviour. The first example calculation corresponds to a situation where the initially–confined population diffuses sufficiently slowly that it is unable to reach the moving boundary at x = L(t). In contrast, the second example calculation corresponds to a situation where the initially–confined population is able to overcome the domain growth and reach the moving boundary at x = L(t). In its basic format, the uncoupling transformation at first appears to be restricted to deal only with the case where each generation of cells has a distinct proliferation rate. However, we also demonstrate how the uncoupling transformation can be used when each generation has the same proliferation rate by evaluating the exact solutions as an appropriate limit. PMID:26407013

Exact Solutions of Coupled Multispecies Linear Reaction-Diffusion Equations on a Uniformly Growing Domain.

PubMed

Simpson, Matthew J; Sharp, Jesse A; Morrow, Liam C; Baker, Ruth E

2015-01-01

Embryonic development involves diffusion and proliferation of cells, as well as diffusion and reaction of molecules, within growing tissues. Mathematical models of these processes often involve reaction-diffusion equations on growing domains that have been primarily studied using approximate numerical solutions. Recently, we have shown how to obtain an exact solution to a single, uncoupled, linear reaction-diffusion equation on a growing domain, 0 < x < L(t), where L(t) is the domain length. The present work is an extension of our previous study, and we illustrate how to solve a system of coupled reaction-diffusion equations on a growing domain. This system of equations can be used to study the spatial and temporal distributions of different generations of cells within a population that diffuses and proliferates within a growing tissue. The exact solution is obtained by applying an uncoupling transformation, and the uncoupled equations are solved separately before applying the inverse uncoupling transformation to give the coupled solution. We present several example calculations to illustrate different types of behaviour. The first example calculation corresponds to a situation where the initially-confined population diffuses sufficiently slowly that it is unable to reach the moving boundary at x = L(t). In contrast, the second example calculation corresponds to a situation where the initially-confined population is able to overcome the domain growth and reach the moving boundary at x = L(t). In its basic format, the uncoupling transformation at first appears to be restricted to deal only with the case where each generation of cells has a distinct proliferation rate. However, we also demonstrate how the uncoupling transformation can be used when each generation has the same proliferation rate by evaluating the exact solutions as an appropriate limit.

TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin.

PubMed

Goralczyk, Anna; van Vijven, Marc; Koch, Mathilde; Badowski, Cedric; Yassin, M Shabeer; Toh, Sue-Anne; Shabbir, Asim; Franco-Obregón, Alfredo; Raghunath, Michael

2017-08-01

Transient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific. Knockdown of TRPP3 repressed the expression of the brown fat signature genes uncoupling protein (UCP)-1 and peroxisome proliferator-activated receptor γ coactivator (PGC)-1α as well as attenuated forskolin-stimulated uncoupled respiration. However, indices of generalized adipogenesis, such as lipid droplet morphology and fatty acid binding protein (FAPB)-4 expression, were not affected, indicating a principal mitochondrial role of TRPP3. Conversely, activating TRPM8 with menthol up-regulated UCP-1 expression and augmented uncoupled respiration predominantly in white adipocytes (browning), whereas streptomycin antagonized TRPM8-mediated calcium entry, downregulated UCP-1 expression, and mitigated uncoupled respiration; menthol was less capable of augmenting uncoupled respiration (thermogenesis) in brown adipocytes. TRPP3 and TRPM8 hence appear to be involved in the priming of mitochondria to perform uncoupled respiration downstream of adenylate cyclase. Our results also underscore the developmental caveats of using antibiotics in adipogenic studies.-Goralczyk, A., van Vijven, M., Koch, M., Badowski, C., Yassin, M. S., Toh, S.-A., Shabbir, A., Franco-Obregón, A., Raghunath, M. TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin. © FASEB.

Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

PubMed

Stier, Antoine; Massemin, Sylvie; Criscuolo, François

2014-12-01

Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

Stockpile Dismantlement Database Training Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-11-01

This document, the Stockpile Dismantlement Database (SDDB) training materials is designed to familiarize the user with the SDDB windowing system and the data entry steps for Component Characterization for Disposition. The foundation of information required for every part is depicted by using numbered graphic and text steps. The individual entering data is lead step by step through generic and specific examples. These training materials are intended to be supplements to individual on-the-job training.

Aspects of operational radiation protection during dismantling of nuclear facilities relevant for the estimation of internal doses.

PubMed

Labarta, T

2007-01-01

Operational radiation protection of workers during the dismantling of nuclear facilities is based on the same radiation protection principles as that applied in its exploitation period with the objective of ensuring proper implementation of the as-low-as-reasonably-achievable (ALARA) principle. These principles are: prior determination of the nature and magnitude of radiological risk; classification of workplaces and workers depending on the risks; implementation of control measures; monitoring of zones and working conditions, including, if necessary, individual monitoring. From the experiences and the lessons learned during the dismantling processes carried out in Spain, several important aspects in the practical implementation of these principles that directly influence and ensure an adequate prevention of exposures and the estimation of internal doses are pointed out, with special emphasis on the estimation of internal doses due to transuranic intakes.

Hand dismantling and shredding of Japanese automobiles to determine material contents and metal recoveries. Report of investigations/1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sterner, J.W.; Steele, D.K.; Shirts, M.B.

The Bureau of Mines conducted studies on four makes of Japanese automobiles, three 1981 and one 1982 model years, received from three manufacturers to determine if their materials composition would present problems to the current technology used to process junk automobiles for metal recovery. One of each make of automobile was hand-dismantled to determine the materials composition. In addition, two nearly identical automobiles of each make were shredded at a commercial operation where all metal products and rejects were collected for analysis to determine metal and nonmetal distribution. The average weight of the four automobiles to be dismantled, less batteries,more » tools, and fluids, was 1,938.3 lb. There were no materials used in the manufacture of the late model Japanese automobiles that should present handling or processing problems to the steelmaking or secondary metal recyclers.« less

TEACHING NEUROMUSCULAR RELAXATION.

ERIC Educational Resources Information Center

NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

Neuromuscular Control and Coordination during Cycling

ERIC Educational Resources Information Center

Li, Li

2004-01-01

The neuromuscular control aspect of cycling has been investigated through the effects of modifying posture and cadence. These studies show that changing posture has a more profound influence on neuromuscular coordination than does changing slope. Most of the changes with standing posture occur late in the downstroke: increased ankle and knee joint…

Motoneuron and sensory neuron plasticity to varying neuromuscular activity levels

NASA Technical Reports Server (NTRS)

Ishihara, Akihiko; Roy, Roland R.; Ohira, Yoshinobu; Edgerton, V. Reggie

2002-01-01

The size and phenotypic properties of the neural and muscular elements of the neuromuscular unit are matched under normal conditions. When subjected to chronic decreases or increases in neuromuscular activity, however, the adaptations in these properties are much more limited in the neural compared with the muscular elements.

Effects of napping on neuromuscular fatigue in myasthenia gravis.

PubMed

Kassardjian, Charles D; Murray, Brian J; Kokokyi, Seint; Jewell, Dana; Barnett, Carolina; Bril, Vera; Katzberg, Hans D

2013-11-01

The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Copyright © 2013 Wiley Periodicals, Inc.

Effects of pivoting neuromuscular training on pivoting control and proprioception.

PubMed

Lee, Song Joo; Ren, Yupeng; Chang, Alison H; Geiger, François; Zhang, Li-Qun

2014-07-01

Pivoting neuromuscular control and proprioceptive acuity may play an important role in anterior cruciate ligament injuries. The goal of this study was to investigate whether pivoting off-axis intensity adjustable neuromuscular control training (POINT) could improve pivoting neuromuscular control, proprioceptive acuity, and functional performance. Among 41 subjects, 21 subjects participated in 18 sessions of POINT (three sessions per week for 6 wk), and 20 subjects served as controls who did their regular workout. Both groups received pre-, mid-, and postintervention evaluations. Propensity score analysis with multivariable regression adjustment was used to investigate the effect of training on pivoting neuromuscular control (pivoting instability, leg pivoting stiffness, maximum internal, and external pivoting angles), proprioceptive acuity, and functional performance in both groups. Compared with the control group, the training group significantly improved pivoting neuromuscular control as reduced pivoting instability, reduced maximum internal and external pivoting angles, increased leg pivoting stiffness, and decreased entropy of time to peak EMG in the gluteus maximus and lateral gastrocnemius under pivoting perturbations. Furthermore, the training group enhanced weight-bearing proprioceptive acuity and improved the single leg hop distance. Improvement of pivoting neuromuscular control in functional weight-bearing activities and task performances after POINT may help develop lower limb injury prevention and rehabilitation methods to reduce anterior cruciate ligament and other musculoskeletal injuries associated with pivoting sports.

Neuromuscular prehabilitation to prevent osteoarthritis after a traumatic joint injury.

PubMed

Tenforde, Adam S; Shull, Pete B; Fredericson, Michael

2012-05-01

Post-traumatic osteoarthritis (PTOA) is a process resulting from direct forces applied to a joint that cause injury and degenerative changes. An estimated 12% of all symptomatic osteoarthritis (OA) of the hip, knee, and ankle can be attributed to a post-traumatic cause. Neuromuscular prehabilitation is the process of improving neuromuscular function to prevent development of PTOA after an initial traumatic joint injury. Prehabilitation strategies include restoration of normative movement patterns that have been altered as the result of traumatic injury, along with neuromuscular exercises and gait retraining to prevent the development of OA after an injury occurs. A review of the current literature shows that no studies have been performed to evaluate methods of neuromuscular prehabilitation to prevent PTOA after a joint injury. Instead, current research has focused on management strategies after knee injuries, the value of exercise in the management of OA, and neuromuscular exercises after total knee arthroplasty. Recent work in gait retraining that alters knee joint loading holds promise for preventing the development of PTOA after joint trauma. Future research should evaluate methods of neuromuscular prehabilitation strategies in relationship to the outcome of PTOA after joint injury. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Neuromuscular response amplitude to mechanical stimulation using large-array surface electromyography in participants with and without chronic low back pain.

PubMed

Pagé, Isabelle; Nougarou, François; Descarreaux, Martin

2016-04-01

The present study aimed to compare the neuromuscular response under various mechanical stimulations of the lumbar spine in participants with and without chronic low back pain (cLBP). Four mechanical stimulations, characterized by forces ranging from 75 to 225N, were delivered using a servo-controlled linear actuator motor to the L3 spinous process of 25 healthy participants and 26 participants with cLBP. Lumbar neuromuscular responses were recorded using 64-electrodes large surface electromyography arrays. Between-group differences in the dose-response relationship (neuromuscular response amplitude according to each force level) were assessed using mixed model ANOVAs. No differences between groups were shown (all p values>.05). A significant linear relationship was observed between forces and neuromuscular response amplitudes (p<.001) indicating an increase in response amplitudes with increasing stimulation force. Responses were observed throughout the lumbar region with highest response amplitudes in the vicinity of the contacted vertebra. The neuromuscular response amplitude triggered by localized lumbar mechanical stimulations does not differ between participants with and without cLBP. Moreover, even though stimulations were delivered at specific spinal segment, a neuromuscular response, although rapidly decreasing, was observed in areas distant from the contact site. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Pivoting Neuromuscular Training on Pivoting Control and Proprioception

PubMed Central

Lee, Song Joo; Ren, Yupeng; Chang, Alison H.; Geiger, François; Zhang, Li-Qun

2014-01-01

Purpose Pivoting neuromuscular control and proprioceptive acuity may play an important role in ACL injuries. The goal of this study was to investigate whether pivoting neuromuscular training on an offaxis elliptical trainer (POINT) could improve pivoting neuromuscular control, proprioceptive acuity, and functional performance. Methods Among 41 subjects, 21 subjects participated in 18 sessions of POINT (3 sessions/week for 6 weeks), and 20 subjects served as controls who did their regular workout. Both groups received pre-, mid-, and post-intervention evaluations. Propensity score analysis with multivariable regression adjustment was used to investigate the effect of training on pivoting neuromuscular control (pivoting instability, leg pivoting stiffness, maximum internal and external pivoting angles), proprioceptive acuity, and functional performance in both groups. Results Compared to the control group, the training group significantly improved pivoting neuromuscular control as reduced pivoting instability, reduced maximum internal and external pivoting angles, increased leg pivoting stiffness, and decreased entropy of time to peak EMG in the gluteus maximus and lateral gastrocnemius under pivoting perturbations. Furthermore, the training group enhanced weight-bearing proprioceptive acuity and improved the single leg hop distance. Conclusion Improvement of pivoting neuromuscular control in functional weight-bearing activities and task performances following POINT may help develop lower limb injury prevention and rehabilitation methods to reduce ACL and other musculoskeletal injuries associated with pivoting sports. PMID:24389517

Snf1-related kinase improves cardiac mitochondrial efficiency and decreases mitochondrial uncoupling

PubMed Central

Rines, Amy K.; Chang, Hsiang-Chun; Wu, Rongxue; Sato, Tatsuya; Khechaduri, Arineh; Kouzu, Hidemichi; Shapiro, Jason; Shang, Meng; Burke, Michael A.; Abdelwahid, Eltyeb; Jiang, Xinghang; Chen, Chunlei; Rawlings, Tenley A.; Lopaschuk, Gary D.; Schumacker, Paul T.; Abel, E. Dale; Ardehali, Hossein

2017-01-01

Ischaemic heart disease limits oxygen and metabolic substrate availability to the heart, resulting in tissue death. Here, we demonstrate that the AMP-activated protein kinase (AMPK)-related protein Snf1-related kinase (SNRK) decreases cardiac metabolic substrate usage and mitochondrial uncoupling, and protects against ischaemia/reperfusion. Hearts from transgenic mice overexpressing SNRK have decreased glucose and palmitate metabolism and oxygen consumption, but maintained power and function. They also exhibit decreased uncoupling protein 3 (UCP3) and mitochondrial uncoupling. Conversely, Snrk knockout mouse hearts have increased glucose and palmitate oxidation and UCP3. SNRK knockdown in cardiac cells decreases mitochondrial efficiency, which is abolished with UCP3 knockdown. We show that Tribbles homologue 3 (Trib3) binds to SNRK, and downregulates UCP3 through PPARα. Finally, SNRK is increased in cardiomyopathy patients, and SNRK reduces infarct size after ischaemia/reperfusion. SNRK also decreases cardiac cell death in a UCP3-dependent manner. Our results suggest that SNRK improves cardiac mitochondrial efficiency and ischaemic protection. PMID:28117339

Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review.

PubMed

Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N

2016-11-01

Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing-meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies.

Genome Editing of Monogenic Neuromuscular Diseases

PubMed Central

Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N.

2017-01-01

IMPORTANCE Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. OBJECTIVES To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. EVIDENCE REVIEW PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, andmyotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9–mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. FINDINGS Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing–meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. CONCLUSIONS AND RELEVANCE Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies. PMID:27668807

Compliance With Neuromuscular Training and Anterior Cruciate Ligament Injury Risk Reduction in Female Athletes: A Meta-Analysis

PubMed Central

Sugimoto, Dai; Myer, Gregory D.; Bush, Heather M.; Klugman, Maddie F.; McKeon, Jennifer M. Medina; Hewett, Timothy E.

2012-01-01

Context No consensus exists about the influence of compliance with neuromuscular training programs on reduction of the risk of anterior cruciate ligament (ACL) injury. Objective To systematically review and synthesize the published literature to determine if compliance with neuromuscular training is associated with reduced incidence of ACL injury in young female athletes. Data Sources We searched PubMed, SPORTDiscus, CINAHL, and MEDLINE for articles published from 1995 to 2010 using the key words anterior cruciate ligament prevention, ACL prevention, knee prevention, prospective knee prevention, neuromuscular training, and neuromuscular intervention. Study Selection Criteria for inclusion required that (1) the number of ACL injuries was reported, (2) a neuromuscular training program was used, (3) females were included as participants, (4) the study design was prospective and controlled, and (5) compliance data for the neuromuscular training program were provided. Data Extraction Extracted data included the number of ACL injuries, total number of participants per group, observation time period, number of participants who completed each session, number of sessions completed by an entire team, and number of total sessions. Attendance was calculated as the number of participants who completed each session converted into a percentage of the total number of participants. Intervention completion was calculated as the number of sessions completed by an entire team converted into a percentage of the total number of training sessions. These data were used to calculate an overall rate of compliance. Data Synthesis Six of 205 identified studies were included. Incidence rates of ACL injury were lower in studies with high rates of compliance with neuromuscular training than in studies with low compliance rates (incidence rate ratio = 0.27 [95% confidence interval = 0.07, 0.80]). Tertile analysis indicated rates of ACL injury incidence were lower in studies with high compliance rates than in studies with moderate and low compliance rates (incidence rate ratio = 0.18 [95% confidence interval = 0.02, 0.77]). Conclusions A potential inverse dose-response relationship exists between compliance with neuromuscular training and incidence of ACL injury. Attending and completing recommended neuromuscular sessions appears to be an important factor for preventing ACL injuries. PMID:23182020

Factors that affect the onset of action of non-depolarizing neuromuscular blocking agents

PubMed Central

Kim, Yong Byum; Sung, Tae-Yun

2017-01-01

Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractility, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics such as onset time and duration of neuromuscular blockade should be considered along with factors that affect the effects of the NMBDs. In this review, we discuss the factors that affect the onset time of NMBDs. PMID:29046769

The on/off switches of the mitochondrial uncoupling proteins

PubMed Central

Azzu, Vian; Brand, Martin D.

2013-01-01

Mitochondrial uncoupling proteins disengage substrate oxidation from ADP phosphorylation by dissipating the proton electrochemical gradient that is required for ATP synthesis. In doing this, the archetypal uncoupling protein, UCP1, mediates adaptive thermogenesis. By contrast, its paralogues UCP2 and UCP3 are not thought to mediate whole body thermogenesis in mammals. Instead, they have been implicated in a variety of physiological and pathological processes, including protection from oxidative stress, negative regulation of glucose sensing systems and the adaptation of fatty acid oxidation capacity to starving. Although much work has been devoted to how these proteins are activated, little is known of the mechanisms that reverse this activation. PMID:20006514

Anticipatory Postural Activity During Long-Duration Space Flight

NASA Technical Reports Server (NTRS)

Layne, C. S.; Mulavara, A. P.; McDonald, P. V.; Pruett, C. J.; Koslovskaya, B.; Bloomberg, J. J.

1999-01-01

Somatosensory input has been used to modify motor output in many contexts. During space flight, the use of the lower limb musculature is much less than during activities in 1g. Consequently the neuromuscular activity of the legs is also reduced during space flight. This decrease in muscle activity contributes to muscle atrophy. Furthermore, adaptations to weightlessness contribute to posture and locomotion problems upon the return to Earth. Providing techniques to counter the negative effects of weightlessness on the neuromuscular system is an important goal, particularly during a long-duration mission. Previous work by our group has shown that lower limb neuromuscular activation that normally precedes arm movements in 1g is absent or greatly reduced during similar movements made while freefloating. However, preliminary evidence indicates that applying pressure to the feet results in enhanced neuromuscular activation during rapid arm movements performed while freefloating. This finding suggests that sensory input can be used to "drive" the motor system to increase neuromuscular functioning throughout a mission. The purpose of this investigation was to quantify the increase in neuromuscular activation resulting from the application of pressure to the feet.

Novel browning agents, mechanisms and therapeutic potentials of brown adipose tissue

USDA-ARS?s Scientific Manuscript database

Non-shivering thermogenesis is the process of biological heat production in mammals and is primarily mediated by brown adipose tissue (BAT). Through ubiquitous expression of uncoupling protein 1 (Ucp1) on the mitochondrial inner membrane, BAT displays uncoupling of fuel combustion and ATP production...

Neuromuscular complications of immune checkpoint inhibitor therapy.

PubMed

Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

2018-01-17

Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

Salvianolic acid A inhibits calpain activation and eNOS uncoupling during focal cerebral ischemia in mice.

PubMed

Mahmood, Qaisar; Wang, Guang-Fa; Wu, Gang; Wang, Huan; Zhou, Chang-Xin; Yang, Hong-Yu; Liu, Zhi-Rong; Han, Feng; Zhao, Kui

2017-02-15

Salvianolic acid A (SAA) is obtained from Chinese herb Salviae Miltiorrhizae Bunge (Labiatae), has been reported to have the protective effects against cardiovascular and neurovascular diseases. The aim of present study was to investigate the relationship between the effectiveness of SAA against neurovascular injury and its effects on calpain activation and endothelial nitric oxide synthase (eNOS) uncoupling. SAA or vehicle was given to C57BL/6 male mice for seven days before the occlusion of middle cerebral artery (MCAO) for 60min. High-resolution positron emission tomography scanner (micro-PET) was used for small animal imaging to examine glucose metabolism. Rota-rod time and neurological deficit scores were calculated after 24h of reperfusion. The volume of infarction was determined by Nissl-staining. The calpain proteolytic activity and eNOS uncoupling were determined by western blot analysis. SAA administration increased glucose metabolism and ameliorated neuronal damage after brain ischemia, paralleled with decreased neurological deficit and volume of infarction. In addition, SAA pretreatment inhibited eNOS uncoupling and calpain proteolytic activity. Furthermore, SAA inhibited peroxynitrite (ONOO - ) generation and upregulates AKT, FKHR and ERK phosphorylation. These findings strongly suggest that SAA elicits a neurovascular protective role through the inhibition of eNOS uncoupling and ONOO - formation. Moreover, SAA attenuates spectrin and calcineurin breakdown and therefore protects the brain against ischemic/reperfusion injury. Copyright © 2016 Elsevier GmbH. All rights reserved.

Draft Genome Sequence of Bacillus sp. GZT, a 2,4,6-Tribromophenol-Degrading Strain Isolated from the River Sludge of an Electronic Waste-Dismantling Region

PubMed Central

Liang, Zhishu; Li, Guiying; Das, Ranjit

2016-01-01

Here, we report the draft genome sequence of Bacillus sp. strain GZT, a 2,4,6-tribromophenol (TBP)-degrading bacterium previously isolated from an electronic waste-dismantling region. The draft genome sequence is 5.18 Mb and has a G+C content of 35.1%. This is the first genome report of a brominated flame retardant-degrading strain. PMID:27257197

Krikalev dismantles probe-and-cone docking mechanism (StM) in the Progress M-53 (18P)

NASA Image and Video Library

2005-06-19

ISS011-E-09204 (19 June 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, dismantles the probe-and-cone docking mechanism in the Progress 18 spacecraft. The Progress docked to the aft port of the Zvezda Service Module of the International Space Station (ISS) at 7:42 p.m. (CDT) as the Station flew approximately 225 statute miles, above a point near Beijing, China.

Heavy metal contamination characteristic of soil in WEEE (waste electrical and electronic equipment) dismantling community: a case study of Bangkok, Thailand.

PubMed

Damrongsiri, Seelawut; Vassanadumrongdee, Sujitra; Tanwattana, Puntita

2016-09-01

Sue Yai Utit is an old community located in Bangkok, Thailand which dismantles waste electrical and electronic equipment (WEEE). The surface soil samples at the dismantling site were contaminated with copper (Cu), lead (Pb), zinc (Zn), and nickel (Ni) higher than Dutch Standards, especially around the WEEE dumps. Residual fractions of Cu, Pb, Zn, and Ni in coarse soil particles were greater than in finer soil. However, those metals bonded to Fe-Mn oxides were considerably greater in fine soil particles. The distribution of Zn in the mobile fraction and a higher concentration in finer soil particles indicated its readily leachable character. The concentration of Cu, Pb, and Ni in both fine and coarse soil particles was mostly not significantly different. The fractionation of heavy metals at this dismantling site was comparable to the background. The contamination characteristics differed from pollution by other sources, which generally demonstrated the magnification of the non-residual fraction. A distribution pathway was proposed whereby contamination began by the deposition of WEEE scrap directly onto the soil surface as a source of heavy metal. This then accumulated, corroded, and was released via natural processes, becoming redistributed among the soil material. Therefore, the concentrations of both the residual and non-residual fractions of heavy metals in WEEE-contaminated soil increased.

Distribution of metals and brominated flame retardants (BFRs) in sediments, soils and plants from an informal e-waste dismantling site, South China.

PubMed

Wang, Junxia; Liu, Lili; Wang, Jinfu; Pan, Bishu; Fu, Xiaoxu; Zhang, Gang; Zhang, Long; Lin, Kuangfei

2015-01-01

Brominated flame retardants (BFRs, including polybrominated diphenyl ethers (PBDEs) and tetrabromobisphenol-A (TBBPA)) and metals (Cu, Zn, Pb, Cd, Ni, Hg and As) in sediments, soils and herb plants from unregulated e-waste disposal sites were examined. The metal concentrations, ∑PBDE and TBBPA concentrations in all samples from the examined e-waste dismantling sites were relatively high in comparison with those of rural and urban areas around the world. The PBDE and TBBPA levels in soils significantly decreased with increasing distance from the e-waste dismantling sites, indicating that PBDEs and TBBPA had similar transport potential from the e-waste dismantling process as a point source to the surrounding region. BDE-209 and TBBPA predominated in all samples, which is consistent with the evidence that the deca-BDE and TBBPA commercial mixtures were extensively used in electronic products. Metals, PBDEs and TBBPA displayed significant positive correlations with TOC, whereas the correlations with pH were insignificant, indicating that TOC was a major factor governing the spatial distribution, transportation and fate in sediments and soils. A significant relationship between log-transformed metals and BFR concentrations indicated common pollution sources. Moreover, cluster analysis and principal component analysis further confirmed that the metals and BFRs had a common source, and penta- and deca-BDE commercial products may be two sources of PBDEs in this region.

A literature review of studies using qualitative research to explore chronic neuromuscular disease.

PubMed

LaDonna, Kori A

2011-06-01

Although most neuromuscular disease research articles reflect traditional quantitative approaches, qualitative methods are becoming more prevalent in the neuromuscular literature. Arguably, qualitative research provides rich data that may be used to generate patient-centered outcome measures or influence current standards of care. The purpose of this article is to explore the qualitative literature pertaining to individuals and families living with chronic neuromuscular disease in order to suggest implications for practice. Fifty-six qualitative articles addressing seven research themes including Illness Experience; Work, Recreation, and Services; Assisted Ventilation; Caregiving; Genetics; Communication and Information Seeking; and Palliative Care were identified.

Neuromuscular adaptations to training, injury and passive interventions: implications for running economy.

PubMed

Bonacci, Jason; Chapman, Andrew; Blanch, Peter; Vicenzino, Bill

2009-01-01

Performance in endurance sports such as running, cycling and triathlon has long been investigated from a physiological perspective. A strong relationship between running economy and distance running performance is well established in the literature. From this established base, improvements in running economy have traditionally been achieved through endurance training. More recently, research has demonstrated short-term resistance and plyometric training has resulted in enhanced running economy. This improvement in running economy has been hypothesized to be a result of enhanced neuromuscular characteristics such as improved muscle power development and more efficient use of stored elastic energy during running. Changes in indirect measures of neuromuscular control (i.e. stance phase contact times, maximal forward jumps) have been used to support this hypothesis. These results suggest that neuromuscular adaptations in response to training (i.e. neuromuscular learning effects) are an important contributor to enhancements in running economy. However, there is no direct evidence to suggest that these adaptations translate into more efficient muscle recruitment patterns during running. Optimization of training and run performance may be facilitated through direct investigation of muscle recruitment patterns before and after training interventions. There is emerging evidence that demonstrates neuromuscular adaptations during running and cycling vary with training status. Highly trained runners and cyclists display more refined patterns of muscle recruitment than their novice counterparts. In contrast, interference with motor learning and neuromuscular adaptation may occur as a result of ongoing multidiscipline training (e.g. triathlon). In the sport of triathlon, impairments in running economy are frequently observed after cycling. This impairment is related mainly to physiological stress, but an alteration in lower limb muscle coordination during running after cycling has also been observed. Muscle activity during running after cycling has yet to be fully investigated, and to date, the effect of alterations in muscle coordination on running economy is largely unknown. Stretching, which is another mode of training, may induce acute neuromuscular effects but does not appear to alter running economy. There are also factors other than training structure that may influence running economy and neuromuscular adaptations. For example, passive interventions such as shoes and in-shoe orthoses, as well as the presence of musculoskeletal injury, may be considered important modulators of neuromuscular control and run performance. Alterations in muscle activity and running economy have been reported with different shoes and in-shoe orthoses; however, these changes appear to be subject-specific and non-systematic. Musculoskeletal injury has been associated with modifications in lower limb neuromuscular control, which may persist well after an athlete has returned to activity. The influence of changes in neuromuscular control as a result of injury on running economy has yet to be examined thoroughly, and should be considered in future experimental design and training analysis.

Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives.

PubMed

Carron, Michele; Bertoncello, Francesco; Ieppariello, Giovanna

2018-01-01

The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed.

Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives

PubMed Central

Carron, Michele; Bertoncello, Francesco; Ieppariello, Giovanna

2018-01-01

The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed. PMID:29317806

Evaluation of neuromuscular activity in patients with obstructive sleep apnea using chin surface electromyography of polysomnography.

PubMed

Yin, Guo-ping; Ye, Jing-ying; Han, De-min; Wang, Xiao-yi; Zhang, Yu-huan; Li, Yan-ru

2013-01-01

It is believed that defects in upper airway neuromuscular control play a role in sleep apnea pathogenesis. Currently, there is no simple and non-invasive method for evaluating neuromuscular activity for the purpose of screening in patients with obstructive sleep apnea. This study was designed to assess the validity of chin surface electromyography of routine polysomnography in evaluating the neuromuscular activity of obstructive sleep apnea subjects and probe the neuromuscular contribution in the pathogenesis of the condition. The chin surface electromyography of routine polysomnography during normal breathing and obstructive apnea were quantified in 36 male patients with obstructive sleep apnea. The change of chin surface electromyography from normal breathing to obstructive apnea was expressed as the percent compensated electromyography value, where the percent compensated electromyography value = (normal breath surface electromyography - apnea surface electromyography)/normal breath surface electromyography, and the percent compensated electromyography values among subjects were compared. The relationship between sleep apnea related parameters and the percent compensated electromyography value was examined. The percent compensated electromyography value of the subjects varied from 1% to 90% and had a significant positive correlation with apnea hypopnea index (R(2) = 0.382, P < 0.001). Recording and analyzing chin surface electromyography by routine polysomnography is a valid way of screening the neuromuscular activity in patients with obstructive sleep apnea. The neuromuscular contribution is different among subjects with obstructive sleep apnea.

Rationale and Clinical Techniques for Anterior Cruciate Ligament Injury Prevention Among Female Athletes

PubMed Central

Myer, Gregory D; Ford, Kevin R; Hewett, Timothy E

2004-01-01

Objective: To present the rationale and detailed techniques for the application of exercises targeted to prevent anterior cruciate ligament (ACL) injury in high-risk female athletes. Background: Female athletes have a 4- to 6-fold increased risk for ACL injury compared with their male counterparts playing at similar levels in the same sports. The increased ACL injury risk coupled with greater sports participation by young women over the last 30 years (9-fold increase in high school and 5-fold increase in collegiate sports) has generated public awareness and fueled several sex-related mechanistic and interventional investigations. These investigations provide the groundwork for the development of neuromuscular training aimed at targeting identified neuromuscular imbalances to decrease ACL injury risk. Description: After the onset of puberty, female athletes may not have a neuromuscular spurt to match their similar, rapid increase in growth and development. The lack of a natural neuromuscular adaptation may facilitate the development of neuromuscular imbalances that increase the risk for ACL injury. Dynamic neuromuscular analysis training provides the methodologic approach for identifying high-risk individuals and the basis of using interventions targeted to their specific needs. Clinical Advantages: Dynamic neuromuscular training applied to the high-risk population may decrease ACL injury risk and help more female athletes enjoy the benefits of sports participation without the long-term disabilities associated with injury. PMID:15592608

Achieving Effective Risk Management Reduction Throughout Decommissioning at the Columbus Closure Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, K.D.

2006-07-01

Nuclear facility decontamination, dismantlement, and demolition activities provide a myriad of challenges along the path to reaching a safe, effective, and compliant decommissioning. Among the challenges faced during decommissioning, is the constant management and technical effort to eliminate, mitigate, or minimize the potential of risks of radiation exposures and other hazards to the worker, the surrounding community, and the environment. Management strategies to eliminate, mitigate, or minimize risks include incorporating strong safety and As Low As Reasonably Achievable (ALARA) principles into an integrated work planning process. Technical and operational strategies may include utilizing predictive risk analysis tools to establish contaminationmore » limits for demolition and using remote handling equipment to reduce occupational and radiation exposures to workers. ECC and E2 Closure Services, LLC (Closure Services) have effectively utilized these management and technical tools to eliminate, mitigate, and reduce radiation exposures under contract to the U.S. Department of Energy (DOE) for the decontamination and decommissioning Columbus Closure Project (CCP). In particular, Closure Services achieved significant dose reduction during the dismantling, decontamination, and demolition activities for Building JN-1. Management strategies during the interior dismantlement, decontamination, and demolition of the facility demanded an integrated work planning processes that involved project disciplines. Integrated planning processes identified multiple opportunities to incorporate the use of remote handling equipment during the interior dismantling and demolition activities within areas of high radiation. Technical strategies employed predictive risk analysis tools to set upper bounding contamination limits, allowed for the radiological demolition of the building without exceeding administrative dose limits to the worker, general public, and the environment. Adhering to management and technical strategies during the dismantlement, decontamination, and demolition of Building JN-1 enabled Closure Services to achieve strong ALARA performance, maintain absolute compliance under the regulatory requirements and meeting licensing conditions for decommissioning. (authors)« less

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study

PubMed Central

Mathiesen, Ole; Hägi-Pedersen, Daniel; Skovgaard, Lene Theil; Østergaard, Doris; Engbaek, Jens; Gätke, Mona Ring

2017-01-01

Background Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. Objective The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff’s use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. Methods In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff’s knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. Results The e-learning module was implemented in 6 anesthesia departments on 21 November 2016. Currently, we are collecting postintervention data. The final dataset will include data from more than 10,000 anesthesia procedures. We expect to publish the results in late 2017 or early 2018. Conclusions With a dataset consisting of thousands of general anesthesia procedures, the INVERT study will assess whether an e-learning module can increase anesthetists’ use of neuromuscular monitoring. Trial Registration Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x) PMID:28986337

Prolonged administration of pyridostigmine impairs neuromuscular function with and without down-regulation of acetylcholine receptors.

PubMed

Richtsfeld, Martina; Yasuhara, Shingo; Fink, Heidrun; Blobner, Manfred; Martyn, J A Jeevendra

2013-08-01

The acetylcholinesterase inhibitor, pyridostigmine, is prophylactically administered to mitigate the toxic effects of nerve gas poisoning. The authors tested the hypothesis that prolonged pyridostigmine administration can lead to neuromuscular dysfunction and even down-regulation of acetylcholine receptors. Pyridostigmine (5 or 25 mg·kg·day) or saline was continuously administered via osmotic pumps to rats, and infused for either 14 or 28 days until the day of neuromuscular assessment (at day 14 or 28), or discontinued 24 h before neuromuscular assessment. Neurotransmission and muscle function were examined by single-twitch, train-of-four stimulation and 100-Hz tetanic stimulation. Sensitivity to atracurium and acetylcholine receptor number (quantitated by I-α-bungarotoxin) provided additional measures of neuromuscular integrity. Specific tetanic tensions (Newton [N]/muscle weight [g]) were significantly (P < 0.05) decreased at 14 (10.3 N/g) and 28 (11.1 N/g) days of 25 mg·kg·day pyridostigmine compared with controls (13.1-13.6 N/g). Decreased effective dose (0.81-1.05 vs. 0.16-0.45 mg/kg; P < 0.05) and decreased plasma concentration (3.02-3.27 vs. 0.45-1.37 μg/ml; P < 0.05) of atracurium for 50% paralysis (controls vs. 25 mg·kg·day pyridostigmine, respectively), irrespective of discontinuation of pyridostigmine, confirmed the pyridostigmine-induced altered neurotransmission. Pyridostigmine (25 mg·kg·day) down-regulated acetylcholine receptors at 28 days. Prolonged administration of pyridostigmine (25 mg·kg·day) leads to neuromuscular impairment, which can persist even when pyridostigmine is discontinued 24 h before assessment of neuromuscular function. Pyridostigmine has the potential to down-regulate acetylcholine receptors, but induces neuromuscular dysfunction even in the absence of receptor changes.

Corrective Neuromuscular Approach to the Treatment of Iliotibial Band Friction Syndrome: A Case Report

PubMed Central

Pettitt, Robert; Dolski, Angela

2000-01-01

Objective: To describe the evaluation and treatment process for inappropriate functional patterns of neuromuscular activity within the scope of an iliotibial band friction syndrome protocol. Background: Runners with iliotibial band friction syndrome are frequently fitted with orthotic devices to restrict excessive midfoot or rearfoot, or both, motions during the stance phase. These devices may fail to yield favorable results when underlying neuromuscular factors are associated with functional iliotibial band tightening. Differential Diagnosis: Distal biceps femoris tendinitis, popliteal tendinitis, lateral meniscus lesion. Treatment: The athlete's physical examination revealed several patterns of inappropriate neuromuscular activity attributed partly to the prolonged daily wear of beach-type sandals. Modifications of casual footwear and a temporary reduction in training volume were recommended initially to prevent exacerbation of the athlete's condition. Stretching, massage, and soft tissue mobilization were administered in accordance with the athlete's specific needs. The protocol included progressions of nonweightbearing and weightbearing therapeutic exercises. Neuromuscular electric stimulation was incorporated into the protocol to re-educate the role of the first ray within the stance phase of the athlete's walking gait. Uniqueness: Upon stationary examination, this athlete presented with normal lumbar and lower extremity postures. Gait analysis, however, revealed inappropriate dorsiflexion of the great toe during ambulation. Further, the athlete's performances on a series of tests to assess neuromuscular function were substandard. This athlete's response to previous treatment and unique physical findings required a corrective neuromuscular approach that deviates from iliotibial band friction syndrome protocols advocating the use of orthotics. Conclusions: While the role of any single treatment in the athlete's recovery remains unknown, it seems that a corrective neuromuscular approach in the management of iliotibial band friction syndrome represents a viable alternative to orthotic intervention. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5. PMID:16558617

Knee joint biomechanics and neuromuscular control during gait before and after total knee arthroplasty are sex-specific.

PubMed

Astephen Wilson, Janie L; Dunbar, Michael J; Hubley-Kozey, Cheryl L

2015-01-01

The future of total knee arthroplasty (TKA) surgery will involve planning that incorporates more patient-specific characteristics. Despite known biological, morphological, and functional differences between men and women, there has been little investigation into knee joint biomechanical and neuromuscular differences between men and women with osteoarthritis, and none that have examined sex-specific biomechanical and neuromuscular responses to TKA surgery. The objective of this study was to examine sex-associated differences in knee kinematics, kinetics and neuromuscular patterns during gait before and after TKA. Fifty-two patients with end-stage knee OA (28 women, 24 men) underwent gait and neuromuscular analysis within the week prior to and one year after surgery. A number of sex-specific differences were identified which suggest a different manifestation of end-stage knee OA between the sexes. Copyright © 2014 Elsevier Inc. All rights reserved.

The potential of disease management for neuromuscular hereditary disorders.

PubMed

Chouinard, Maud-Christine; Gagnon, Cynthia; Laberge, Luc; Tremblay, Carmen; Côté, Charlotte; Leclerc, Nadine; Mathieu, Jean

2009-01-01

Neuromuscular hereditary disorders require long-term multidisciplinary rehabilitation management. Although the need for coordinated healthcare management has long been recognized, most neuromuscular disorders are still lacking clinical guidelines about their long-term management and structured evaluation plan with associated services. One of the most prevalent adult-onset neuromuscular disorders, myotonic dystrophy type 1, generally presents several comorbidities and a variable clinical picture, making management a constant challenge. This article presents a healthcare follow-up plan and proposes a nursing case management within a disease management program as an innovative and promising approach. This disease management program and model consists of eight components including population identification processes, evidence-based practice guidelines, collaborative practice, patient self-management education, and process outcomes evaluation (Disease Management Association of America, 2004). It is believed to have the potential to significantly improve healthcare management for neuromuscular hereditary disorders and will prove useful to nurses delivering and organizing services for this population.

The role of proprioception and neuromuscular stability in carpal instabilities.

PubMed

Hagert, E; Lluch, A; Rein, S

2016-01-01

Carpal stability has traditionally been defined as dependent on the articular congruity of joint surfaces, the static stability maintained by intact ligaments, and the dynamic stability caused by muscle contractions resulting in a compression of joint surfaces. In the past decade, a fourth factor in carpal stability has been proposed, involving the neuromuscular and proprioceptive control of joints. The proprioception of the wrist originates from afferent signals elicited by sensory end organs (mechanoreceptors) in ligaments and joint capsules that elicit spinal reflexes for immediate joint stability, as well as higher order neuromuscular influx to the cerebellum and sensorimotor cortices for planning and executing joint control. The aim of this review is to provide an understanding of the role of proprioception and neuromuscular control in carpal instabilities by delineating the sensory innervation and the neuromuscular control of the carpus, as well as descriptions of clinical applications of proprioception in carpal instabilities. © The Author(s) 2015.

Effects of neuromuscular joint facilitation on bridging exercises with respect to deep muscle changes.

PubMed

Zhou, Bin; Huang, QiuChen; Zheng, Tao; Huo, Ming; Maruyama, Hitoshi

2015-05-01

[Purpose] This study examined the effects of neuromuscular joint facilitation on bridging exercises by assessing the cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis. [Subjects] Twelve healthy men. [Methods] Four exercises were evaluated: (a) supine resting, (b) bridging resistance exercise involving posterior pelvic tilting, (c) bridging resistance exercise involving anterior pelvic tilting, and (d) bridging resistance exercise involving neuromuscular joint facilitation. The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were measured during each exercise. [Results] The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were significantly greater in the neuromuscular joint facilitation group than the others. [Conclusion] Neuromuscular joint facilitation intervention improves the function of deep muscles such as the multifidus muscle and musculus transversus abdominis. Therefore, it can be recommended for application in clinical treatments such as that for back pain.

Comparison of treatment effect of neuromuscular electrical stimulation and thermal-tactile stimulation on patients with sub-acute dysphagia caused by stroke.

PubMed

Byeon, Haewon; Koh, Hyeung Woo

2016-06-01

[Purpose] The effectiveness of neuromuscular electrical stimulation in the rehabilitation of swallowing remains controversial. This study compared the effectiveness of neuromuscular electrical stimulation and thermal tactile oral stimulation, a traditional swallowing recovery treatment, in patients with sub-acute dysphagia caused by stroke. [Subjects and Methods] Subjects of the present study were 55 patients diagnosed with dysphagia caused by stroke. This study had a nonequivalent control group pretest-posttest design. [Results] Analysis of pre-post values of videofluoroscopic studies of the neuromuscular electrical stimulation and thermal tactile oral stimulation groups using a paired t-test showed no significant difference between the two groups despite both having decreased mean values of the videofluoroscopic studies after treatment. [Conclusion] This study's findings show that both neuromuscular electrical stimulation and thermal tactile oral stimulation significantly enhanced the swallowing function of patients with sub-acute dysphagia.

Comparison of treatment effect of neuromuscular electrical stimulation and thermal-tactile stimulation on patients with sub-acute dysphagia caused by stroke

PubMed Central

Byeon, Haewon; Koh, Hyeung Woo

2016-01-01

[Purpose] The effectiveness of neuromuscular electrical stimulation in the rehabilitation of swallowing remains controversial. This study compared the effectiveness of neuromuscular electrical stimulation and thermal tactile oral stimulation, a traditional swallowing recovery treatment, in patients with sub-acute dysphagia caused by stroke. [Subjects and Methods] Subjects of the present study were 55 patients diagnosed with dysphagia caused by stroke. This study had a nonequivalent control group pretest-posttest design. [Results] Analysis of pre-post values of videofluoroscopic studies of the neuromuscular electrical stimulation and thermal tactile oral stimulation groups using a paired t-test showed no significant difference between the two groups despite both having decreased mean values of the videofluoroscopic studies after treatment. [Conclusion] This study’s findings show that both neuromuscular electrical stimulation and thermal tactile oral stimulation significantly enhanced the swallowing function of patients with sub-acute dysphagia. PMID:27390421

Recycling scheme for scrapped automobiles in Japan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Masao; Nakajima, Akira; Taya, Sadao

Over 5 million cars are scrapped yearly in Japan. After dismantling scrapped automobiles, they are put into a shredder for differential recovery of ferrous and nonferrous metals. The residue, which is called shredder dust, runs over 1.2 million tons per year. This paper reports a entire sequence of scrapping cars in Japan with the following sections: (1) production and scrapped car management, (2) material composition, (3) dismantling, (4) shredder plant, (5) differential recovery of metals including specific gravity and newly developed color separation.

SIMULATED COAL GAS MCFC POWER PLANT SYSTEM VERIFICATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

J.A. Scroppo

1998-07-01

This is the Technical Progress Report covering June 1998. All tasks have been completed, except for those discussed on the following pages. Unocal estimated the costs of dismantling and packaging the test facility for storage and shipment. The scope of work for the contract has been modified to accommodate the dismantling and packaging of the plant. An amendment to Sub-Contract No. MCP-9-UNO between M-C Power and Unocal has been executed which includes the Scope of Work in Unocal's cost estimate.

SIMULATED COAL GAS MCFC POWER PLANT SYSTEM VERIFICATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1998-10-31

This is the Technical Progress Report covering October 1998. All tasks have been completed, except for those discussed on the following pages. Unocal estimated the costs of dismantling and packaging the test facility for storage and shipment. The scope of work for the contract has been modified to accommodate the dismantling and packaging of the plant. An amendment to Sub-Contract No. MCP-9-UNO between M-C Power and Unocal has been executed which includes the Scope of Work in Unocal's cost estimate.

Recent achievements in restorative neurology: Progressive neuromuscular diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

1986-01-01

This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies.

[Mechanisms of the therapeutic effect of bemitil in neuromuscular diseases].

PubMed

Lobzin, V S; Saĭkova, L A; Chukhlovina, M L; Pustozerov, V G

1991-01-01

Studies into the mechanism of the therapeutic action of bemitil were carried out in 21 patients with neuromuscular diseases. Measurements of lipid peroxidation and permeability of the erythrocytic membranes demonstrated the drug to influence carbohydrate and lipid metabolism, lipid peroxidation, and permeability of the cellular membranes. It is recommended that bemitil be used for the treatment of neuromuscular diseases.

Correspondence and challenges as neurologists to Kumamoto Earthquakes in 2016.

PubMed

Nakajima, Makoto; Nakane, Nozomi; Takamatsu, Kotaro; Yamashita, Satoshi; Nakane, Shunya; Yamashita, Taro; Ando, Yukio

2016-12-28

Kumamoto Earthquakes in 2016 severely affected medical circumstances and condition of each patient with neuro-muscular diseases, in addition to having destroyed life circumstances of local residence. Number of neuro-muscular disease patients admitted to the Department of Neurology, Kumamoto University, the only university hospital in the prefecture, increased approximately twice compared to usual years. Most of the related facilities were able to admit emergency patients with neuro-muscular diseases although the hospital buildings were damaged in various degrees. A number of issues remained unsolved as to emergency contact system, securement of emergency beds for severe neuro-muscular diseases, and information system for these patients.

Effects of neuromuscular electrostimulation in patients with heart failure admitted to ward.

PubMed

de Araújo, Carlos José Soares; Gonçalves, Fernanda Souza; Bittencourt, Hugo Souza; dos Santos, Noélia Gonçalves; Mecca Junior, Sérgio Vitor; Neves, Júlio Leal Bandeira; Fernandes, André Maurício Souza; Aras Junior, Roque; dos Reis, Francisco José Farias Borges; Guimarães, Armênio Costa; Rodrigues Junior, Erenaldo de Souza; Carvalho, Vitor Oliveira

2012-11-15

Neuromuscular electrostimulation has become a promising issue in cardiovascular rehabilitation. However there are few articles published in the literature regarding neuromuscular electrostimulation in patients with heart failure during hospital stay. This is a randomized controlled pilot trial that aimed to investigate the effect of neuromuscular electrostimulation in the walked distance by the six-minute walking test in 30 patients admitted to ward for heart failure treatment in a tertiary cardiology hospital. Patients in the intervention group performed a conventional rehabilitation and neuromuscular electrostimulation. Patients underwent 60 minutes of electrostimulation (wave frequency was 20 Hz, pulse duration of 20 us) two times a day for consecutive days until hospital discharge. The walked distance in the six-minute walking test improved 75% in the electrostimulation group (from 379.7 ± 43.5 to 372.9 ± 46.9 meters to controls and from 372.9 ± 62.4 to 500 ± 68 meters to electrostimulation, p<0.001). On the other hand, the walked distance in the control group did not change. The neuromuscular electrostimulation group showed greater improvement in the walked distance in the six-minute walking test in patients admitted to ward for compensation of heart failure.

Gender differences in offaxis neuromuscular control during stepping under a slippery condition.

PubMed

Lee, Song Joo; Ren, Yupeng; Geiger, François; Zhang, Li-Qun

2013-11-01

Females are at greater risks of musculoskeletal injuries than are males, which may be related to decreased neuromuscular control in axial and/or frontal planes, offaxis neuromuscular control. The objective of this study was to investigate gender differences in offaxis neuromuscular control during stepping under a slippery condition. Forty-three healthy subjects (21 males and 22 females) performed different stepping tasks under a slippery condition, namely, free pivoting task (FPT) to control axial plane pivoting, free sliding task (FST) to control frontal plane sliding, and free pivoting and sliding task (FPST) to control axial pivoting, and frontal sliding on a custom-made offaxis elliptical trainer. Compared to males, females showed significantly higher pivoting instability, higher max internal and external pivoting angles, higher mean max medial and lateral sliding distance, and higher entropy of time to peak EMG in the medial and lateral gastrocnemius muscles during the FPST and higher entropy of time to peak EMG in the lateral gastrocnemius muscle during the FPT and FST. The findings may help us understand potential injury risk factors associated with gender differences, and provide a basis for developing targeted neuromuscular training to improve offaxis neuromuscular control, and reduce musculoskeletal injuries associated with excessive offaxis loadings.

A discrete event simulation model of clinical and operating room efficiency outcomes of sugammadex versus neostigmine for neuromuscular block reversal in Canada.

PubMed

Insinga, Ralph P; Joyal, Cédric; Goyette, Alexandra; Galarneau, André

2016-11-16

The objective of this analysis is to explore potential impact on operating room (OR) efficiency and incidence of residual neuromuscular blockade (RNMB) with use of sugammadex (Bridion™, Merck & Co., Inc., Kenilworth, NJ USA) versus neostigmine for neuromuscular block reversal in Canada. A discrete event simulation (DES) model was developed to compare ORs using either neostigmine or sugammadex for NMB reversal over one month. Selected inputs included OR procedure and turnover times, hospital policies for paid staff overtime and procedural cancellations due to OR time over-run, and reductions in RNMB and associated complications with sugammadex use. Trials show sugammadex's impact on OR time and RNMB varies by whether full neuromuscular recovery (train-of-four ratio ≥0.9) is verified prior to extubation in the OR. Scenarios were therefore evaluated reflecting varied assumptions for neuromuscular reversal practices. With use of moderate neuromuscular block, when full neuromuscular recovery is verified prior to extubation (93 procedures performed with sugammadex, 91 with neostigmine), use of sugammadex versus neostigmine avoided 2.4 procedural cancellations due to OR time over-run and 33.5 h of paid staff overtime, while saving an average of 62 min per OR day. No difference was observed between comparators for these endpoints in the scenario when full neuromuscular recovery was not verified prior to extubation, however, per procedure risk of RNMB at extubation was reduced from 60% to 4% (reflecting 51 cases prevented), with associated reductions in risks of hypoxemia (12 cases avoided) and upper airway obstruction (23 cases avoided). Sugammadex impact in reversing deep neuromuscular block was evaluated in an exploratory analysis. When it was hypothetically assumed that 30 min of OR time were saved per procedure, the number of paid hours of staff over-time dropped from 84.1 to 32.0, with a 93% reduction in the per patient risk of residual blockade. In clinical practice within Canada, for the majority of patients currently managed with moderate neuromuscular block, the principal impact of substituting sugammadex for neostigmine is likely to be a reduction in the risk of residual blockade and associated complications. For patients maintained at a deep level of block to the end of the procedure, sugammadex is likely to both enhance OR efficiency and reduce residual block complications.

A novel amino acid and metabolomics signature in mice overexpressing muscle uncoupling protein 3

USDA-ARS?s Scientific Manuscript database

Uncoupling protein 3 (UCP3) is highly expressed in skeletal muscle and is known to lower mitochondrial reactive oxygen species and promote fatty acid oxidation; however, the global impact of UCP3 activity on skeletal muscle and whole body metabolism has not been extensively studied. We utilized unt...

MTORC1 Regulates both General Autophagy and Mitophagy Induction after Oxidative Phosphorylation Uncoupling.

PubMed

Bartolomé, Alberto; García-Aguilar, Ana; Asahara, Shun-Ichiro; Kido, Yoshiaki; Guillén, Carlos; Pajvani, Utpal B; Benito, Manuel

2017-09-11

The mechanistic target of rapamycin complex 1 (MTORC1) is a critical negative regulator of general autophagy. We hypothesized that MTORC1 may specifically regulate autophagic clearance of damaged mitochondria. To test this, we used cells lacking tuberous sclerosis complex 2 (TSC2 -/-), which show constitutive MTORC1 activation. TSC2 -/- cells show MTORC1-dependent impaired autophagic flux after chemical uncoupling of mitochondria, increased mitochondrial protein aging and accumulation of p62/SQSTM1 positive mitochondria. Mitochondrial autophagy (mitophagy) was also deficient in cells lacking TSC2, associated with altered expression of PTEN-induced kinase 1 (PINK1) and PARK2 translocation to uncoupled mitochondria, all of which were recovered by MTORC1 inhibition or expression of constitutively active FoxO1. These data prove the necessity of intact MTORC1 signaling to regulate two synergistic processes required for clearance of damaged mitochondria: 1) general autophagy initiation, and 2) PINK1/PARK2-mediated selective targeting of uncoupled mitochondria to the autophagic machinery. Copyright © 2017 American Society for Microbiology.

Carbon Tetrachloride at Hepatotoxic Levels Blocks Reversibly Gap Junctions between Rat Hepatocytes

NASA Astrophysics Data System (ADS)

Saez, J. C.; Bennett, M. V. L.; Spray, D. C.

1987-05-01

Electrical coupling and dye coupling between pairs of rat hepatocytes were reversibly reduced by brief exposure to halogenated methanes (CBrCl3, CCl4, and CHCl3). The potency of different halomethanes in uncoupling hepatocytes was comparable to their hepatotoxicity in vivo, and the rank order was the same as that of their tendency to form free radicals. The effect of carbon tetrachloride (CCl4) on hepatocytes was substantially reduced by prior treatment with SKF 525A, an inhibitor of cytochrome P-450, and by exposure to the reducing reagent β -mercaptoethanol. Halomethane uncoupling occurred with or without extracellular calcium and did not change intracellular concentrations of calcium and hydrogen ions or the phosphorylation state of the main gap-junctional protein. Thus the uncoupling appears to depend on cytochrome P-450 oxidative metabolism in which free radicals are generated and may result from oxidation of the gap-junctional protein or of a regulatory molecule that leads to closure of gap-junctional channels. Decreases in junctional conductance may be a rapid cellular response to injury that protects healthy cells by uncoupling them from unhealthy ones.

Nitric oxide, PKC-ε, and connexin43 are crucial for ischemic preconditioning-induced chemical gap junction uncoupling.

PubMed

Rong, Bing; Xie, Fei; Sun, Tao; Hao, Li; Lin, Ming-Jie; Zhong, Jing-Quan

2016-10-25

Ischemic preconditioning (IPC) maintains connexin43 (Cx43) phosphorylation and reduces chemical gap junction (GJ) coupling in cardiomyocytes to protect against ischemic damage. However, the signal transduction pathways underlying these effects are not fully understood. Here, we investigated whether nitric oxide (NO) and protein kinase C-ε (PKC-ε) contribute to IPC-induced cardioprotection by maintaining Cx43 phosphorylation and inhibiting chemical GJ coupling. IPC reduced ischemia-induced myocardial infarction and increased cardiomyocyte survival; phosphorylated Cx43, eNOS, and PKC-ε levels; and chemical GJ uncoupling. Administration of the NO donor SNAP mimicked the effects of IPC both in vivo and in vitro, maintaining Cx43 phosphorylation, promoting chemical GJ uncoupling, and reducing myocardial infarction. Preincubation with the NO synthase inhibitor L-NAME or PKC-ε translocation inhibitory peptide (PKC-ε-TIP) abolished these effects of IPC. Additionally, by inducing NO production, IPC induced translocation of PKC-ε, but not PKC-δ, from the cytosolic to the membrane fraction in primary cardiac myocytes. IPC-induced cardioprotection thus involves increased NO production, PKC-ε translocation, Cx43 phosphorylation, and chemical GJ uncoupling.

Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice.

PubMed

Li, B; Nolte, L A; Ju, J S; Han, D H; Coleman, T; Holloszy, J O; Semenkovich, C F

2000-10-01

To determine whether uncoupling respiration from oxidative phosphorylation in skeletal muscle is a suitable treatment for obesity and type 2 diabetes, we generated transgenic mice expressing the mitochondrial uncoupling protein (Ucp) in skeletal muscle. Skeletal muscle oxygen consumption was 98% higher in Ucp-L mice (with low expression) and 246% higher in Ucp-H mice (with high expression) than in wild-type mice. Ucp mice fed a chow diet had the same food intake as wild-type mice, but weighed less and had lower levels of glucose and triglycerides and better glucose tolerance than did control mice. Ucp-L mice were resistant to obesity induced by two different high-fat diets. Ucp-L mice fed a high-fat diet had less adiposity, lower levels of glucose, insulin and cholesterol, and an increased metabolic rate at rest and with exercise. They were also more responsive to insulin, and had enhanced glucose transport in skeletal muscle in the setting of increased muscle triglyceride content. These data suggest that manipulating respiratory uncoupling in muscle is a viable treatment for obesity and its metabolic sequelae.

Incredible negative values of effective electromechanical coupling coefficient for surface acoustic waves in piezoelectrics.

PubMed

Mozhaev, V G; Weihnacht, M

2000-07-01

The extraordinary case of increase in velocity of surface acoustic waves (SAW) caused by electrical shorting of the surface of the superstrong piezoelectric crystal potassium niobate, KNbO3, is numerically found. The explanation of this effect is based on considering SAWs as coupled Rayleigh and Bleustein-Gulyaev modes. A general procedure of approximate decoupling of the modes is suggested for piezoelectric crystals of arbitrary anisotropy. The effect under study takes place when the phase velocity of uncoupled sagittally polarized Rayleigh waves is intermediate between the phase velocities of uncoupled shear-horizontal Bleustein Gulyaev waves at the free and metallized surfaces. In this case, the metallization of the surface by an infinitely thin layer may cause a crossover of the velocity curves of the uncoupled waves. The presence of the mode coupling results in splitting of the curves with transition from one uncoupled branch to the other. This transition is responsible for the increase in SAW velocity, which appears to be greater than its common decrease produced by electrical shorting of the substrate surface.

Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.

PubMed

Tokuyama, Minami A; Xu, Cindy; Fisher, Rebecca E; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M

2018-01-15

Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response. Copyright © 2017 Elsevier Inc. All rights reserved.

Sugammadex given for rocuronium-induced neuromuscular blockade in infants: a retrospectıve study.

PubMed

Ozmete, Ozlem; Bali, Cagla; Cok, Oya Yalcin; Turk, Hatice Evren Eker; Ozyilkan, Nesrın Bozdogan; Civi, Soner; Aribogan, Anıs

2016-12-01

To evaluate the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in infant patients. Retrospective observational study. University teaching hospital. Twenty-six infants (2-12 months of age; 3-11 kg) with an American Society of Anesthesiologists classification I, II, or III who were scheduled to undergo neurosurgical procedures were included in the study. Anesthesia was induced with 5 mg/kg thiopental, 1 μg/kg fentanyl and 0.6 mg/kg rocuronium. Sevoflurane was administered to all patients after intubation. The neuromuscular block was monitored with acceleromyography using train-of-four (TOF) stimuli. Patients received additional doses of rocuronium to maintain a deep block during surgery. If profound neuromuscular block (TOF, 0) persisted at the end of the surgery, 3mg/kg sugammadex was administered. The demographic data, surgeries, and anesthetic agents were recorded. The time from sugammadex administration to recovery of neuromuscular function (TOF ratio, >0.9) and complications during and after extubation were also recorded. Twenty-six infants who had a deep neuromuscular block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in infant surgical patients for reversal of deep neuromuscular block induced by rocuronium. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Kun; Sun, Guoxun; Lv, Zhiyuan

Research highlights: {yields} Invertebrates, for example amphioxus, do express uncoupling proteins. {yields} Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. {yields} UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functionalmore » similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.« less

Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: a new mechanism.

PubMed

Leite, A Z; Sipahi, A M; Damião, A O; Coelho, A M; Garcez, A T; Machado, M C; Buchpiguel, C A; Lopasso, F P; Lordello, M L; Agostinho, C L; Laudanna, A A

2001-02-01

The pathogenesis of non-steroidal anti-inflammatory drug (NSAID) enteropathy is complex. It involves uncoupling of mitochondrial oxidative phosphorylation which alters the intercellular junction and increases intestinal permeability with consequent intestinal damage. Metronidazole diminishes the inflammation induced by indomethacin but the mechanisms remain speculative. A direct effect on luminal bacteria has traditionally been thought to account for the protective effect of metronidazole. However, a protective effect of metronidazole on mitochondrial oxidative phosphorylation has never been tested. To assess the protective effect of metronidazole on mitochondrial uncoupling induced by indomethacin and also on the increased intestinal permeability and macroscopic damage. The protective effect of metronidazole was evaluated in rats given indomethacin; a macroscopic score was devised to quantify intestinal lesions, and intestinal permeability was measured by means of (51)Cr-ethylenediaminetetraacetic acid. The protective effect of metronidazole against mitochondrial uncoupling induced by indomethacin was assessed using isolated coupled rat liver mitochondria obtained from rats pretreated with metronidazole or saline. Metronidazole significantly reduced the macroscopic intestinal damage and increase in intestinal permeability induced by indomethacin; furthermore, at the mitochondrial level, it significantly reduced the increase in oxygen consumption in state 4 induced by indomethacin and caused less reduction of the respiratory control rate. Our study confirmed the beneficial effects of metronidazole on intestinal damage and intestinal permeability, and demonstrated, for the first time, a direct protective effect of metronidazole on uncoupling of mitochondrial oxidative phosphorylation caused by NSAIDs.

Mitochondrial uncoupling, ROS generation and cardioprotection.

PubMed

Cadenas, Susana

2018-05-31

Mitochondrial oxidative phosphorylation is incompletely coupled, since protons translocated to the intermembrane space by specific respiratory complexes of the electron transport chain can return to the mitochondrial matrix independently of the ATP synthase -a process known as proton leak- generating heat instead of ATP. Proton leak across the inner mitochondrial membrane increases the respiration rate and decreases the electrochemical proton gradient (Δp), and is an important mechanism for energy dissipation that accounts for up to 25% of the basal metabolic rate. It is well established that mitochondrial superoxide production is steeply dependent on Δp in isolated mitochondria and, correspondingly, mitochondrial uncoupling has been identified as a cytoprotective strategy under conditions of oxidative stress, including diabetes, drug-resistance in tumor cells, ischemia-reperfusion (IR) injury or aging. Mitochondrial uncoupling proteins (UCPs) are able to lower the efficiency of oxidative phosphorylation and are involved in the control of mitochondrial reactive oxygen species (ROS) production. There is strong evidence that UCP2 and UCP3, the UCP1 homologues expressed in the heart, protect against mitochondrial oxidative damage by reducing the production of ROS. This review first analyzes the relationship between mitochondrial proton leak and ROS generation, and then focuses on the cardioprotective role of chemical uncoupling and uncoupling mediated by UCPs. This includes their protective effects against cardiac IR, a condition known to increase ROS production, and their roles in modulating cardiovascular risk factors such as obesity, diabetes and atherosclerosis. Copyright © 2018. Published by Elsevier B.V.

Temperature dependence of rat liver mitochondrial respiration with uncoupling of oxidative phosphorylation by fatty acids. Influence of inorganic phosphate.

PubMed

Samartsev, V N; Chezganova, S A; Polishchuk, L S; Paydyganov, A P; Vidyakina, O V; Zeldi, I P

2003-06-01

The respiration rate of liver mitochondria in the course of succinate oxidation depends on temperature in the presence of palmitate more strongly than in its absence (in state 4). In the Arrhenius plot, the temperature dependence of the palmitate-induced stimulation of respiration has a bend at 22 degrees C which is characterized by transition of the activation energy from 120 to 60 kJ/mol. However, a similar dependence of respiration in state 4 is linear over the whole temperature range and corresponds to the activation energy of 17 kJ/mol. Phosphate partially inhibits the uncoupling effect of palmitate. This effect of phosphate is increased on decrease in temperature. In the presence of phosphate the temperature dependence in the Arrhenius plot also has a bend at 22 degrees C, and the activation energy increases from 128 to 208 kJ/mol in the range from 13 to 22 degrees C and from 56 to 67 kJ/mol in the range from 22 to 37 degrees C. Mersalyl (10 nmol/mg protein), an inhibitor of the phosphate carrier, similarly to phosphate, suppresses the uncoupling effect of laurate, and the effects of mersalyl and phosphate are not additive. The recoupling effects of phosphate and mersalyl seem to show involvement of the phosphate carrier in the uncoupling effect of fatty acids in liver mitochondria. Possible mechanisms of involvement of the phosphate carrier in the uncoupling effect of fatty acids are discussed.

SR4 Uncouples Mitochondrial Oxidative Phosphorylation, Modulates AMP-dependent Kinase (AMPK)-Mammalian Target of Rapamycin (mTOR) Signaling, and Inhibits Proliferation of HepG2 Hepatocarcinoma Cells.

PubMed

Figarola, James L; Singhal, Jyotsana; Tompkins, Joshua D; Rogers, George W; Warden, Charles; Horne, David; Riggs, Arthur D; Awasthi, Sanjay; Singhal, Sharad S

2015-12-18

Mitochondrial oxidative phosphorylation produces most of the energy in aerobic cells by coupling respiration to the production of ATP. Mitochondrial uncouplers, which reduce the proton gradient across the mitochondrial inner membrane, create a futile cycle of nutrient oxidation without generating ATP. Regulation of mitochondrial dysfunction and associated cellular bioenergetics has been recently identified as a promising target for anticancer therapy. Here, we show that SR4 is a novel mitochondrial uncoupler that causes dose-dependent increase in mitochondrial respiration and dissipation of mitochondrial membrane potential in HepG2 hepatocarcinoma cells. These effects were reversed by the recoupling agent 6-ketocholestanol but not cyclosporin A and were nonexistent in mitochondrial DNA-depleted HepG2 cells. In isolated mouse liver mitochondria, SR4 similarly increased oxygen consumption independent of adenine nucleotide translocase and uncoupling proteins, decreased mitochondrial membrane potential, and promoted swelling of valinomycin-treated mitochondria in potassium acetate medium. Mitochondrial uncoupling in HepG2 cells by SR4 results in the reduction of cellular ATP production, increased ROS production, activation of the energy-sensing enzyme AMPK, and inhibition of acetyl-CoA carboxylase and mammalian target of rapamycin signaling pathways, leading to cell cycle arrest and apoptosis. Global analysis of SR4-associated differential gene expression confirms these observations, including significant induction of apoptotic genes and down-regulation of cell cycle, mitochondrial, and oxidative phosphorylation pathway transcripts at 24 h post-treatment. Collectively, our studies demonstrate that the previously reported indirect activation of AMPK and in vitro anticancer properties of SR4 as well as its beneficial effects in both animal xenograft and obese mice models could be a direct consequence of its mitochondrial uncoupling activity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Hypercholesterolemia-induced erectile dysfunction: endothelial nitric oxide synthase (eNOS) uncoupling in the mouse penis by NAD(P)H oxidase

PubMed Central

Musicki, Biljana; Liu, Tongyun; Lagoda, Gwen A.; Strong, Travis D.; Sezen, Sena F.; Johnson, Justin M.; Burnett, Arthur L.

2010-01-01

INTRODUCTION Hypercholesterolemia induces erectile dysfunction (ED) mostly by increasing oxidative stress and impairing endothelial function in the penis, but the mechanisms regulating reactive oxygen species (ROS) production in the penis are not understood. AIMS We evaluated whether hypercholesterolemia activates nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the penis, providing an initial source of ROS to induce endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction resulting in ED. METHODS Low-density-lipoprotein receptor (LDLR)–null mice were fed Western diet for 4 weeks to induce early-stage hyperlipidemia. Wild type (WT) mice fed regular chow served as controls. Mice received NAD(P)H oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Erectile function was assessed in response to cavernous nerve electrical stimulation. Markers of endothelial function (phospho [P]-vasodilator-stimulated-protein [VASP]-Ser-239), oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NAD[P]H oxidase subunits p67phox, p47phox, and gp91phox), P-eNOS-Ser-1177, and eNOS were measured by Western blot in penes. MAIN OUTCOME MEASURES Molecular mechanisms of ROS generation and endothelial dysfunction in hypercholesterolemia-induced ED. RESULTS Erectile response was significantly (P<0.05) reduced in hypercholesterolemic LDLR-null mice compared to WT mice. Relative to WT mice, hypercholesterolemia increased (P<0.05) protein expressions of NAD(P)H oxidase subunits p67phox, p47phox and gp91phox, eNOS uncoupling, and 4-HNE-modified proteins, and reduced (P<0.05) P-VASP-Ser-239 expression in the penis. Apocynin treatment of LDLR-null mice preserved (P<0.05) maximal intracavernosal pressure, and reversed (P < 0.05) the abnormalities in protein expressions of gp67phox and gp47phox, 4-HNE, P-VASP-Ser-239, and eNOS uncoupling in the penis. Apocynin treatment of WT mice did not affect any of these parameters. Protein expressions of P-eNOS-Ser-1177 and total eNOS were unaffected by hypercholesterolemia. CONCLUSION Activated NAD(P)H oxidase in the penis is an initial source of oxidative stress resulting in eNOS uncoupling, thus providing a mechanism of eNOS uncoupling and endothelial dysfunction in hypercholesterolemia-induced ED. PMID:20626609

Generation and detection of metal ions and volatile organic compounds (VOCs) emissions from the pretreatment processes for recycling spent lithium-ion batteries.

PubMed

Li, Jia; Wang, Guangxu; Xu, Zhenming

2016-06-01

The recycling of spent lithium-ion batteries brings benefits to both economic and environmental terms, but it can also lead to contaminants in a workshop environment. This study focused on metals, non-metals and volatile organic compounds generated by the discharging and dismantling pretreatment processes which are prerequisite for recycling spent lithium-ion batteries. After discharging in NaCl solution, metal contents in supernate and concentrated liquor were detected. Among results of condition #2, #3, #4 and #5, supernate and concentrated liquor contain high levels of Na, Al, Fe; middle levels of Co, Li, Cu, Ca, Zn; and low levels of Mn, Sn, Cr, Zn, Ba, K, Mg, V. The Hg, Ag, Cr and V are not detected in any of the analyzed supernate. 10wt% NaCl solution was a better discharging condition for high discharge efficiency, less possible harm to environment. To collect the gas released from dismantled LIB belts, a set of gas collecting system devices was designed independently. Two predominant organic vapour compounds were dimethyl carbonate (4.298mgh(-1)) and tert-amylbenzene (0.749mgh(-1)) from one dismantled battery cell. To make sure the concentrations of dimethyl carbonate under recommended industrial exposure limit (REL) of 100mgL(-1), for a workshop on dismantling capacity of 1000kg spent LIBs, the minimum flow rate of ventilating pump should be 235.16m(3)h(-1). Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area.

PubMed

Yang, Yan; Lu, Xiao Song; Li, Ding Long; Yu, Yun Jiang

2013-06-01

To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels. An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied. The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks. There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Hazardous substances in indoor dust emitted from waste TV recycling facility.

PubMed

Deng, Jingjing; Guo, Jie; Zhou, Xiaoyu; Zhou, Peng; Fu, Xiaoxu; Zhang, Wei; Lin, Kuangfei

2014-06-01

Various hazardous substances contained in waste TV sets might be released into environment via dust during recycling activities. Two brominated flame retardants (BFRs), polybrominated diphenyl ethers (PBDEs), and tetrabromobisphenol A (TBBPA), and five kinds of heavy metals (Cu, Pb, Cd, Cr, and Ni) were detected in indoor dust collected from two workshops (TV dismantling workshop and subsequent recycling workshop). PBDEs concentrations in dust from waste wires recycling line (722,000 ng/g) were the highest among the studied sites, followed by those in manual dismantling-sorting line (117,000 ng/g), whereas TBBPA concentrations were the highest in manual dismantling-sorting line (557 ng/g) and printed circuit board (PCB) recycling line (428 ng/g). For heavy metals, Cu and Pb were the most enriched metals in all dust samples. The highest concentration of Pb (22,900 mg/kg) was found in TV dismantling workshop-floor dust. Meanwhile, Cu was the predominant metal in dust from the PCB recycling line, especially in dust collected from electrostatic separation area (42,700 mg/kg). Occupational exposure assessment results showed that workers were the most exposed to BDE-209 among the four PBDE congeners (BDE-47, BDE-99, BDE-153, and BDE-209) in both workshops. The hazard quotient (HQ) indicated that noncancerous effects were unlikely for both BFRs and heavy metals (HQ < 1), and carcinogenic risks for Cd, Cr, and Ni (risk < 10(-6)) on workers in two workshops were relatively low.

Diagnostic support for selected neuromuscular diseases using answer-pattern recognition and data mining techniques: a proof of concept multicenter prospective trial.

PubMed

Grigull, Lorenz; Lechner, Werner; Petri, Susanne; Kollewe, Katja; Dengler, Reinhard; Mehmecke, Sandra; Schumacher, Ulrike; Lücke, Thomas; Schneider-Gold, Christiane; Köhler, Cornelia; Güttsches, Anne-Katrin; Kortum, Xiaowei; Klawonn, Frank

2016-03-08

Diagnosis of neuromuscular diseases in primary care is often challenging. Rare diseases such as Pompe disease are easily overlooked by the general practitioner. We therefore aimed to develop a diagnostic support tool using patient-oriented questions and combined data mining algorithms recognizing answer patterns in individuals with selected neuromuscular diseases. A multicenter prospective study for the proof of concept was conducted thereafter. First, 16 interviews with patients were conducted focusing on their pre-diagnostic observations and experiences. From these interviews, we developed a questionnaire with 46 items. Then, patients with diagnosed neuromuscular diseases as well as patients without such a disease answered the questionnaire to establish a database for data mining. For proof of concept, initially only six diagnoses were chosen (myotonic dystrophy and myotonia (MdMy), Pompe disease (MP), amyotrophic lateral sclerosis (ALS), polyneuropathy (PNP), spinal muscular atrophy (SMA), other neuromuscular diseases, and no neuromuscular disease (NND). A prospective study was performed to validate the automated malleable system, which included six different classification methods combined in a fusion algorithm proposing a final diagnosis. Finally, new diagnoses were incorporated into the system. In total, questionnaires from 210 individuals were used to train the system. 89.5 % correct diagnoses were achieved during cross-validation. The sensitivity of the system was 93-97 % for individuals with MP, with MdMy and without neuromuscular diseases, but only 69 % in SMA and 81 % in ALS patients. In the prospective trial, 57/64 (89 %) diagnoses were predicted correctly by the computerized system. All questions, or rather all answers, increased the diagnostic accuracy of the system, with the best results reached by the fusion of different classifier methods. Receiver operating curve (ROC) and p-value analyses confirmed the results. A questionnaire-based diagnostic support tool using data mining methods exhibited good results in predicting selected neuromuscular diseases. Due to the variety of neuromuscular diseases, additional studies are required to measure beneficial effects in the clinical setting.

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study.

PubMed

Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel; Skovgaard, Lene Theil; Østergaard, Doris; Engbaek, Jens; Gätke, Mona Ring

2017-10-06

Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. The e-learning module was implemented in 6 anesthesia departments on 21 November 2016. Currently, we are collecting postintervention data. The final dataset will include data from more than 10,000 anesthesia procedures. We expect to publish the results in late 2017 or early 2018. With a dataset consisting of thousands of general anesthesia procedures, the INVERT study will assess whether an e-learning module can increase anesthetists' use of neuromuscular monitoring. Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x). ©Jakob Louis Demant Thomsen, Ole Mathiesen, Daniel Hägi-Pedersen, Lene Theil Skovgaard, Doris Østergaard, Jens Engbaek, Mona Ring Gätke. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 06.10.2017.

Relationship between expression of muscle-specific uncoupling protein 2 messenger RNA and genetic selection toward growth in channel catfish

USDA-ARS?s Scientific Manuscript database

Uncoupling protein 2 is a member of the mitochondrial channel proteins that regulate the flow of hydrogen ions and ATP generation. The relationship between UCP2 and nutrient metabolism has been well-defined in humans but unclear in fish. We hypothesized that increased muscle growth in channel catf...

Mode detuning in systems of weakly coupled oscillators

NASA Astrophysics Data System (ADS)

Spencer, Ross L.; Robertson, Richard D.

2001-11-01

A system of weakly magnetically coupled oscillating blades is studied experimentally, computationally, and theoretically. It is found that when the uncoupled natural frequencies of the blades are nearly equal, the normal modes produced by the coupling are almost impossible to find experimentally if the random variation level in the system parameters is on the order of (or larger than) the relative differences between mode frequencies. But if the uncoupled natural frequencies are made to vary (detuned) in a smooth way such that the total relative spread in natural frequency exceeds the random variations, normal modes are rather easy to find. And if the detuned uncoupled frequencies of the system are parabolically distributed, the modes are found to be shaped like Hermite functions.

Solving Modal Equations of Motion with Initial Conditions Using MSC/NASTRAN DMAP. Part 2; Coupled Versus Uncoupled Integration

NASA Technical Reports Server (NTRS)

Barnett, Alan R.; Ibrahim, Omar M.; Abdallah, Ayman A.; Sullivan, Timothy L.

1993-01-01

By utilizing MSC/NASTRAN DMAP (Direct Matrix Abstraction Program) in an existing NASA Lewis Research Center coupled loads methodology, solving modal equations of motion with initial conditions is possible using either coupled (Newmark-Beta) or uncoupled (exact mode superposition) integration available within module TRD1. Both the coupled and newly developed exact mode superposition methods have been used to perform transient analyses of various space systems. However, experience has shown that in most cases, significant time savings are realized when the equations of motion are integrated using the uncoupled solver instead of the coupled solver. Through the results of a real-world engineering analysis, advantages of using the exact mode superposition methodology are illustrated.

The epidemiology of neuromuscular disorders: Age at onset and gender in the Netherlands.

PubMed

Deenen, Johanna C W; van Doorn, Pieter A; Faber, Catharina G; van der Kooi, Anneke J; Kuks, Jan B M; Notermans, Nicolette C; Visser, Leo H; Horlings, Corinne G C; Verschuuren, Jan J G M; Verbeek, André L M; van Engelen, Baziel G M

2016-07-01

Based on approximately eight years of data collection with the nationwide Computer Registry of All Myopathies and Polyneuropathies (CRAMP) in the Netherlands, recent epidemiologic information for thirty neuromuscular disorders is presented. This overview includes age and gender data for a number of neuromuscular disorders that are either relatively frequently seen in the neuromuscular clinic, or have a particular phenotype. Since 2004, over 20,000 individuals with a neuromuscular disorder were registered in CRAMP; 56% men and 44% women. The number per diagnosis varied from nine persons with Emery-Dreifuss muscular dystrophy to 2057 persons with amyotrophic lateral sclerosis. Proportions of men ranged from 38% with post-polio syndrome to 68% with progressive spinal muscular atrophy, excluding X-chromosome linked disorders. Inclusion body myositis showed the highest median age at diagnosis of 70 years. These data may be helpful in the diagnostic process in clinical practice and trial readiness. Copyright © 2016 Elsevier B.V. All rights reserved.

The relative frequency of common neuromuscular diagnoses in a reference center.

PubMed

Cotta, Ana; Paim, Júlia Filardi; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Navarro, Monica M; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier-Neto, Rafael; Baptista, Sidney; Lima, Luciano Romero; Takata, Reinaldo Issao; Vargas, Antonio Pedro

2017-11-01

The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. To report the relative frequency of common neuromuscular diagnoses in a reference center. A 17-year chart review of patients with suspicion of myopathy. Among 3,412 examinations, 1,603 (46.98%) yielded confirmatory results: 782 (48.78%) underwent molecular studies, and 821 (51.21%) had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%), mitochondriopathy 330 (20.59%), spinal muscular atrophy 158 (9.86%), limb girdle muscular dystrophy 157 (9.79%), Steinert myotonic dystrophy 138 (8.61%), facioscapulohumeral muscular dystrophy 99 (6.17%), and other diagnoses 261 (16.28%). Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.

Diagnostic histochemistry and clinical-pathological testings as molecular pathways to pathogenesis and treatment of the ageing neuromuscular system: a personal view.

PubMed

Engel, W King

2015-04-01

Ageing of the neuromuscular system in elderhood ingravescently contributes to slowness, weakness, falling and death, often accompanied by numbness and pain. This article is to put in perspective examples from a half-century of personal and team neuromuscular histochemical-pathological and clinical-pathological research, including a number of lucky and instructive accomplishments identifying new treatments and new diseases. A major focus currently is on some important, still enigmatic, aspects of the ageing neuromuscular system. It is also includes some of the newest references of others on various closely-related aspects of this ageing system. The article may help guide others in their molecular-based endeavors to identify paths leading to discovering new treatments and new pathogenic aspects. These are certainly needed - our ageing and unsteady constituents are steadily increasing. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy

PubMed Central

Kim, Ji Eun; Chun, Hea Rim

2017-01-01

Abstract Introduction: Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. Clinical features: An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. Conclusion: A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD. PMID:28353578

Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy: A case Report.

PubMed

Kim, Ji Eun; Chun, Hea Rim

2017-03-01

Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD.

A computer-controlled, closed-loop infusion system for infusing muscle relaxants: its use during motor-evoked potential monitoring.

PubMed

Stinson, L W; Murray, M J; Jones, K A; Assef, S J; Burke, M J; Behrens, T L; Lennon, R L

1994-02-01

A microcomputer-controlled closed-loop infusion system (MCCLIS) has been developed that provides stable intraoperative levels of partial neuromuscular blockade. Complete neuromuscular blockade interferes with intraoperative motor-evoked potential (MEP) monitoring used for patients undergoing surgical procedures that place them at risk for spinal cord ischemia. Nine patients were studied during which the MCCLIS maintained stable levels of partial neuromuscular blockade and allowed transcranial magnetic motor-evoked potential (TcM-MEP) monitoring during thoracoabdominal aortic aneurysmectomy. The use of TcM-MEP for monitoring intraoperative spinal cord function was balanced against surgical considerations for muscle relaxation with 80% to 90% neuromuscular blockade fulfilling each requirement. Intraoperative adjustment of partial neuromuscular blockade to facilitate TcM-MEP monitoring was also possible with the MCCLIS. The MCCLIS should allow for further investigation into the sensitivity, specificity, and predictability of TcM-MEP monitoring for any patient at risk for intraoperative spinal cord ischemia including those undergoing thoracoabdominal aortic aneurysmectomy.

An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

PubMed Central

Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

2014-01-01

Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

Effect of the Masako maneuver and neuromuscular electrical stimulation on the improvement of swallowing function in patients with dysphagia caused by stroke

PubMed Central

Byeon, Haewon

2016-01-01

[Purpose] The aim of this study was to compare improvements in swallowing function by the intervention of the Masako maneuver and neuromuscular electrical stimulation in patients with dysphagia caused by stroke. [Subjects and Methods] The Masako maneuver (n=23) and neuromuscular electrical stimulation (n=24) were conducted in 47 patients with dysphagia caused by stroke over a period of 4 weeks. Swallowing recovery was recorded using the functional dysphagia scale based on videofluoroscopic studies. [Results] Mean functional dysphagia scale values for the Masako maneuver and neuromuscular electrical stimulation groups decreased after the treatments. However, the pre-post functional dysphagia scale values showed no statistically significant differences between the groups. [Conclusion] The Masako maneuver and neuromuscular electrical stimulation each showed significant effects on the improvement of swallowing function for the patients with dysphagia caused by stroke, but no significant difference was observed between the two treatment methods. PMID:27512266

Neuromuscular transmission failure in myasthenia gravis: decrement of safety factor and susceptibility of extraocular muscles.

PubMed

Serra, Alessandro; Ruff, Robert L; Leigh, Richard John

2012-12-01

An appropriate density of acetylcholine receptors (AChRs) and Na(+) channels (NaChs) in the normal neuromuscular junction (NMJ) determines the magnitude of safety factor (SF) that guarantees fidelity of neuromuscular transmission. In myasthenia gravis (MG), an overall simplification of the postsynaptic folding secondary to NMJ destruction results in AChRs and NaChs depletion. Loss of AChRs and NaChs accounts, respectively, for 59% and 40% reduction of the SF at the endplate, which manifests as neuromuscular transmission failure. The extraocular muscles (EOM) have physiologically less developed postsynaptic folding, hence a lower baseline SF, which predisposes them to dysfunction in MG and development of fatigue during "high performance" eye movements, such as saccades. However, saccades in MG show stereotyped, conjugate initial components, similar to normal, which might reflect preserved neuromuscular transmission fidelity at the NMJ of the fast, pale global fibers, which have better developed postsynaptic folding than other extraocular fibers. © 2012 New York Academy of Sciences.

Swallowing and Secretion Management in Neuromuscular Disease.

PubMed

Britton, Deanna; Karam, Chafic; Schindler, Joshua S

2018-06-01

Neuromuscular disease frequently leads to dysphagia and difficulty managing secretions. Dysphagia may lead to medical complications, such as malnutrition, dehydration, aspiration pneumonia, and other pulmonary complications, as well as social isolation and reduced overall quality of life. This review provides an overview of dysphagia associated with neuromuscular disease in adults, along with a concise review of swallowing assessment and intervention options. Copyright © 2018 Elsevier Inc. All rights reserved.

Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

PubMed

Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

2016-06-01

Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders.

PubMed

Camacho, A; Esteban, J; Paradas, C

A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. Our group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. Neuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The Role of Neuromuscular Changes in Aging and Knee Osteoarthritis on Dynamic Postural Control

PubMed Central

Takacs, Judit; Carpenter, Mark G.; Garland, S. Jayne; Hunt, Michael A.

2013-01-01

Knee osteoarthritis (OA) is a chronic joint condition, with 30% of those over the age of 75 exhibiting severe radiographic disease. Nearly 50% of those with knee OA have experienced a fall in the past year. Falls are a considerable public health concern, with a high risk of serious injury and a significant socioeconomic impact. The ability to defend against a fall relies on adequate dynamic postural control, and alterations in dynamic postural control are seen with normal aging. Neuromuscular changes associated with aging may be responsible for some of these alterations in dynamic postural control. Even greater neuromuscular deficits, which may impact dynamic postural control and the ability to defend against a fall, are seen in people with knee OA. There is little evidence to date on how knee OA affects the ability to respond to and defend against falls and the neuromuscular changes that contribute to balance deficits. As a result, this review will: summarize the key characteristics of postural responses to an external perturbation, highlight the changes in dynamic postural control seen with normal aging, review the neuromuscular changes associated with aging that have known and possible effects on dynamic postural control, and summarize the neuromuscular changes and balance problems in knee OA. Future research to better understand the role of neuromuscular changes in knee OA and their effect on dynamic postural control will be suggested. Such an understanding is critical to the successful creation and implementation of fall prevention and treatment programs, in order to reduce the excessive risk of falling in knee OA. PMID:23696951

Robotic assessment of neuromuscular characteristics using musculoskeletal models: A pilot study.

PubMed

Jayaneththi, V R; Viloria, J; Wiedemann, L G; Jarrett, C; McDaid, A J

2017-07-01

Non-invasive neuromuscular characterization aims to provide greater insight into the effectiveness of existing and emerging rehabilitation therapies by quantifying neuromuscular characteristics relating to force production, muscle viscoelasticity and voluntary neural activation. In this paper, we propose a novel approach to evaluate neuromuscular characteristics, such as muscle fiber stiffness and viscosity, by combining robotic and HD-sEMG measurements with computational musculoskeletal modeling. This pilot study investigates the efficacy of this approach on a healthy population and provides new insight on potential limitations of conventional musculoskeletal models for this application. Subject-specific neuromuscular characteristics of the biceps and triceps brachii were evaluated using robot-measured kinetics, kinematics and EMG activity as inputs to a musculoskeletal model. Repeatability experiments in five participants revealed large variability within each subjects evaluated characteristics, with almost all experiencing variation greater than 50% of full scale when repeating the same task. The use of robotics and HD-sEMG, in conjunction with musculoskeletal modeling, to quantify neuromuscular characteristics has been explored. Despite the ability to predict joint kinematics with relatively high accuracy, parameter characterization was inconsistent i.e. many parameter combinations gave rise to minimal kinematic error. The proposed technique is a novel approach for in vivo neuromuscular characterization and is a step towards the realization of objective in-home robot-assisted rehabilitation. Importantly, the results have confirmed the technical (robot and HD-sEMG) feasibility while highlighting the need to develop new musculoskeletal models and optimization techniques capable of achieving consistent results across a range of dynamic tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of routine reversal of neuromuscular blockade on adequacy of recurrent laryngeal nerve stimulation during thyroid surgery.

PubMed

Marshall, S D; Boden, E; Serpell, J

2015-07-01

Testing of the integrity of the recurrent laryngeal nerve during thyroid surgery has become routine practice for many surgeons to aid dissection and minimise the chance of inadvertent nerve injury. We hypothesised that routine reversal of an intermediate-acting, non-depolarising neuromuscular blocking agent would improve conditions for stimulation of the recurrent laryngeal nerve. We conducted a single-centre, randomised, double-blind placebo-controlled trial of patients undergoing thyroid surgery by the same surgeon. After randomisation, the participants received either neostigmine 2.5 mg with glycopyrrolate 0.4 mg or placebo, at 30 minutes after induction of anaesthesia and administration of 0.4 mg/kg of atracurium. The primary outcome was the subjective assessment by the surgeon as to whether the neuromuscular function was adequate for stimulation of the recurrent laryngeal nerve using a neuromuscular integrity monitor (NIM). Time to NIM stimulation was 44.6 minutes in the placebo group and 41.4 minutes in the intervention group (P=0.268). Of the 21 patients who received the neuromuscular blockade reversal, 20 (95.2%) had adequate surgical conditions for NIM stimulation, compared to 9 out of 18 patients (50%) in the placebo group (P=0.002). Three of the ten patients (30%) with inadequate reversal showed no evidence of residual blockade assessed peripherally. The routine reversal of neuromuscular blockade at 30 minutes post induction appears to result in adequate surgical conditions for safe stimulation of the recurrent laryngeal nerve. Return of neuromuscular function at a peripheral site does not guarantee adequate laryngeal muscle function for use of the NIM.

The impact of neuromuscular electrical stimulation on recovery after intensive, muscle damaging, maximal speed training in professional team sports players.

PubMed

Taylor, Tom; West, Daniel J; Howatson, Glyn; Jones, Chris; Bracken, Richard M; Love, Thomas D; Cook, Christian J; Swift, Eamon; Baker, Julien S; Kilduff, Liam P

2015-05-01

During congested fixture periods in team sports, limited recovery time and increased travel hinder the implementation of many recovery strategies; thus alternative methods are required. We examined the impact of a neuromuscular electrical stimulation device on 24-h recovery from an intensive training session in professional players. Twenty-eight professional rugby and football academy players completed this randomised and counter-balanced study, on 2 occasions, separated by 7 days. After baseline perceived soreness, blood (lactate and creatine kinase) and saliva (testosterone and cortisol) samples were collected, players completed a standardised warm-up and baseline countermovement jumps (jump height). Players then completed 60 m × 50 m maximal sprints, with 5 min recovery between efforts. After completing the sprint session, players wore a neuromuscular electrical stimulation device or remained in normal attire (CON) for 8 h. All measures were repeated immediately, 2 and 24-h post-sprint. Player jump height was reduced from baseline at all time points under both conditions; however, at 24-h neuromuscular electrical stimulation was significantly more recovered (mean±SD; neuromuscular electrical stimulation -3.2±3.2 vs. CON -7.2±3.7%; P<0.001). Creatine kinase concentrations increased at all time points under both conditions, but at 24-h was lower under neuromuscular electrical stimulation (P<0.001). At 24-h, perceived soreness was significantly lower under neuromuscular electrical stimulation, when compared to CON (P=0.02). There was no effect of condition on blood lactate, or saliva testosterone and cortisol responses (P>0.05). Neuromuscular electrical stimulation improves recovery from intensive training in professional team sports players. This strategy offers an easily applied recovery strategy which may have particular application during sleep and travel. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Survey of how different groups of veterinarians manage the use of neuromuscular blocking agents in anesthetized dogs.

PubMed

Martin-Flores, Manuel; Sakai, Daniel M; Campoy, Luis; Gleed, Robin D

2018-03-23

To analyze practice habits associated with the use, reversal and monitoring of nondepolarizing neuromuscular blocking agents (NMBAs) in dogs by different groups of veterinarians. Online anonymous survey to veterinarians. Data from 390 answered surveys. A questionnaire was sent to e-mail list servers of the American College of Veterinary Anesthesia and Analgesia (ACVAA-list), Sociedad Española de Anestesia y Analgesia Veterinaria (SEEAV-list), Colégio Brasileiro de Anestesiologia Veterinária (Brazilian College of Veterinary Anesthesiology; CBAV-list) and American College of Veterinary Ophthalmologists (ACVO-list) to elicit information regarding use of NMBAs and reversal agents, monitoring techniques, criteria for redosing, reversing and assessing adequacy of recovery of neuromuscular function. Binomial logistic regression was used to test for association between responses and group of veterinarians in selected questions. Veterinarians of the ACVO-list use NMBAs on a higher fraction of their caseload than other groups (all p < 0.0001). Subjective assessment (observation) of spontaneous movement, including spontaneous breathing, is the most common method for assessing neuromuscular function (43% of pooled responses); 18% of participants always reverse NMBAs, whereas 16% never reverse them. Restoration of neuromuscular function is assessed subjectively by 35% of respondents. Residual neuromuscular block is the most common concern regarding the use of NMBAs for all groups of veterinarians. Side effects of reversal agents (anticholinesterases) were of least concern for all groups. While most veterinarians are concerned about residual neuromuscular block, relatively few steps are implemented to reduce the risks of this complication, such as routine use of quantitative neuromuscular monitoring or routine reversal of NMBAs. These results suggest a limitation in transferring information among groups of veterinarians, or in implementing techniques suggested by scientific research. Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization

PubMed Central

Papkovskaia, Tatiana D.; Chau, Kai-Yin; Inesta-Vaquera, Francisco; Papkovsky, Dmitri B.; Healy, Daniel G.; Nishio, Koji; Staddon, James; Duchen, Michael R.; Hardy, John; Schapira, Anthony H.V.; Cooper, J. Mark

2012-01-01

The G2019S leucine rich repeat kinase 2 (LRRK2) mutation is the most common genetic cause of Parkinson's disease (PD), clinically and pathologically indistinguishable from idiopathic PD. Mitochondrial abnormalities are a common feature in PD pathogenesis and we have investigated the impact of G2019S mutant LRRK2 expression on mitochondrial bioenergetics. LRRK2 protein expression was detected in fibroblasts and lymphoblasts at levels higher than those observed in the mouse brain. The presence of G2019S LRRK2 mutation did not influence LRRK2 expression in fibroblasts. However, the expression of the G2019S LRRK2 mutation in both fibroblast and neuroblastoma cells was associated with mitochondrial uncoupling. This was characterized by decreased mitochondrial membrane potential and increased oxygen utilization under basal and oligomycin-inhibited conditions. This resulted in a decrease in cellular ATP levels consistent with compromised cellular function. This uncoupling of mitochondrial oxidative phosphorylation was associated with a cell-specific increase in uncoupling protein (UCP) 2 and 4 expression. Restoration of mitochondrial membrane potential by the UCP inhibitor genipin confirmed the role of UCPs in this mechanism. The G2019S LRRK2-induced mitochondrial uncoupling and UCP4 mRNA up-regulation were LRRK2 kinase-dependent, whereas endogenous LRRK2 levels were required for constitutive UCP expression. We propose that normal mitochondrial function was deregulated by the expression of G2019S LRRK2 in a kinase-dependent mechanism that is a modification of the normal LRRK2 function, and this leads to the vulnerability of selected neuronal populations in PD. PMID:22736029

Mild uncoupling of respiration and phosphorylation as a mechanism providing nephro- and neuroprotective effects of penetrating cations of the SkQ family.

PubMed

Plotnikov, E Y; Silachev, D N; Jankauskas, S S; Rokitskaya, T I; Chupyrkina, A A; Pevzner, I B; Zorova, L D; Isaev, N K; Antonenko, Y N; Skulachev, V P; Zorov, D B

2012-09-01

It is generally accepted that mitochondrial production of reactive oxygen species is nonlinearly related to the value of the mitochondrial membrane potential with significant increment at values exceeding 150 mV. Due to this, high values of the membrane potential are highly dangerous, specifically under pathological conditions associated with oxidative stress. Mild uncoupling of oxidative phosphorylation is an approach to preventing hyperpolarization of the mitochondrial membrane. We confirmed data obtained earlier in our group that dodecylrhodamine 19 (C(12)R1) (a penetrating cation from SkQ family not possessing a plastoquinone group) has uncoupling properties, this fact making it highly potent for use in prevention of pathologies associated with oxidative stress induced by mitochondrial hyperpolarization. Further experiments showed that C(12)R1 provided nephroprotection under ischemia/reperfusion of the kidney as well as under rhabdomyolysis through diminishing of renal dysfunction manifested by elevated level of blood creatinine and urea. Similar nephroprotective properties were observed for low doses (275 nmol/kg) of the conventional uncoupler 2,4-dinitrophenol. Another penetrating cation that did not demonstrate protonophorous activity (SkQR4) had no effect on renal dysfunction. In experiments with induced ischemic stroke, C(12)R1 did not have any effect on the area of ischemic damage, but it significantly lowered neurological deficit. We conclude that beneficial effects of penetrating cation derivatives of rhodamine 19 in renal pathologies and brain ischemia may be at least partially explained by uncoupling of oxidation and phosphorylation.

Availability of the key metabolic substrates dictates the respiratory response of cancer cells to the mitochondrial uncoupling.

PubMed

Zhdanov, Alexander V; Waters, Alicia H C; Golubeva, Anna V; Dmitriev, Ruslan I; Papkovsky, Dmitri B

2014-01-01

Active glycolysis and glutaminolysis provide bioenergetic stability of cancer cells in physiological conditions. Under hypoxia, metabolic and mitochondrial disorders, or pharmacological treatment, a deficit of key metabolic substrates may become life-threatening to cancer cells. We analysed the effects of mitochondrial uncoupling by FCCP on the respiration of cells fed by different combinations of Glc, Gal, Gln and Pyr. In cancer PC12 and HCT116 cells, a large increase in O2 consumption rate (OCR) upon uncoupling was only seen when Gln was combined with either Glc or Pyr. Inhibition of glutaminolysis with BPTES abolished this effect. Despite the key role of Gln, addition of FCCP inhibited respiration and induced apoptosis in cells supplied with Gln alone or Gal/Gln. For all substrate combinations, amplitude of respiratory responses to FCCP did not correlate with Akt, Erk and AMPK phosphorylation, cellular ATP, and resting OCR, mitochondrial Ca(2+) or membrane potential. However, we propose that proton motive force could modulate respiratory response to FCCP by regulating mitochondrial transport of Gln and Pyr, which decreases upon mitochondrial depolarisation. As a result, an increase in respiration upon uncoupling is abolished in cells, deprived of Gln or Pyr (Glc). Unlike PC12 or HCT116 cells, mouse embryonic fibroblasts were capable of generating pronounced response to FCCP when deprived of Gln, thus exhibiting lower dependence on glutaminolysis. Overall, the differential regulation of the respiratory response to FCCP by metabolic environment suggests that mitochondrial uncoupling has a potential for substrate-specific inhibition of cell function, and can be explored for selective cancer treatment. © 2013.

The development of structure-activity relationships for mitochondrial dysfunction: uncoupling of oxidative phosphorylation.

PubMed

Naven, Russell T; Swiss, Rachel; Klug-McLeod, Jacquelyn; Will, Yvonne; Greene, Nigel

2013-01-01

Mitochondrial dysfunction has been implicated as an important factor in the development of idiosyncratic organ toxicity. An ability to predict mitochondrial dysfunction early in the drug development process enables the deselection of those drug candidates with potential safety liabilities, allowing resources to be focused on those compounds with the highest chance of success to the market. A database of greater than 2000 compounds was analyzed to identify structural and physicochemical features associated with the uncoupling of oxidative phosphorylation (herein defined as an increase in basal respiration). Many toxicophores associated with potent uncoupling activity were identified, and these could be divided into two main mechanistic classes, protonophores and redox cyclers. For the protonophores, potent uncoupling activity was often promoted by high lipophilicity and apparent stabilization of the anionic charge resulting from deprotonation of the protonophore. The potency of redox cyclers did not appear to be prone to variations in lipophilicity. Only 11 toxicophores were of sufficient predictive performance that they could be incorporated into a structural-alert model. Each alert was associated with one of three confidence levels (high, medium, and low) depending upon the lipophilicity-activity profile of the structural class. The final model identified over 68% of those compounds with potent uncoupling activity and with a value for specificity above 99%. We discuss the advantages and limitations of this approach and conclude that although structural alert methodology is useful for identifying toxicophores associated with mitochondrial dysfunction, they are not a replacement for the mitochondrial dysfunction assays in early screening paradigms.

Intrinsic uncoupling of mitochondrial proton pumps. 2. Modeling studies.

PubMed

Pietrobon, D; Zoratti, M; Azzone, G F; Caplan, S R

1986-02-25

The thermodynamic and kinetic properties associated with intrinsic uncoupling in a six-state model of a redox proton pump have been studied by computing the flow-force relations for different degrees of coupling. Analysis of these relations shows the regulatory influence of the thermodynamic forces on the extent and relative contributions of redox slip and proton slip. Inhibition has been introduced into the model in two different ways, corresponding to possible modes of action of experimental inhibitors. Experiments relating the rate of electron transfer to delta microH at static head upon progressive inhibition of the pumps have been simulated considering (1) the limiting case that the nonzero rate of electron transfer at static head is only due to intrinsic uncoupling (no leaks) and (2) the experimentally observed case that about 30% of the nonzero rate of electron transfer at static head is due to a constant proton leakage conductance in parallel with the pumps, the rest being due to intrinsic uncoupling. The same simulations have been performed for experiments in which the rate of electron transfer is varied by varying the substrate concentration rather than by using an inhibitor. The corresponding experimental results obtained by measuring delta microH and the rate of electron transfer at different succinate concentrations in rat liver mitochondria are presented. Comparison between simulated behavior and experimental results leads to the general conclusion that the typical relationship between rate of electron transfer and delta microH found in mitochondria at static head could certainly be a manifestation of some degree of intrinsic uncoupling in the redox proton pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondrial Proton Leak Plays a Critical Role in Pathogenesis of Cardiovascular Diseases.

PubMed

Cheng, Jiali; Nanayakkara, Gayani; Shao, Ying; Cueto, Ramon; Wang, Luqiao; Yang, William Y; Tian, Ye; Wang, Hong; Yang, Xiaofeng

2017-01-01

Mitochondrial proton leak is the principal mechanism that incompletely couples substrate oxygen to ATP generation. This chapter briefly addresses the recent progress made in understanding the role of proton leak in the pathogenesis of cardiovascular diseases. Majority of the proton conductance is mediated by uncoupling proteins (UCPs) located in the mitochondrial inner membrane. It is evident that the proton leak and reactive oxygen species (ROS) generated from electron transport chain (ETC) in mitochondria are linked to each other. Increased ROS production has been shown to induce proton conductance, and in return, increased proton conductance suppresses ROS production, suggesting the existence of a positive feedback loop that protects the biological systems from detrimental effects of augmented oxidative stress. There is mounting evidence attributing to proton leak and uncoupling proteins a crucial role in the pathogenesis of cardiovascular disease. We can surmise the role of "uncoupling" in cardiovascular disorders as follows; First, the magnitude of the proton leak and the mechanism involved in mediating the proton leak determine whether there is a protective effect against ischemia-reperfusion (IR) injury. Second, uncoupling by UCP2 preserves vascular function in diet-induced obese mice as well as in diabetes. Third, etiology determines whether the proton conductance is altered or not during hypertension. And fourth, proton leak regulates ATP synthesis-uncoupled mitochondrial ROS generation, which determines pathological activation of endothelial cells for recruitment of inflammatory cells. Continue effort in improving our understanding in the role of proton leak in the pathogenesis of cardiovascular and metabolic diseases would lead to identification of novel therapeutic targets for treatment.

The plant energy-dissipating mitochondrial systems: depicting the genomic structure and the expression profiles of the gene families of uncoupling protein and alternative oxidase in monocots and dicots.

PubMed

Borecky, Jirí; Nogueira, Fábio T S; de Oliveira, Kívia A P; Maia, Ivan G; Vercesi, Aníbal E; Arruda, Paulo

2006-01-01

The simultaneous existence of alternative oxidases and uncoupling proteins in plants has raised the question as to why plants need two energy-dissipating systems with apparently similar physiological functions. A probably complete plant uncoupling protein gene family is described and the expression profiles of this family compared with the multigene family of alternative oxidases in Arabidopsis thaliana and sugarcane (Saccharum sp.) employed as dicot and monocot models, respectively. In total, six uncoupling protein genes, AtPUMP1-6, were recognized within the Arabidopsis genome and five (SsPUMP1-5) in a sugarcane EST database. The recombinant AtPUMP5 protein displayed similar biochemical properties as AtPUMP1. Sugarcane possessed four Arabidopsis AOx1-type orthologues (SsAOx1a-1d); no sugarcane orthologue corresponding to Arabidopsis AOx2-type genes was identified. Phylogenetic and expression analyses suggested that AtAOx1d does not belong to the AOx1-type family but forms a new (AOx3-type) family. Tissue-enriched expression profiling revealed that uncoupling protein genes were expressed more ubiquitously than the alternative oxidase genes. Distinct expression patterns among gene family members were observed between monocots and dicots and during chilling stress. These findings suggest that the members of each energy-dissipating system are subject to different cell or tissue/organ transcriptional regulation. As a result, plants may respond more flexibly to adverse biotic and abiotic conditions, in which oxidative stress is involved.

Whole genome siRNA cell-based screen links mitochondria to Akt signaling network through uncoupling of electron transport chain

PubMed Central

Senapedis, William T.; Kennedy, Caleb J.; Boyle, Patrick M.; Silver, Pamela A.

2011-01-01

Forkhead transcription factors (FOXOs) alter a diverse array of cellular processes including the cell cycle, oxidative stress resistance, and aging. Insulin/Akt activation directs phosphorylation and cytoplasmic sequestration of FOXO away from its target genes and serves as an endpoint of a complex signaling network. Using a human genome small interfering RNA (siRNA) library in a cell-based assay, we identified an extensive network of proteins involved in nuclear export, focal adhesion, and mitochondrial respiration not previously implicated in FOXO localization. Furthermore, a detailed examination of mitochondrial factors revealed that loss of uncoupling protein 5 (UCP5) modifies the energy balance and increases free radicals through up-regulation of uncoupling protein 3 (UCP3). The increased superoxide content induces c-Jun N-terminal kinase 1 (JNK1) kinase activity, which in turn affects FOXO localization through a compensatory dephosphorylation of Akt. The resulting nuclear FOXO increases expression of target genes, including mitochondrial superoxide dismutase. By connecting free radical defense and mitochondrial uncoupling to Akt/FOXO signaling, these results have implications in obesity and type 2 diabetes development and the potential for therapeutic intervention. PMID:21460183

Whole genome siRNA cell-based screen links mitochondria to Akt signaling network through uncoupling of electron transport chain.

PubMed

Senapedis, William T; Kennedy, Caleb J; Boyle, Patrick M; Silver, Pamela A

2011-05-15

Forkhead transcription factors (FOXOs) alter a diverse array of cellular processes including the cell cycle, oxidative stress resistance, and aging. Insulin/Akt activation directs phosphorylation and cytoplasmic sequestration of FOXO away from its target genes and serves as an endpoint of a complex signaling network. Using a human genome small interfering RNA (siRNA) library in a cell-based assay, we identified an extensive network of proteins involved in nuclear export, focal adhesion, and mitochondrial respiration not previously implicated in FOXO localization. Furthermore, a detailed examination of mitochondrial factors revealed that loss of uncoupling protein 5 (UCP5) modifies the energy balance and increases free radicals through up-regulation of uncoupling protein 3 (UCP3). The increased superoxide content induces c-Jun N-terminal kinase 1 (JNK1) kinase activity, which in turn affects FOXO localization through a compensatory dephosphorylation of Akt. The resulting nuclear FOXO increases expression of target genes, including mitochondrial superoxide dismutase. By connecting free radical defense and mitochondrial uncoupling to Akt/FOXO signaling, these results have implications in obesity and type 2 diabetes development and the potential for therapeutic intervention.

Kidney transplantation restored uncoupled bone turnover in end-stage renal disease.

PubMed

Kawarazaki, Hiroo; Shibagaki, Yugo; Kido, Ryo; Nakajima, Ichiro; Fuchinoue, Shohei; Ando, Katsuyuki; Fujita, Toshiro; Fukagawa, Masafumi; Teraoka, Satoshi; Fukumoto, Seiji

2012-07-01

While kidney transplantation (KTx) reverses many disorders associated with end-stage renal disease (ESRD), patients who have received KTx often have chronic kidney disease and bone and mineral disorder (CKD-MBD). However, it is unknown how bone metabolism changes by KTx. Living donor-KTx recipients (n = 34) at Tokyo Women's Medical University were prospectively recruited and the levels of bone-specific alkaline phosphatase (BAP) and serum cross-linked N-telopeptides of Type 1 collagen (NTX) were measured before, 6 and 12 months after transplantation. Before KTx, serum BAP was within the reference range in more than half of patients while NTX was high in most patients. Serum NTX was higher in patients with longer dialysis durations compared to that with shorter durations before KTx. However, there was no difference in serum BAP between these patients. After KTx, BAP increased while NTX decreased along with the decline of PTH. In addition, the numbers of patients who showed high BAP and NTX were comparable after KTx. These results suggest that bone formation is suppressed and uncoupled with bone resorption in patients with ESRD and this uncoupling is restored by KTx. Further studies are necessary to clarify the mechanism of bone uncoupling in patients with ESRD.

Nitric oxide, PKC-ε, and connexin43 are crucial for ischemic preconditioning-induced chemical gap junction uncoupling

PubMed Central

Sun, Tao; Hao, Li; Lin, Ming-Jie; Zhong, Jing-Quan

2016-01-01

Ischemic preconditioning (IPC) maintains connexin43 (Cx43) phosphorylation and reduces chemical gap junction (GJ) coupling in cardiomyocytes to protect against ischemic damage. However, the signal transduction pathways underlying these effects are not fully understood. Here, we investigated whether nitric oxide (NO) and protein kinase C-ε (PKC-ε) contribute to IPC-induced cardioprotection by maintaining Cx43 phosphorylation and inhibiting chemical GJ coupling. IPC reduced ischemia-induced myocardial infarction and increased cardiomyocyte survival; phosphorylated Cx43, eNOS, and PKC-ε levels; and chemical GJ uncoupling. Administration of the NO donor SNAP mimicked the effects of IPC both in vivo and in vitro, maintaining Cx43 phosphorylation, promoting chemical GJ uncoupling, and reducing myocardial infarction. Preincubation with the NO synthase inhibitor L-NAME or PKC-ε translocation inhibitory peptide (PKC-ε-TIP) abolished these effects of IPC. Additionally, by inducing NO production, IPC induced translocation of PKC-ε, but not PKC-δ, from the cytosolic to the membrane fraction in primary cardiac myocytes. IPC-induced cardioprotection thus involves increased NO production, PKC-ε translocation, Cx43 phosphorylation, and chemical GJ uncoupling. PMID:27655723

Uncoupling RARA transcriptional activation and degradation clarifies the bases for APL response to therapies

PubMed Central

Ablain, Julien; Leiva, Magdalena; Peres, Laurent; Fonsart, Julien; Anthony, Elodie

2013-01-01

In PML/RARA-driven acute promyelocytic leukemia (APL), retinoic acid (RA) induces leukemia cell differentiation and transiently clears the disease. Molecularly, RA activates PML/RARA-dependent transcription and also initiates its proteasome-mediated degradation. In contrast, arsenic, the other potent anti-APL therapy, only induces PML/RARA degradation by specifically targeting its PML moiety. The respective contributions of RA-triggered transcriptional activation and proteolysis to clinical response remain disputed. Here, we identify synthetic retinoids that potently activate RARA- or PML/RARA-dependent transcription, but fail to down-regulate RARA or PML/RARA protein levels. Similar to RA, these uncoupled retinoids elicit terminal differentiation, but unexpectedly fail to impair leukemia-initiating activity of PML/RARA-transformed cells ex vivo or in vivo. Accordingly, the survival benefit conferred by uncoupled retinoids in APL mice is dramatically lower than the one provided by RA. Differentiated APL blasts sorted from uncoupled retinoid–treated mice retain PML/RARA expression and reinitiate APL in secondary transplants. Thus, differentiation is insufficient for APL eradication, whereas PML/RARA loss is essential. These observations unify the modes of action of RA and arsenic and shed light on the potency of their combination in mice or patients. PMID:23509325

Uncoupling RARA transcriptional activation and degradation clarifies the bases for APL response to therapies.

PubMed

Ablain, Julien; Leiva, Magdalena; Peres, Laurent; Fonsart, Julien; Anthony, Elodie; de Thé, Hugues

2013-04-08

In PML/RARA-driven acute promyelocytic leukemia (APL), retinoic acid (RA) induces leukemia cell differentiation and transiently clears the disease. Molecularly, RA activates PML/RARA-dependent transcription and also initiates its proteasome-mediated degradation. In contrast, arsenic, the other potent anti-APL therapy, only induces PML/RARA degradation by specifically targeting its PML moiety. The respective contributions of RA-triggered transcriptional activation and proteolysis to clinical response remain disputed. Here, we identify synthetic retinoids that potently activate RARA- or PML/RARA-dependent transcription, but fail to down-regulate RARA or PML/RARA protein levels. Similar to RA, these uncoupled retinoids elicit terminal differentiation, but unexpectedly fail to impair leukemia-initiating activity of PML/RARA-transformed cells ex vivo or in vivo. Accordingly, the survival benefit conferred by uncoupled retinoids in APL mice is dramatically lower than the one provided by RA. Differentiated APL blasts sorted from uncoupled retinoid-treated mice retain PML/RARA expression and reinitiate APL in secondary transplants. Thus, differentiation is insufficient for APL eradication, whereas PML/RARA loss is essential. These observations unify the modes of action of RA and arsenic and shed light on the potency of their combination in mice or patients.

Influence of antimycin A and uncouplers on anaerobic photosynthesis in isolated chloroplasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slovacek, R.E.; Hind, G.

1977-10-01

Anaerobiosis depresses the light- and bicarbonate-saturated rates of O/sub 2/ evolution in intact spinach (Spinacia oleracea) chloroplasts by as much as 3-fold from those observed under aerobic conditions. These lower rates are accelerated 2-fold or more by the addition of 1 ..mu..m antimycin A or by low concentrations of the uncouplers 0.3 mM NH/sub 4/Cl or 0.25 ..mu..m carbonyl cyanide m-chlorophenylhydrazone. Oxaloacetate and glycerate 3-phosphate reduction rates are also increased by antimycin A or an uncoupler under anaerobic conditions. At intermediate light intensities, the rate accelerations by either antimycin A or uncoupler are inversely proportional to the adenosine 5'-triphosphate demandmore » of the reduction process for the acceptors HCO/sub 3//sup -/, glycerate 3-phosphate, and oxaloacetate. The acceleration of bicarbonate-supported O/sub 2/ evolution may also be produced by adding an adenosine 5'-triphosphate sink (ribose 5-phosphate) to anaerobic chloroplasts. The above results suggest that a proton gradient back pressure resulting from antimycin A-sensitive cyclic electron flow is responsible for the depression of light-saturated photosynthesis under anaerobiosis.« less

Neuromuscular control and rehabilitation of the unstable ankle

PubMed Central

Hung, You-jou

2015-01-01

Lateral ankle sprain is a common orthopedic injury with a very high recurrence rate in athletes. After decades of research, it is still unclear what contributes to the high recurrence rate of ankle sprain, and what is the most effective intervention to reduce the incident of initial and recurrent injuries. In addition, clinicians often implement balance training as part of the rehabilitation protocol in hopes of enhancing the neuromuscular control and proprioception of the ankle joint. However, there is no consensus on whether the neuromuscular control and proprioception are compromised in unstable ankles. To reduce the prevalence of ankle sprains, the effectiveness of engaging balance training to enhance the neuromuscular control and proprioception of the ankle joint is also questionable. PMID:26085985

The use of pesticides in Belgian illicit indoor cannabis plantations.

PubMed

Cuypers, Eva; Vanhove, Wouter; Gotink, Joachim; Bonneure, Arne; Van Damme, Patrick; Tytgat, Jan

2017-08-01

Cannabis (Cannabis spp.) use and cultivation continue to increase in many (European) countries. The illicit indoor cannabis plantations that supply Belgian and European cannabis markets create problems and concerns about health and safety of intervention staff, dismantling companies, the direct environment of cannabis plantations and, eventually, of cannabis users. Main risks may come from pesticide residues on plants, cultivation infrastructure and materials; left-over plant growth-promoting substances; mycotoxins from fungal pathogens on harvested plants; and/or high levels of cannabinoids in cannabis plant parts for consumption. In the present research, we report on pesticides found in illicit indoor cannabis plantations in Belgium. EN15662 QuEChERS extraction method and LC-MS/MS analysis were used to identify pesticides in indoor cannabis plantations and thus to evaluate the hazards associated with the use, cultivation and removal of cannabis plants in plantations as well as with dismantling activities in the cultivation rooms. We found pesticides in 64.3% of 72 cannabis plant samples and in 65.2% of 46 carbon filter cloth samples. Overall, 19 pesticides belonging to different chemical classes were identified. We found o-phenylphenol, bifenazate, cypermethrin, imidacloprid, propamocarb, propiconazole and tebuconazole, which is consistent with the commonly reported pesticides from literature. In only a few cases, pesticides found in bottles with a commercial label, were also identified in plant or stagnant water samples collected from the growth rooms where the bottles had been collected. We further revealed that, even though most pesticides have a low volatility, they could be detected from the carbon filters hanging at the ceiling of cultivation rooms. As a result, it is likely that pesticides also prevail in the plantation atmosphere during and after cultivation. The risk of inhaling the latter pesticides increases when plants sprayed with pesticides are intensively manipulated during dismantling activities. We conclude that pesticides represent an underestimated and under-documented health risk for intervention staff. The standard procedure for dismantling illicit indoor cannabis cultivation sites should be improved by including guidelines for appropriate personal protection equipment and dismantling protocols that take into account all possible hazards. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation, hematology and kidney injury markers in residents of an e-waste dismantling area in Zhejiang, China.

PubMed

Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Wang, Xiaofeng

2015-12-01

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two typical categories of contaminants released from e-waste dismantling environments. In China, the body burdens of PCBs and PBDEs are associated with abnormal thyroid hormones in populations from e-waste dismantling sites, but the results are limited and contradictory. In this study, we measured the serum levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an e-waste dismantling area and in 15 residents in a control area. Additionally, we also measured some lymphocyte proliferation indexes, hematologic parameters and kidney injury markers, including white blood cells, neutrophils, monocytes, lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin (β2-MG). The results indicated that the mean level of ΣPCBs in the exposure group was significantly higher than that in the control group (964.39 and 67.98 ng g(-1), p<0.0001), but the mean level of ΣPBDEs in the exposure group was not significantly higher than that in the controls (139.32 vs. 75.74 ng g(-1), p>0.05). We determined that serum levels of FT3, FT4, monocytes and lymphocytes were significantly lower, whereas the levels of neutrophils, hemoglobin, platelets and serum creatinine were significantly higher in the exposed group (p<0.05). The mean level of ΣPCBs was negatively correlated with levels of FT3, FT4, monocytes and lymphocytes (p<0.05) and positively correlated with levels of neutrophils, hemoglobin, serum creatinine and β2-MG (p<0.05). Additionally, the mean level of ΣPBDEs was positively correlated with levels of white blood cells, hemoglobin and platelets (p<0.05). Our data suggest that exposure to an e-waste dismantling environment may increase the body burdens of PCBs and the specific PBDEs congeners in native residents and that the contaminants released from e-waste may contribute to abnormal changes in body levels of thyroid hormone, hematology and kidney injury markers. Copyright © 2015. Published by Elsevier B.V.

Effect of E-waste Recycling on Urinary Metabolites of Organophosphate Flame Retardants and Plasticizers and Their Association with Oxidative Stress.

PubMed

Lu, Shao-You; Li, Yan-Xi; Zhang, Tao; Cai, Dan; Ruan, Ju-Jun; Huang, Ming-Zhi; Wang, Lei; Zhang, Jian-Qing; Qiu, Rong-Liang

2017-02-21

In this study, three chlorinated (Cl-mOPs) and five nonchlorinated (NCl-mOPs) organophosphate metabolites were determined in urine samples collected from participants living in an electronic waste (e-waste) dismantling area (n = 175) and two reference areas (rural, n = 29 and urban, n = 17) in southern China. Bis(2-chloroethyl) phosphate [BCEP, geometric mean (GM): 0.72 ng/mL] was the most abundant Cl-mOP, and diphenyl phosphate (DPHP, 0.55 ng/mL) was the most abundant NCl-mOP. The GM concentrations of mOPs in the e-waste dismantling sites were higher than those in the rural control site. These differences were significant for BCEP (p < 0.05) and DPHP (p < 0.01). Results suggested that e-waste dismantling activities contributed to human exposure to OPs. In the e-waste sites, the urinary concentrations of bis(2-chloro-isopropyl) phosphate (r = 0.484, p < 0.01), BCEP (r = 0.504, p < 0.01), dibutyl phosphate (r = 0.214, p < 0.05), and DPHP (r = 0.440, p < 0.01) were significantly increased as the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative stress, increased. Our results also suggested that human exposure to OPs might be correlated with DNA oxidative stress for residents in e-waste dismantling areas. To our knowledge, this study is the first to report the urinary levels of mOPs in China and examine the association between OP exposure and 8-OHdG in humans.

An anterior cruciate ligament injury does not affect the neuromuscular function of the non-injured leg except for dynamic balance and voluntary quadriceps activation.

PubMed

Zult, Tjerk; Gokeler, Alli; van Raay, Jos J A M; Brouwer, Reinoud W; Zijdewind, Inge; Hortobágyi, Tibor

2017-01-01

The function of the anterior cruciate ligament (ACL) patients' non-injured leg is relevant in light of the high incidence of secondary ACL injuries on the contralateral side. However, the non-injured leg's function has only been examined for a selected number of neuromuscular outcomes and often without appropriate control groups. We measured a broad array of neuromuscular functions between legs of ACL patients and compared outcomes to age, sex, and physical activity matched controls. Thirty-two ACL-deficient patients (208 ± 145 days post-injury) and active and less-active controls (N = 20 each) participated in the study. We measured single- and multi-joint neuromuscular function in both legs in each group and expressed the overall neuromuscular function in each leg by calculating a mean z-score across all neuromuscular measures. A group by leg MANOVA and ANOVA were performed to examine group and leg differences for the selected outcomes. After an ACL injury, duration (-4.3 h/week) and level (Tegner activity score of -3.9) of sports activity decreased and was comparable to less-active controls. ACL patients showed bilateral impairments in the star excursion balance test compared to both control groups (P ≤ 0.004) and for central activation ratio compared to active controls (P ≤ 0.002). There were between-leg differences within each group for maximal quadriceps and hamstring strength, voluntary quadriceps activation, star excursion balance test performance, and single-leg hop distance (all P < 0.05), but there were no significant differences in quadriceps force accuracy and variability, knee joint proprioception, and static balance. Overall neuromuscular function (mean z-score) did not differ between groups, but ACL patients' non-injured leg displayed better neuromuscular function than the injured leg (P < 0.05). Except for poorer dynamic balance and reduced quadriceps activation, ACL patients had no bilateral neuromuscular deficits despite reductions in physical activity after injury. Therapists can use the non-injured leg as a reference to assess the injured leg's function for tasks measured in the present study, excluding dynamic balance and quadriceps activation. Rehabilitation after an ACL injury should be mainly focused on the injured leg. III.

Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report

PubMed Central

2011-01-01

Background Ankle joint sprain and the subsequent development of chronic ankle instability (CAI) are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI. Methods The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed/agility drills. The outcome measures chosen to assess for interventional efficacy were: [1] Cumberland Ankle Instability Tool (CAIT) scores, [2] Star Excursion Balance Test (SEBT) reach distances, [3] ankle joint plantar flexion during drop landing and drop vertical jumping, and [4] ground reaction forces (GRFs) during walking. Results CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention. Conclusions The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors. PMID:21658224

A comparison between the blocking actions of 2-(4-phenylpiperidino) cyclohexanol (AH 5183) and its N-methyl quaternary analogue (AH 5954)

PubMed Central

Marshall, I. G.

1970-01-01

1. The neuromuscular blocking activities of AH 5183 (2-(4-phenylpiperidino) cyclohexanol) and its N-methyl quaternary analogue (AH 5954) were compared in rapidly stimulated nerve-skeletal muscle preparations of the rat, chicken and cat. 2. The evidence indicated that in isolated preparations the neuromuscular block produced by both AH 5183 and AH 5954 was primarily pre-junctional in origin. That produced by AH 5954 was readily reversible either by washing the tissue or by reducing the stimulation frequency, whereas that produced by AH 5183 was difficult to reverse in these ways. 3. Low doses of AH 5954 sensitized the rat hemidiaphragm preparation to the neuromuscular blocking action of choline. The neuromuscular block produced by choline was reversible by tetraethylammonium but not by neostigmine. This suggested that the blocking action of choline is at least partly pre-junctional in nature. 4. In anaesthetized cats AH 5954 possessed a biphasic neuromuscular blocking action. The initial phase was rapid in onset, suggestive of a post-junctional action, whereas the second phase was prolonged and reversible by choline, suggestive of a prejunctional inhibitory action on the choline transport mechanism. AH 5183 produced no initial blocking action and was irreversible by choline. 5. Both AH 5183 and AH 5954 possessed local anaesthetic and α-adrenoceptor blocking actions. These actions and the neuromuscular blocking action were affected to different degrees by quaternization, suggesting that the three main actions of the two drugs are independent. 6. It was concluded that AH 5954 and AH 5183 act at different pre-junctional sites at the neuromuscular junction, AH 5954 acting extraneuronally by inhibiting choline transport and AH 5183 intraneuronally at the level of the synaptic vesicle membrane. PMID:4395087

Neuromuscular control and ankle instability.

PubMed

Gutierrez, Gregory M; Kaminski, Thomas W; Douex, Al T

2009-04-01

Lateral ankle sprains (LAS) are common injuries in athletics and daily activity. Although most are resolved with conservative treatment, others develop chronic ankle instability (AI)-a condition associated with persistent pain, weakness, and instability-both mechanical (such as ligamentous laxity) and functional (neuromuscular impairment with or without mechanical laxity). The predominant theory in AI is one of articular deafferentation from the injury, affecting closed-loop (feedback/reflexive) neuromuscular control, but recent research has called that theory into question. A considerable amount of attention has been directed toward understanding the underlying causes of this pathology; however, little is known concerning the neuromuscular mechanisms behind the development of AI. The purpose of this review is to summarize the available literature on neuromuscular control in uninjured individuals and individuals with AI. Based on available research and reasonable speculation, it seems that open-loop (feedforward/anticipatory) neuromuscular control may be more important for the maintenance of dynamic joint stability than closed-loop control systems that rely primarily on proprioception. Therefore, incorporating perturbation activities into patient rehabilitation schemes may be of some benefit in enhancing these open-loop control mechanisms. Despite the amount of research conducted in this area, analysis of individuals with AI during dynamic conditions is limited. Future work should aim to evaluate dynamic perturbations in individuals with AI, as well as subjects who have a history of at least one LAS and never experienced recurrent symptoms. These potential findings may help elucidate some compensatory mechanisms, or more appropriate neuromuscular control strategies after an LAS event, thus laying the groundwork for future intervention studies that can attempt to reduce the incidence and severity of acute and chronic lateral ankle injury.

Full-movement neuromuscular electrical stimulation improves plantar flexor spasticity and ankle active dorsiflexion in stroke patients: a randomized controlled study.

PubMed

Wang, Yong-Hui; Meng, Fei; Zhang, Yang; Xu, Mao-Yu; Yue, Shou-Wei

2016-06-01

To investigate whether full-movement neuromuscular electrical stimulation, which can generate full range of movement, reduces spasticity and/or improves motor function more effectively than control, sensory threshold-neuromuscular electrical stimulation, and motor threshold-neuromuscular electrical stimulation in sub-acute stroke patients. A randomized, single-blind, controlled study. Physical therapy room and functional assessment room. A total of 72 adult patients with sub-acute post-stroke hemiplegia and plantar flexor spasticity. Patients received 30-minute sessions of neuromuscular electrical stimulation on the motor points of the extensor hallucis and digitorum longus twice a day, five days per week for four weeks. Composite Spasticity Scale, Ankle Active Dorsiflexion Score, and walking time in the Timed Up and Go Test were assessed at pretreatment, posttreatment, and at two-week follow-up. After four weeks of treatment, when comparing interclass pretreatment and posttreatment, only the full-movement neuromuscular electrical stimulation group had a significant reduction in the Composite Spasticity Scale (mean % reduction = 19.91(4.96)%, F = 3.878, p < 0.05) and improvement in the Ankle Active Dorsiflexion Score (mean scores = 3.29(0.91), F = 3.140, p < 0.05). Furthermore, these improvements were maintained two weeks after the treatment ended. However, there were no significant differences in the walking time after four weeks of treatment among the four groups (F = 1.861, p > 0.05). Full-movement neuromuscular electrical stimulation with a stimulus intensity capable of generating full movement can significantly reduce plantar flexor spasticity and improve ankle active dorsiflexion, but cannot decrease walking time in the Timed Up and Go Test in sub-acute stroke patients. © The Author(s) 2015.

Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report.

PubMed

O'Driscoll, Jeremiah; Kerin, Fearghal; Delahunt, Eamonn

2011-06-09

Ankle joint sprain and the subsequent development of chronic ankle instability (CAI) are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI. The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed/agility drills. The outcome measures chosen to assess for interventional efficacy were: 1 Cumberland Ankle Instability Tool (CAIT) scores, 2 Star Excursion Balance Test (SEBT) reach distances, 3 ankle joint plantar flexion during drop landing and drop vertical jumping, and 4 ground reaction forces (GRFs) during walking. CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention. The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors.

A systematic review and meta-analysis of lower limb neuromuscular alterations associated with knee osteoarthritis during level walking.

PubMed

Mills, Kathryn; Hunt, Michael A; Leigh, Ryan; Ferber, Reed

2013-08-01

Neuromuscular alterations are increasingly reported in individuals with knee osteoarthritis (KOA) during level walking. We aimed to determine which neuromuscular alterations are consistent in KOA individuals and how these may be influenced by osteoarthritis severity, varus alignment and/or joint laxity. Electronic databases were searched up to July 2012. Cross-sectional observational studies comparing lower-limb neuromuscular activity in individuals with KOA, healthy controls or with different KOA cohorts were included. Two reviewers assessed methodological quality. Effect sizes were used to quantify the magnitude of observed differences. Where studies were homogenous, effect sizes were pooled using a fixed-effects model. Fourteen studies examining neuromuscular alterations in indices of co-contraction, muscle amplitude and muscle activity duration were included. Data pooling revealed that moderate KOA individuals exhibit increased co-contraction of lateral knee muscles (ES 0.64 [0.3 to 0.97]) and moderately increased rectus femoris (ES 0.73 [0.23 to 1.22]), vastus lateralis (ES 0.77 [0.27 to 1.27]) and biceps femoris (ES 1.18 [0.67 to 1.7]) mean amplitude. Non-pooled data indicated prolonged activity of these muscles. Increased medial knee neuromuscular activity was prevalent for those exhibiting varus alignment and medial knee joint laxity. Interpretation Individuals with KOA exhibited increased co-contraction, amplitude and duration of lateral knee muscles regardless of disease severity, limb alignment or medial joint laxity. Individuals with severe disease, varus alignment and medial joint laxity demonstrate up-regulation of medial knee muscles. Future research investigating the efficacy of neuromuscular rehabilitation programs should consider the effect of simultaneous up-regulation of medial and lateral knee muscles on disease progression. © 2013.

Facilitatory effects of piracetam on excitability of motor nerve terminals and neuromuscular transmission.

PubMed

Hall, E D; Von Voigtlander, P F

1987-11-01

The possible in vivo facilitatory effects of the pyrrolidine acetamide no-otropic agent piracetam on neuromuscular transmission, were studied based upon reports of enhancement of central cholinergic function. Piracetam was shown to antagonize the lethal effects of the neuromuscular blocking agent hemicholinium-3 (HC-3), in female CF-1 mice when administered in a dose of 100 mg/kg (i.p.) simultaneously with HC-3. A 30 mg/kg (i.p.) dose of piracetam was ineffective by itself, although it potentiated the protective effects of choline (25 mg/kg i.p.). The analogs of piracetam, aniracetam, oxiracetam, pramiracetam and dupracetam also significantly antagonized the lethality of HC-3 at doses over a 30-300 mg/kg range. The acute facilitatory properties of piracetam on neuromuscular transmission were examined in more detail in vivo in the soleus nerve muscle preparation of the cat. A 100 mg/kg (i.v.) dose of piracetam, while having no effect on its own, significantly enhanced the ability of a 200 micrograms/kg (i.v.) dose of edrophonium to produce a potentiation of muscle contraction dependent on repetitive discharges in the soleus motor nerve terminals. In preparations in which the motor nerve terminals of the soleus were in a partially degenerated state as a result of section of the motor axons 48 hr earlier, piracetam acted to restore their sensitivity to edrophonium. Furthermore, in both normal and partially degenerated preparations, piracetam significantly decreased the neuromuscular blocking effects of a 150 micrograms/kg (i.v.) dose of d-tubocurarine. The mechanism of the neuromuscular facilitatory effects of piracetam on neuromuscular transmission is discussed in terms of an enhanced excitability of motor nerve terminals together with an action to increase the synthesis and/or release of acetylcholine.

Reversal of profound and "deep" residual rocuronium-induced neuromuscular blockade by sugammadex: a neurophysiological study.

PubMed

Pavoni, V; Gianesello, L; De Scisciolo, G; Provvedi, E; Horton, D; Barbagli, R; Conti, P; Conti, R; Giunta, F

2012-05-01

Sugammadex is the first of a new class of selective relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade (NMB) induced by the aminosteroid neuromuscular blocking drugs rocuronium and vecuronium. Neuromuscular blocking drugs block the transmission from the peripheral nerve to the muscle units, with reduction and disappearance of the evoked electromyographic activity. Usually, neuromuscular monitoring for the investigational reversal drug is performed by calibrated acceleromyography. The efficacy of sugammadex in reversing profound and "deep" residual rocuronium-induced NMB using myogenic motor evoked potentials (mMEPs) monitoring was evaluated. In this prospective trial, 30 consenting patients undergoing propofol-remifentanil anesthesia for spine surgery were enrolled and divided into two groups: Group 1, reversal of profound NMB (sugammadex 16 mg/Kg, 3 minutes after rocuronium 1.2 mg/Kg) and Group 2, reversal of "deep" residual NMB (sugammadex 4 mg/Kg, 15 minutes after rocuronium 0.6 mg/Kg). Myogenic MEPs registrations of upper and lower limbs and the diaphragm were performed, as well as TOF monitoring. After injection of 4 mg/Kg of sugammadex, the means of recovery time of the basal mMEPs amplitudes (diaphragm, and lower limbs and upper limbs) were 124±9.6, 143±163, 151±207 sec, respectively whereas after 16 mg/Kg of sugammadex the times were 109±13.8, 124±0.6, and 135±14.1 sec. Times to TOF ratio 0.9 were 114±75 and 186±105 sec in Group 1 and 2, respectively. No serious adverse effects related to sugammadex and to electrical stimulation were reported. No reoccurrence of neuromuscular block was observed. Neurophysiological monitoring using mMEPs confirmed that sugammadex provided a complete recovery from profound and "deep" residual rocuronium-induced neuromuscular blockade.

Robotics, assistive technology, and occupational therapy management to improve upper limb function in pediatric neuromuscular diseases.

PubMed

Rahman, Tariq; Basante, Joseph; Alexander, Michael

2012-08-01

This article presents an overview of occupational therapy assessments and treatment options for individuals with neuromuscular disabilities, with a particular focus on children with neuromuscular disorders. The discussion includes descriptions of standard treatments, commercial adaptive equipment, and homemade adaptive solutions. The state of the art in therapeutic and assistive robots and orthoses for the upper and lower extremity is also provided. Copyright © 2012. Published by Elsevier Inc.

Neuromuscular Coordination Deficit Persists 12 Months after ACL Reconstruction But Can Be Modulated by 6 Weeks of Kettlebell Training: A Case Study in Women's Elite Soccer

PubMed Central

Andersen, Christoffer H.; Bencke, Jesper; Ørntoft, Christina; Linnebjerg, Connie; Hölmich, Per

2017-01-01

The aim of the present single-case study was to investigate the effect of 6 weeks' kettlebell training on the neuromuscular risk profile for ACL injury in a high-risk athlete returning to sport after ACL reconstruction. A female elite soccer player (age 21 years) with no previous history of ACL injury went through neuromuscular screening as measured by EMG preactivity of vastus lateralis and semitendinosus during a standardized sidecutting maneuver. Subsequently, the player experienced a noncontact ACL injury. The player was screened again following postreconstruction rehabilitation, then underwent 6-week kettlebell training, and was subsequently screened again at 6-week follow-up. Prior to and after postreconstruction rehabilitation the player demonstrated a neuromuscular profile during sidecutting known to increase the risk for noncontact ACL injury, that is, reduced EMG preactivity for semitendinosus and elevated EMG preactivity for vastus lateralis. Subsequently, the 6-week kettlebell training increased semitendinosus muscle preactivity during sidecutting by 38 percentage points to a level equivalent to a neuromuscular low-risk profile. An ACL rehabilitated female athlete with a high-risk neuromuscular profile changed to low-risk in response to 6 weeks of kettlebell training. Thus, short-term kettlebell exercise with documented high levels of medial hamstring activation was found to transfer into high medial hamstring preactivation during a sidecutting maneuver. PMID:28197354

[Pollution characteristics of PCBs in electronic waste dismantling areas of Zhejiang province].

PubMed

Wang, Xiaofeng; Lou, Xiaoming; Han, Guangen; Shen, Haitao; Ding, Gangqiang

2011-09-01

To study the pollution level and distribution pattern of polychlorinated biphenyls (PCBs) in the environment media in electronic waste dismantling area of Zhejiang province. Water, soil and PM10 were sampled in electronic waste dismantling areas. The contents, distribution characteristics and toxic equivalents (TEQs) of PCBs in local environment were evaluated by ultra-trace detection methods. The PCBs contents of water, soil and PM10 in Luqiao and Zhenhai, the relatively high polluted areas, were higher than those in Longyou, the control area. The dominant PCBs detected from the environment in Luqiao were hexa-CBs (PCB138 and PCB153), while penta-CBs were dominant in Zhenhai and Longyou. TEQs in electronic waste recycling area were higher than those in control areas. The TEQs of PCBs in water and soil were the highest in Zhenhai, while the TEQs of PM10 were the highest in Luqiao. The local environment has been polluted by PCBs emitted from electronic waste recycling. PCBs pollution monitoring in electronic waste recycling area should be strengthened to prevent PCBs-induced health effects.

Remote Fiber Laser Cutting System for Dismantling Glass Melter - 13071

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitsui, Takashi; Miura, Noriaki; Oowaki, Katsura

Since 2008, the equipment for dismantling the used glass melter has been developed in High-level Liquid Waste (HLW) Vitrification Facility in the Japanese Rokkasho Reprocessing Plant (RRP). Due to the high radioactivity of the glass melter, the equipment requires a fully-remote operation in the vitrification cell. The remote fiber laser cutting system was adopted as one of the major pieces of equipment. An output power of fiber laser is typically higher than other types of laser and so can provide high-cutting performance. The fiber laser can cut thick stainless steel and Inconel, which are parts of the glass melter suchmore » as casings, electrodes and nozzles. As a result, it can make the whole of the dismantling work efficiently done for a shorter period. Various conditions of the cutting test have been evaluated in the process of developing the remote fiber cutting system. In addition, the expected remote operations of the power manipulator with the laser torch have been fully verified and optimized using 3D simulations. (authors)« less

On one modification of traveling salesman problem oriented on application in atomic engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chentsov, A. G.; Sesekin, A. N.; Shcheklein, S. E.

The mathematical model of a problem of minimization of a dose of an irradiation of the personnel which is carrying out dismantling of the completing block of a nuclear power plant is considered. Dismantling of elements of the block is carried out consistently. A brigade of workers having carried out dismantling of the next element of the block passes to similar work on other element of the block. Thus it is supposed that on the sequence of performance of works restrictions are imposed. These restrictions assume that on a number of pairs of works the condition is imposed: the secondmore » work cannot be executed before the first. This problem is similar to a known traveling salesman problem with the difference that expenses function depends on the list of outstanding works, and on sequence of performance of works and corresponding motions the constraints in the form of antecedence are imposed. The variant of the dynamic programming method is developed for such problem and the corresponding software is created.« less

Analysis of Alternatives for Dismantling of the Equipment in Building 117/1 at Ignalina NPP - 13278

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poskas, Povilas; Simonis, Audrius; Poskas, Gintautas

2013-07-01

Ignalina NPP was operating two RBMK-1500 reactors which are under decommissioning now. In this paper dismantling alternatives of the equipment in Building 117/1 are analyzed. After situation analysis and collection of the primary information related to components' physical and radiological characteristics, location and other data, two different alternatives for dismantling of the equipment are formulated - the first (A1), when major components (vessels and pipes of Emergency Core Cooling System - ECCS) are segmented/halved in situ using flame cutting (oxy-acetylene) and the second one (A2), when these components are segmented/halved at the workshop using CAMC (Contact Arc Metal Cutting) technique.more » To select the preferable alternative MCDA method - AHP (Analytic Hierarchy Process) is applied. Hierarchical list of decision criteria, necessary for assessment of alternatives performance, are formulated. Quantitative decision criteria values for these alternatives are calculated using software DECRAD, which was developed by Lithuanian Energy Institute Nuclear engineering laboratory. While qualitative decision criteria are evaluated using expert judgment. Analysis results show that alternative A1 is better than alternative A2. (authors)« less

Treating pediatric neuromuscular disorders: The future is now

PubMed Central

D. Gonorazky, Hernan; Cohn, Ronald D.; Campbell, Craig

2017-01-01

Pediatric neuromuscular diseases encompass all disorders with onset in childhood and where the primary area of pathology is in the peripheral nervous system. These conditions are largely genetic in etiology, and only those with a genetic underpinning will be presented in this review. This includes disorders of the anterior horn cell (e.g., spinal muscular atrophy), peripheral nerve (e.g., Charcot–Marie–Tooth disease), the neuromuscular junction (e.g., congenital myasthenic syndrome), and the muscle (myopathies and muscular dystrophies). Historically, pediatric neuromuscular disorders have uniformly been considered to be without treatment possibilities and to have dire prognoses. This perception has gradually changed, starting in part with the discovery and widespread application of corticosteroids for Duchenne muscular dystrophy. At present, several exciting therapeutic avenues are under investigation for a range of conditions, offering the potential for significant improvements in patient morbidities and mortality and, in some cases, curative intervention. In this review, we will present the current state of treatment for the most common pediatric neuromuscular conditions, and detail the treatment strategies with the greatest potential for helping with these devastating diseases. PMID:28889642

Effectiveness of deep versus moderate muscle relaxation during laparoscopic donor nephrectomy in enhancing postoperative recovery: study protocol for a randomized controlled study.

PubMed

Bruintjes, Moira H D; Braat, Andries E; Dahan, Albert; Scheffer, Gert-Jan; Hilbrands, Luuk B; d'Ancona, Frank C H; Donders, Rogier A R T; van Laarhoven, Cornelis J H M; Warlé, Michiel C

2017-03-04

Postoperative recovery after live donor nephrectomy is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade has been shown to reduce postoperative pain scores after laparoscopic surgery. In this study, we will investigate whether deep neuromuscular blockade also improves the early quality of recovery after live donor nephrectomy. The RELAX-study is a phase IV, multicenter, double-blinded, randomized controlled trial, in which 96 patients, scheduled for living donor nephrectomy, will be randomized into two groups: one with deep and one with moderate neuromuscular blockade. Deep neuromuscular blockade is defined as a post-tetanic count of 1-2. Our primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 24 h after extubation. This study is, to our knowledge, the first randomized study to assess the effectiveness of deep neuromuscular blockade during laparoscopic donor nephrectomy in enhancing postoperative recovery. The study findings may also be applicable for other laparoscopic procedures. clinicaltrials.gov, NCT02838134 . Registered on 29 June 2016.

Impact of exercise-induced fatigue on the strength, postural control, and gait of children with a neuromuscular disease.

PubMed

Hart, Raphael; Ballaz, Laurent; Robert, Maxime; Pouliot, Annie; D'Arcy, Sylvie; Raison, Maxime; Lemay, Martin

2014-08-01

Children with a neuromuscular disease are prone to early muscular fatigue. The objective of the present study was to evaluate the effects of fatigue induced by a walking exercise on the strength, postural control, and gait of children with a neuromuscular disease. Maximal isometric knee strength (extension and flexion), quiet standing postural control, and gait were evaluated in 12 children (8.8 [1.4] yrs) with a neuromuscular disease before and after a walking exercise. The participants were asked to stop walking when they considered themselves "very fatigued." After the exercise-induced fatigue, a significant increase in range of motion in pelvis obliquity, hip abduction and adduction, and ankle flexion and extension during gait was reported along with an increase in stride length variability. Fatigue also reduced the knee flexor strength and had a detrimental effect on postural control. Fatigue affects the strength, postural control, and gait of children with a neuromuscular disease and could notably increase the risks of falling and the occurrence of serious injuries.

Modeling and Identification of a Realistic Spiking Neural Network and Musculoskeletal Model of the Human Arm, and an Application to the Stretch Reflex.

PubMed

Sreenivasa, Manish; Ayusawa, Ko; Nakamura, Yoshihiko

2016-05-01

This study develops a multi-level neuromuscular model consisting of topological pools of spiking motor, sensory and interneurons controlling a bi-muscular model of the human arm. The spiking output of motor neuron pools were used to drive muscle actions and skeletal movement via neuromuscular junctions. Feedback information from muscle spindles were relayed via monosynaptic excitatory and disynaptic inhibitory connections, to simulate spinal afferent pathways. Subject-specific model parameters were identified from human experiments by using inverse dynamics computations and optimization methods. The identified neuromuscular model was used to simulate the biceps stretch reflex and the results were compared to an independent dataset. The proposed model was able to track the recorded data and produce dynamically consistent neural spiking patterns, muscle forces and movement kinematics under varying conditions of external forces and co-contraction levels. This additional layer of detail in neuromuscular models has important relevance to the research communities of rehabilitation and clinical movement analysis by providing a mathematical approach to studying neuromuscular pathology.

Imaging of respiratory muscles in neuromuscular disease: A review.

PubMed

Harlaar, L; Ciet, P; van der Ploeg, A T; Brusse, E; van der Beek, N A M E; Wielopolski, P A; de Bruijne, M; Tiddens, H A W M; van Doorn, P A

2018-03-01

Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease. Copyright © 2017. Published by Elsevier B.V.

Arterial Ventricular Uncoupling with Age and Disease and Recoupling with Exercise

PubMed Central

Chantler, Paul D

2017-01-01

The deterioration in arterial and cardiac function with aging impairs arterial ventricular coupling, an important determinant of cardiovascular performance. However, exercise training improves arterial ventricular coupling especially during exercise during the age and disease process. This review examines the concept of arterial-ventricular coupling, and how age, and disease uncouples but exercise training recouples the heart and arterial system. PMID:28072585

Neuromuscular Scoliosis

MedlinePlus

... degree of neuromuscular involvement. Diagnosis Incidence of Scoliosis Cerebral palsy (2 limbs involved) 25% Myelodysplasia (lower lumbar) 60% Spinal muscle atrophy 67% Friedreich ataxia 80% Cerebral palsy (4 limbs involved) 80% Duchenne muscular dystrophy 90% ...

Radiation Hardened Telerobotic Dismantling System Development Final Report CRADA No. TC-1340-96

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, C.; Lightman, A.

This project was a collaborative effort between the University of California, LLNL and RedZone Robotics, Inc. for the development of radiation-hardened telerobotic dismantling systems for use in applications such as nuclear facility remediation, nuclear accident response, and Chemobyltype remediation. The project supported the design, development, fabrication and testing of a Ukrainian robotic systems. The project was completed on time and within budget. All deliverables were completed. The final project deliverables were consistent with the plans developed in the original project with the exception that the fabricated systems remained in Ukraine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carvo, Alan E.

Between the mid-1970s and the mid-1980s Sandia National Laboratory constructed eleven experimental assemblies to simulate debris beds formed in a sodium-cooled fast breeder reactor. All but one of the assemblies were irradiated. The experimental assemblies were transferred to the Idaho National Laboratory (INL) in 2007 and 2008 for storage, dismantlement, recovery of the uranium for reuse in the nuclear fuel cycle, and disposal of unneeded materials. This paper addresses the effort to dismantle the assemblies down to the primary containment vessel and repackage them for temporary storage until such time as equipment necessary for sodium separation is in place.

Uncoupling of oxidative phosphorylation and Smac/DIABLO release are not sufficient to account for induction of apoptosis by sulindac sulfide in human colorectal cancer cells.

PubMed

Daouphars, Mikael; Koufany, Meriem; Benani, Alexandre; Marchal, Sophie; Merlin, Jean-Louis; Netter, Patrick; Jouzeau, Jean-Yves

2005-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have shown chemopreventive properties in colorectal cancer, involving both cyclooxygenase (COX)-dependent and -independent mechanisms. Apart from their selectivity for COX isoenzymes, NSAIDs differ in their acidic character which supports ability to uncouple oxidative phosphorylation. To assess the possible contribution of uncoupling to their antineoplastic properties, we compared the effect of sulindac sulfide (SS), an acidic NSAID and NS-398, a non-acidic tricyclic, on mitochondrial function and apoptosis in colorectal cancer cell lines (HT29, Caco-2, HCT15 and HCT116). Although cell lines displayed a different COX status, SS and NS-398 caused growth arrest in a dose-related manner. High dose (10(-4)M) of SS but not of NS-398, increased the percentage of subG1 cell population while reducing mitochondrial transmembrane potential (DeltaPsim). Cyclosporin A (CsA, 1 microM) prevented collapse of DeltaPsim induced by 10(-4)M SS but not by 7.5 microM FCCP used as a protonophoric control. SS and FCCP increased the cytosolic release of Smac/DIABLO which was differently affected by CsA pretreatment depending on the uncoupler. Finally, 7.5 microM FCCP failed to induce apoptosis whereas CsA prevented apoptosis induced by SS from 16% in HCT15 to 41% in HCT116. The present study shows that despite the ability of sulindac sulfide to behave as a protonophoric uncoupler, CsA-sensitive opening of mitochondrial permeability transition pore contributes little to its pro-apoptotic effect in colorectal cancer cells.

Derivatives of Rhodamine 19 as Mild Mitochondria-targeted Cationic Uncouplers*

PubMed Central

Antonenko, Yuri N.; Avetisyan, Armine V.; Cherepanov, Dmitry A.; Knorre, Dmitry A.; Korshunova, Galina A.; Markova, Olga V.; Ojovan, Silvia M.; Perevoshchikova, Irina V.; Pustovidko, Antonina V.; Rokitskaya, Tatyana I.; Severina, Inna I.; Simonyan, Ruben A.; Smirnova, Ekaterina A.; Sobko, Alexander A.; Sumbatyan, Natalia V.; Severin, Fedor F.; Skulachev, Vladimir P.

2011-01-01

A limited decrease in mitochondrial membrane potential can be beneficial for cells, especially under some pathological conditions, suggesting that mild uncouplers (protonophores) causing such an effect are promising candidates for therapeutic uses. The great majority of protonophores are weak acids capable of permeating across membranes in their neutral and anionic forms. In the present study, protonophorous activity of a series of derivatives of cationic rhodamine 19, including dodecylrhodamine (C12R1) and its conjugate with plastoquinone (SkQR1), was revealed using a variety of assays. Derivatives of rhodamine B, lacking dissociable protons, showed no protonophorous properties. In planar bilayer lipid membranes, separating two compartments differing in pH, diffusion potential of H+ ions was generated in the presence of C12R1 and SkQR1. These compounds induced pH equilibration in liposomes loaded with the pH probe pyranine. C12R1 and SkQR1 partially stimulated respiration of rat liver mitochondria in State 4 and decreased their membrane potential. Also, C12R1 partially stimulated respiration of yeast cells but, unlike the anionic protonophore FCCP, did not suppress their growth. Loss of function of mitochondrial DNA in yeast (grande-petite transformation) is known to cause a major decrease in the mitochondrial membrane potential. We found that petite yeast cells are relatively more sensitive to the anionic uncouplers than to C12R1 compared with grande cells. Together, our data suggest that rhodamine 19-based cationic protonophores are self-limiting; their uncoupling activity is maximal at high membrane potential, but the activity decreases membrane potentials, which causes partial efflux of the uncouplers from mitochondria and, hence, prevents further membrane potential decrease. PMID:21454507

On the causes and consequences of the uncoupler-like effects of quercetin and dehydrosilybin in H9c2 cells

PubMed Central

Mouithys-Mickalad, Ange; Dostal, Zdenek; Serteyn, Didier; Modriansky, Martin

2017-01-01

Quercetin and dehydrosilybin are polyphenols which are known to behave like uncouplers of respiration in isolated mitochondria. Here we investigated whether the effect is conserved in whole cells. Following short term incubation, neither compound uncouples mitochondrial respiration in whole H9c2 cells below 50μM. However, following hypoxia, or long term incubation, leak (state IV with oligomycin) oxygen consumption is increased by quercetin. Both compounds partially protected complex I respiration, but not complex II in H9c2 cells following hypoxia. In a permeabilised H9c2 cell model, the increase in leak respiration caused by quercetin is lowered by increased [ADP] and is increased by adenine nucleotide transporter inhibitor, atractyloside, but not bongkrekic acid. Both quercetin and dehydrosilybin dissipate mitochondrial membrane potential in whole cells. In the case of quercetin, the effect is potentiated post hypoxia. Genetically encoded Ca++ sensors, targeted to the mitochondria, enabled the use of fluorescence microscopy to show that quercetin decreased mitochondrial [Ca++] while dehydrosilybin did not. Likewise, quercetin decreases accumulation of [Ca++] in mitochondria following hypoxia. Fluorescent probes were used to show that both compounds decrease plasma membrane potential and increase cytosolic [Ca++]. We conclude that the uncoupler-like effects of these polyphenols are attenuated in whole cells compared to isolated mitochondria, but downstream effects are nevertheless apparent. Results suggest that the effect of quercetin observed in whole and permeabilised cells may originate in the mitochondria, while the mechanism of action of cardioprotection by dehydrosilybin may be less dependent on mitochondrial uncoupling than originally thought. Rather, protective effects may originate due to interactions at the plasma membrane. PMID:28977033

Correlation between uncoupled ATP hydrolysis and heat production by the sarcoplasmic reticulum Ca2+-ATPase: coupling effect of fluoride.

PubMed

Reis, M; Farage, M; de Souza, A C; de Meis, L

2001-11-16

The sarcoplasmic reticulum Ca(2+)-ATPase transports Ca(2+) using the chemical energy derived from ATP hydrolysis. Part of the chemical energy is used to translocate Ca(2+) through the membrane (work) and part is dissipated as heat. The amount of heat produced during catalysis increases after formation of the Ca(2+) gradient across the vesicle membrane. In the absence of gradient (leaky vesicles) the amount of heat produced/mol of ATP cleaved is half of that measured in the presence of the gradient. After formation of the gradient, part of the ATPase activity is not coupled to Ca(2+) transport. We now show that NaF can impair the uncoupled ATPase activity with discrete effect on the ATPase activity coupled to Ca(2+) transport. For the control vesicles not treated with NaF, after formation of the gradient only 20% of the ATP cleaved is coupled to Ca(2+) transport, and the caloric yield of the total ATPase activity (coupled plus uncoupled) is 22.8 kcal released/mol of ATP cleaved. In contrast, the vesicles treated with NaF consume only the ATP needed to maintain the gradient, and the caloric yield of ATP hydrolysis is 3.1 kcal/mol of ATP. The slow ATPase activity measured in vesicles treated with NaF has the same Ca(2+) dependence as the control vesicles. This demonstrates unambiguously that the uncoupled activity is an actual pathway of the Ca(2+)-ATPase rather than a contaminating phosphatase. We conclude that when ATP hydrolysis occurs without coupled biological work most of the chemical energy is dissipated as heat. Thus, uncoupled ATPase activity appears to be the mechanistic feature underlying the ability of the Ca(2+)-ATPase to modulated heat production.

Overview of Remote Handling Equipment Used for the NPP A1 Decommissioning - 12141

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kravarik, K.; Medved, J.; Pekar, A.

The first Czechoslovak NPP A1 was in operation from 1972 to 1977 and it was finally shutdown due to an accident (level 4 according to the INES). The presence of radioactive, toxic or hazardous materials limits personnel access to facilities and therefore it is necessary to use remote handling technologies for some most difficult characterization, retrieval, decontamination and dismantling tasks. The history of remote handling technologies utilization started in nineties when the spent nuclear fuel, including those fuel assemblies damaged during the accident, was prepared for the transport to Russia. Subsequent significant development of remote handling equipment continued during implementationmore » of the NPP A1 decommissioning project - Stage I and ongoing Stage II. Company VUJE, Inc. is the general contractor for both mentioned stages of the decommissioning project. Various remote handling manipulators and robotics arms were developed and used. It includes remotely controlled vehicle manipulator MT-15 used for characterisation tasks in hostile and radioactive environment, special robust manipulator DENAR-41 used for the decontamination of underground storage tanks and multi-purposes robotics arms MT-80 and MT-80A developed for variety of decontamination and dismantling tasks. The heavy water evaporator facility dismantling is the current task performed remotely by robotics arm MT-80. The heavy water evaporator is located inside the main production building in the room No. 220 where loose surface contamination varies from 10 Bq/cm{sup 2} to 1x10{sup 3} Bq/cm{sup 2}, dose rate is up to 1.5 mGy/h and the feeding pipeline contained liquid RAW with high tritium content. Presented manipulators have been designed for broad range of decommissioning tasks. They are used for recognition, sampling, waste retrieval from large underground tanks, decontamination and dismantling of technological equipments. Each of the mentioned fields claims specific requirements on design of manipulator, their operation and control systems as well as tools of manipulators. Precise planning of decontamination and dismantling tasks is necessary for its successful performance by remotely controlled manipulator. The example of the heavy water evaporator demonstrates typical procedure for decommissioning of contaminated technological equipment by remotely controlled manipulators - planning of decommissioning tasks, preparatory tasks, modification of applied tools and design of specific supporting constructions for manipulator and finally decontamination and dismantling themselves. Due to the particularly demanding conditions in highly contaminated A1 NPP, a team of experts with special know-how in the field of decommissioning has grown up, and unique technological equipment enabling effective and safe work in environment with a high radiation level has been developed. (authors)« less

Intractable Polyuria Mimicking Diabetes Insipidus-Source Traced to Vecuronium Infusion.

PubMed

Haldar, Rudrashish; Samanta, Sukhen; Singla, Ankush

2016-01-01

Continuous infusion of vecuronium is a commonly used technique for patients requiring prolonged neuromuscular blockade for mechanical ventilation. As compared with older neuromuscular blocking agents, it confers the advantages of rapid excretion and intermediate duration of action. Prolongation of neuromuscular blockade and muscle weakness are the known complications of continuous vecuronium infusion. This report attempts to describe polyuria, as a hitherto unknown complication of vecuronium infusion, which can occur due to the mannitol present in commercially available preparation of vecuronium bromide.

Neuromuscular disorders in the intensive care unit.

PubMed

Marinelli, William A; Leatherman, James W

2002-10-01

Neuromuscular disorders encountered in the ICU can be categorized as muscular diseases that lead to ICU admission and those that are acquired in the ICU. This article discusses three neuromuscular disorders can lead to ICU admission and have a putative immune-mediated pathogenesis: the Guillian-Barré syndrome, myasthenia gravis, and dermatomyositis/polymyositis. It also reviews critical care polyneuropathy and ICU acquired myopathy, two disorders that, alone or in combination, are responsible for nearly all cases of severe ICU acquired muscle weakness.

21 CFR 888.1240 - AC-powered dynamometer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... neuromuscular function or degree of neuromuscular blockage by measuring, with a force transducer (a device that translates force into electrical impulses), the grip-strength of a patient's hand. (b) Classification. Class...

21 CFR 888.1240 - AC-powered dynamometer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... neuromuscular function or degree of neuromuscular blockage by measuring, with a force transducer (a device that translates force into electrical impulses), the grip-strength of a patient's hand. (b) Classification. Class...

Effects of whole body vibration exercise on neuromuscular function for individuals with knee osteoarthritis: study protocol for a randomized controlled trial.

PubMed

Lai, Zhangqi; Wang, Xueqiang; Lee, Seullee; Hou, Xihe; Wang, Lin

2017-09-20

Knee osteoarthritis (KOA) is a leading cause of public disability. Neuromuscular function contributes to the development and/or progression of KOA. Whole body vibration (WBV) exercise improve the neuromuscular function of patients with neurological disorders and even that of older patients with limited exercise options. Therefore, WBV exercise may offer an efficient and alternative treatment for individuals with KOA. However, the effects of WBV training on the neuromuscular function of individuals with KOA remain unclear. Therefore, this study attempts to investigate the effect of a 12-week WBV exercise on the neuromuscular function of individuals with KOA. We will conduct a prospective, single-blind randomized controlled trial on 180 KOA patients. Participants will be randomly assigned to the WBV exercise, lower extremity resistance training, and health education groups. The WBV exercise group will participate in a 12-week WBV training. The lower extremity resistance training group will undergo a 12-week lower extremity resistance training of both lower limbs. The control group will receive health education for 12 weeks. After the intervention, the participants will be followed up for 3 months with no active intervention. Primary outcome measures will include anthropometric measurements, gait analysis during walking and stair climbing, muscle strength test of the knee and ankle, proprioception test of the knee and ankle, and neuromuscular response of the leg muscles. Secondary outcome measures will include self-reported pain and physical functional capacity, and physical performance measures. Furthermore, adverse events will be recorded and analyzed. If any participant withdraws from the trial, intention-to-treat analysis will be performed. Important features of this trial mainly include intervention setting, outcome measure selection, and study duration. This study is intended for estimating the effect of WBV intervention on neuromuscular control outcomes. Study results may provide evidence to support the beneficial effects of WBV exercise on the physical performance and neuromuscular control of individuals with KOA to fill the research gap on the efficacy of WBV. Chinese Clinical Trial Registry, ID: ChiCTR-IOR-16009234 . Registered on 21 September 2016.

Dynamic Neuromuscular Control of the Lower Limbs in Response to Unexpected Single-Planar versus Multi-Planar Support Perturbations in Young, Active Adults.

PubMed

Malfait, Bart; Staes, Filip; de Vries, Aijse; Smeets, Annemie; Hawken, Malcolm; Robinson, Mark A; Vanrenterghem, Jos; Verschueren, Sabine

2015-01-01

An anterior cruciate ligament (ACL) injury involves a multi-planar injury mechanism. Nevertheless, unexpected multi-planar perturbations have not been used to screen athletes in the context of ACL injury prevention yet could reveal those more at risk. The objective of this study was to compare neuromuscular responses to multi-planar (MPP) and single-planar perturbations (SPP) during a stepping-down task. These results might serve as a basis for future implementation of external perturbations in ACL injury screening programs. Thirteen young adults performed a single leg stepping-down task in eight conditions (four MPP and four SPP with a specified amplitude and velocity). The amplitudes of vastus lateralis (VL), vastus medialis (VM), hamstrings lateralis (HL), hamstrings medialis (HM) EMG activity, medio-lateral and anterior-posterior centre of mass (COM) displacements, the peak knee flexion and abduction angles were compared between conditions using an one-way ANOVA. Number of stepping responses were monitored during all conditions. Significantly greater muscle activity levels were found in response to the more challenging MPP and SPP compared to the less challenging conditions (p < 0.05). No differences in neuromuscular activity were found between the MPP conditions and their equivalents in the SPP. Eighteen stepping responses were monitored in the SPP versus nine in the MPP indicating that the overall neuromuscular control was even more challenged during the SPP which was supported by greater COM displacements in the SPP. The more intense MPP and SPP evoked different neuromuscular responses resulting in greater muscle activity levels compared to small perturbations. Based on the results of COM displacements and based on the amount of stepping responses, dynamic neuromuscular control of the knee joint appeared less challenged during the MPP. Therefore, future work should investigate extensively if other neuromuscular differences (i.e. co-activation patterns and kinetics) exist between MPP and SPP. In addition, future work should examine the influence on the neuromuscular control of the magnitude of the perturbations and the magnitude of stepping height and stepping distance.

Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

ClinicalTrials.gov

2015-08-24

Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

Derivation of equations of motion for multi-blade rotors employing coupled modes and including high twist capability

NASA Technical Reports Server (NTRS)

Sopher, R.

1975-01-01

The equations of motion are derived for a multiblade rotor. A high twist capability and coupled flatwise-edgewise assumed normal modes are employed instead of uncoupled flatwise - edgewise assumed normal models. The torsion mode is uncoupled. Support system models, consisting of complete helicopters in free flight, or grounded flexible supports, arbitrary rotor-induced inflow, and arbitrary vertical gust models are also used.

Short-term consumption of a high-fat diet impairs whole-body efficiency and cognitive function in sedentary men.

PubMed

Edwards, Lindsay M; Murray, Andrew J; Holloway, Cameron J; Carter, Emma E; Kemp, Graham J; Codreanu, Ion; Brooker, Helen; Tyler, Damian J; Robbins, Peter A; Clarke, Kieran

2011-03-01

We recently showed that a short-term high-fat diet blunted exercise performance in rats, accompanied by increased uncoupling protein levels and greater respiratory uncoupling. In this study, we investigated the effects of a similar diet on physical and cognitive performance in humans. Twenty sedentary men were assessed when consuming a standardized, nutritionally balanced diet (control) and after 7 d of consuming a diet comprising 74% kcal from fat. Efficiency was measured during a standardized exercise task, and cognition was assessed using a computerized assessment battery. Skeletal muscle mitochondrial function was measured using (31)P magnetic resonance spectroscopy. The diet increased mean ± se plasma free fatty acids by 44% (0.32±0.03 vs. 0.46±0.05 mM; P<0.05) and decreased whole-body efficiency by 3% (21±1 vs. 18±1%; P<0.05), although muscle uncoupling protein (UCP3) content and maximal mitochondrial function were unchanged. High-fat diet consumption also increased subjects' simple reaction times (P<0.01) and decreased power of attention (P<0.01). Thus, we have shown that a high-fat diet blunts whole-body efficiency and cognition in sedentary men. We suggest that this effect may be due to increased respiratory uncoupling.

On the effect of acoustic coupling on random and harmonic plate vibrations

NASA Technical Reports Server (NTRS)

Frendi, A.; Robinson, J. H.

1993-01-01

The effect of acoustic coupling on random and harmonic plate vibrations is studied using two numerical models. In the coupled model, the plate response is obtained by integration of the nonlinear plate equation coupled with the nonlinear Euler equations for the surrounding acoustic fluid. In the uncoupled model, the nonlinear plate equation with an equivalent linear viscous damping term is integrated to obtain the response of the plate subject to the same excitation field. For a low-level, narrow-band excitation, the two models predict the same plate response spectra. As the excitation level is increased, the response power spectrum predicted by the uncoupled model becomes broader and more shifted towards the high frequencies than that obtained by the coupled model. In addition, the difference in response between the coupled and uncoupled models at high frequencies becomes larger. When a high intensity harmonic excitation is used, causing a nonlinear plate response, both models predict the same frequency content of the response. However, the level of the harmonics and subharmonics are higher for the uncoupled model. Comparisons to earlier experimental and numerical results show that acoustic coupling has a significant effect on the plate response at high excitation levels. Its absence in previous models may explain the discrepancy between predicted and measured responses.

Salsalate (Salicylate) Uncouples Mitochondria, Improves Glucose Homeostasis, and Reduces Liver Lipids Independent of AMPK-β1

PubMed Central

Smith, Brennan K.; Ford, Rebecca J.; Desjardins, Eric M.; Green, Alex E.; Hughes, Meghan C.; Houde, Vanessa P.; Day, Emily A.; Marcinko, Katarina; Crane, Justin D.; Mottillo, Emilio P.; Perry, Christopher G.R.; Kemp, Bruce E.; Tarnopolsky, Mark A.; Steinberg, Gregory R.

2017-01-01

Salsalate is a prodrug of salicylate that lowers blood glucose in patients with type 2 diabetes (T2D) and reduces nonalcoholic fatty liver disease (NAFLD) in animal models; however, the mechanism mediating these effects is unclear. Salicylate directly activates AMPK via the β1 subunit, but whether salsalate requires AMPK-β1 to improve T2D and NAFLD has not been examined. Therefore, wild-type (WT) and AMPK-β1–knockout (AMPK-β1KO) mice were treated with a salsalate dose resulting in clinically relevant serum salicylate concentrations (~1 mmol/L). Salsalate treatment increased VO2, lowered fasting glucose, improved glucose tolerance, and led to an ~55% reduction in liver lipid content. These effects were observed in both WT and AMPK-β1KO mice. To explain these AMPK-independent effects, we found that salicylate increases oligomycin-insensitive respiration (state 4o) and directly increases mitochondrial proton conductance at clinical concentrations. This uncoupling effect is tightly correlated with the suppression of de novo lipogenesis. Salicylate is also able to stimulate brown adipose tissue respiration independent of uncoupling protein 1. These data indicate that the primary mechanism by which salsalate improves glucose homeostasis and NAFLD is via salicylate-driven mitochondrial uncoupling. PMID:27554471

Role of Dietary Antioxidants in the Preservation of Vascular Function and the Modulation of Health and Disease

PubMed Central

Varadharaj, Saradhadevi; Kelly, Owen J.; Khayat, Rami N.; Kumar, Purnima S.; Ahmed, Naseer; Zweier, Jay L.

2017-01-01

In vascular diseases, including hypertension and atherosclerosis, vascular endothelial dysfunction (VED) occurs secondary to altered function of endothelial nitric oxide synthase (eNOS). A novel redox regulated pathway was identified through which eNOS is uncoupled due to S-glutathionylation of critical cysteine residues, resulting in superoxide free radical formation instead of the vasodilator molecule, nitric oxide. In addition, the redox sensitive cofactor tetrahydrobiopterin, BH4, is also essential for eNOS coupling. Antioxidants, either individually or combined, can modulate eNOS uncoupling by scavenging free radicals or impairing specific radical generating pathways, thus preventing oxidative stress and ameliorating VED. Epidemiological evidence and dietary guidelines suggest that diets high in antioxidants, or antioxidant supplementation, could preserve vascular health and prevent cardiovascular diseases (CVDs). Therefore, the purpose of this review is to highlight the possible role of dietary antioxidants in regulating eNOS function and uncoupling which is critical for maintenance of vascular health with normal blood flow/circulation and prevention of VED. We hypothesize that a conditioned dietary approach with suitable antioxidants may limit systemic oxidation, maintain a beneficial ratio of reduced to oxidized glutathione, and other redox markers, and minimize eNOS uncoupling serving to prevent CVD and possibly other chronic diseases. PMID:29164133

Influence of stochastic sea ice parametrization on climate and the role of atmosphere–sea ice–ocean interaction

PubMed Central

Juricke, Stephan; Jung, Thomas

2014-01-01

The influence of a stochastic sea ice strength parametrization on the mean climate is investigated in a coupled atmosphere–sea ice–ocean model. The results are compared with an uncoupled simulation with a prescribed atmosphere. It is found that the stochastic sea ice parametrization causes an effective weakening of the sea ice. In the uncoupled model this leads to an Arctic sea ice volume increase of about 10–20% after an accumulation period of approximately 20–30 years. In the coupled model, no such increase is found. Rather, the stochastic perturbations lead to a spatial redistribution of the Arctic sea ice thickness field. A mechanism involving a slightly negative atmospheric feedback is proposed that can explain the different responses in the coupled and uncoupled system. Changes in integrated Antarctic sea ice quantities caused by the stochastic parametrization are generally small, as memory is lost during the melting season because of an almost complete loss of sea ice. However, stochastic sea ice perturbations affect regional sea ice characteristics in the Southern Hemisphere, both in the uncoupled and coupled model. Remote impacts of the stochastic sea ice parametrization on the mean climate of non-polar regions were found to be small. PMID:24842027

Clusianone, a naturally occurring nemorosone regioisomer, uncouples rat liver mitochondria and induces HepG2 cell death.

PubMed

Reis, Felippe H Z; Pardo-Andreu, Gilberto L; Nuñez-Figueredo, Yanier; Cuesta-Rubio, Osmany; Marín-Prida, Javier; Uyemura, Sérgio A; Curti, Carlos; Alberici, Luciane C

2014-04-05

Clusianone is a member of the polycyclic polyprenylated acylphloroglucinol family of natural products; its cytotoxic mechanism is unknown. Clusianone is a structural isomer of nemorosone, which is a mitochondrial uncoupler and a well-known cytotoxic anti-cancer agent; thus, we addressed clusianone action at the mitochondria and its potential cytotoxic effects on cancer cells. In the HepG2 hepatocarcinoma cell line, clusianone induced mitochondrial membrane potential dissipation, ATP depletion and phosphatidyl serine externalization; this later event is indicative of apoptosis induction. In isolated mitochondria from rat liver, clusianone promoted protonophoric mitochondrial uncoupling. This was evidenced by the dissipation of mitochondrial membrane potential, an increase in resting respiration, an inhibition of Ca(2+) influx, stimulation of Ca(2+) efflux in Ca(2+)-loaded mitochondria, a decrease in ATP and NAD(P)H levels, generation of ROS, and swelling of valinomycin-treated organelles in hyposmotic potassium acetate media. The cytotoxic and uncoupling actions of clusianone were appreciably less than those of nemorosone, likely due to the presence of an intra-molecular hydrogen bond with the juxtaposed carbonyl group at the C15 position. Therefore, clusianone is capable of pharmacologically increasing the leakage of protons from the mitochondria and with favorable cytotoxicity in relation to nemorosone. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

ZmPUMP encodes a fully functional monocot plant uncoupling mitochondrial protein whose affinity to fatty acid is increased with the introduction of a His pair at the second matrix loop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Favaro, Regiane Degan; Borecky, Jiri; Colombi, Debora

Uncoupling proteins (UCPs) are specialized mitochondrial transporter proteins that uncouple respiration from ATP synthesis. In this study, cDNA encoding maize uncoupling protein (ZmPUMP) was expressed in Escherichia coli and recombinant ZmPUMP reconstituted in liposomes. ZmPUMP activity was associated with a linoleic acid (LA)-mediated H{sup +} efflux with K {sub m} of 56.36 {+-} 0.27 {mu}M and V {sub max} of 66.9 {mu}mol H{sup +} min{sup -1} (mg prot){sup -1}. LA-mediated H{sup +} fluxes were sensitive to ATP inhibition with K {sub i} of 2.61 {+-} 0.36 mM (at pH 7.2), a value similar to those for dicot UCPs. ZmPUMP wasmore » also used to investigate the importance of a histidine pair present in the second matrix loop of mammalian UCP1 and absent in plant UCPs. ZmPUMP with introduced His pair (Lys155His and Ala157His) displayed a 1.55-fold increase in LA-affinity while its activity remained unchanged. Our data indicate conserved properties of plant UCPs and suggest an enhancing but not essential role of the histidine pair in proton transport mechanism.« less

American Association of Neuromuscular & Electrodiagnostic Medicine

MedlinePlus

... on diagnostic approaches to neuromuscular diseases. We recommend Principles of Clinical Electromyography Case Studies. Learn more Enhance ... offers your company the chance to meet its marketing objectives through participation at the AANEM Annual Meeting ...

Unlike myofibers, neuromuscular junctions remain stable during prolonged muscle unloading.

PubMed

Deschenes, Michael R; Will, Kristin M; Booth, Frank W; Gordon, Scott E

2003-06-15

This study assessed the effect of muscle unloading on the neuromuscular system. Sixteen male Fischer 344 rats were randomly assigned to either a hindlimb suspension (unloaded) or control group (N=8/group) for 16 days. Following this intervention period, pre- and postsynaptic features of the neuromuscular junctions (NMJs) of soleus muscles were stained with cytofluorescent techniques, and myofibers were histochemically stained for ATPase activity. The data indicate that 16 days of muscle unloading resulted in significant (P<0.05) atrophy among myofibers (>50%) that was evident among all three major fiber types (I, IIA and IIX), but failed to significantly alter any aspect of NMJ morphology quantified. These results demonstrate an impressive degree of NMJ resilience despite dramatic remodeling of associated myofibers. This may be of benefit during post-unloading rehabilitative measures where effective neuromuscular communication is essential.

The use of in-flight foot pressure as a countermeasure to neuromuscular degradation

NASA Technical Reports Server (NTRS)

Layne, C. S.; Mulavara, A. P.; Pruett, C. J.; McDonald, P. V.; Kozlovskaya, I. B.; Bloomberg, J. J.

1998-01-01

The purpose of this study was to determine whether applying foot pressure to unrestrained subjects during space flight could enhance the neuromuscular activation associated with rapid arm movements. Four men performed unilateral arm raises while wearing--or not wearing--specially designed boots during a 81- or 115-day space flight. Arm acceleration and surface EMG were obtained from selected lower limb and trunk muscles. Pearson r coefficients were used to evaluate similarity in phasic patterns between the two in-flight conditions. In-flight data also were magnitude normalized to the mean voltage value of the muscle activation waveforms obtained during the no-foot-pressure condition to facilitate comparison of activation amplitude between the two in-flight conditions. Foot pressure enhanced neuromuscular activation and somewhat modified the phasic features of the neuromuscular activation during the arm raises.

Autoimmune Neuromuscular Disorders

PubMed Central

Kraker, Jessica; Živković, Saša A

2011-01-01

Autoimmune neuromuscular disorders affecting peripheral nerves, neuromuscular junction or muscle have a wide clinical spectrum with diverse pathogenetic mechanisms. Peripheral nervous system may be targeted in the context of complex immune reactions involving different cytokines, antigen-presenting cells, B cells and different types of T cells. Various immunomodulating and cytotoxic treatments block proliferation or activation of immune cells by different mechanisms attempting to control the response of the immune system and limit target organ injury. Most treatment protocols for autoimmune neuromuscular disorders are based on the use of corticosteroids, intravenous immunoglobulins and plasmapheresis, with cytotoxic agents mostly used as steroid-sparing medications. More recently, development of specific monoclonal antibodies targeting individual cell types allowed a different approach targeting specific immune pathways, but these new treatments are also associated with various adverse effects and their long-term efficacy is still unknown. PMID:22379454

Total hip arthroplasty in patients with neuromuscular imbalance.

PubMed

Konan, S; Duncan, C P

2018-01-01

Patients with neuromuscular imbalance who require total hip arthroplasty (THA) present particular technical problems due to altered anatomy, abnormal bone stock, muscular imbalance and problems of rehabilitation. In this systematic review, we studied articles dealing with THA in patients with neuromuscular imbalance, published before April 2017. We recorded the demographics of the patients and the type of neuromuscular pathology, the indication for surgery, surgical approach, concomitant soft-tissue releases, the type of implant and bearing, pain and functional outcome as well as complications and survival. Recent advances in THA technology allow for successful outcomes in these patients. Our review suggests excellent benefits for pain relief and good functional outcome might be expected with a modest risk of complication. Cite this article: Bone Joint J 2018;100-B(1 Supple A):17-21. ©2018 The British Editorial Society of Bone & Joint Surgery.

Autosomal-dominant non-autoimmune hyperthyroidism presenting with neuromuscular symptoms.

PubMed

Elgadi, Aziz; Arvidsson, C-G; Janson, Annika; Marcus, Claude; Costagliola, Sabine; Norgren, Svante

2005-08-01

Neuromuscular presentations are common in thyroid disease, although the mechanism is unclear. In the present study, we investigated the pathogenesis in a boy with autosomal-dominant hyperthyroidism presenting with neuromuscular symptoms. The TSHr gene was investigated by direct sequencing. Functional properties of the mutant TSHr were investigated during transient expression in COS-7 cells. Family members were investigated by clinical and biochemical examinations. Sequence analysis revealed a previously reported heterozygous missense mutation Glycine 431 for Serine in the first transmembrane segment, leading to an increased specific constitutive activity. Three additional affected family members carried the same mutation. There was no indication of autoimmune disorder. All symptoms disappeared upon treatment with thacapzol and L-thyroxine and subsequent subtotal thyroidectomy. The data imply that neuromuscular symptoms can be caused by excessive thyroid hormone levels rather than by autoimmunity.

Hexosamine Biosynthetic Pathway Mutations Cause Neuromuscular Transmission Defect

PubMed Central

Senderek, Jan; Müller, Juliane S.; Dusl, Marina; Strom, Tim M.; Guergueltcheva, Velina; Diepolder, Irmgard; Laval, Steven H.; Maxwell, Susan; Cossins, Judy; Krause, Sabine; Muelas, Nuria; Vilchez, Juan J.; Colomer, Jaume; Mallebrera, Cecilia Jimenez; Nascimento, Andres; Nafissi, Shahriar; Kariminejad, Ariana; Nilipour, Yalda; Bozorgmehr, Bita; Najmabadi, Hossein; Rodolico, Carmelo; Sieb, Jörn P.; Steinlein, Ortrud K.; Schlotter, Beate; Schoser, Benedikt; Kirschner, Janbernd; Herrmann, Ralf; Voit, Thomas; Oldfors, Anders; Lindbergh, Christopher; Urtizberea, Andoni; von der Hagen, Maja; Hübner, Angela; Palace, Jacqueline; Bushby, Kate; Straub, Volker; Beeson, David; Abicht, Angela; Lochmüller, Hanns

2011-01-01

Neuromuscular junctions (NMJs) are synapses that transmit impulses from motor neurons to skeletal muscle fibers leading to muscle contraction. Study of hereditary disorders of neuromuscular transmission, termed congenital myasthenic syndromes (CMS), has helped elucidate fundamental processes influencing development and function of the nerve-muscle synapse. Using genetic linkage, we find 18 different biallelic mutations in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in 13 unrelated families with an autosomal recessive CMS. Consistent with these data, downregulation of the GFPT1 ortholog gfpt1 in zebrafish embryos altered muscle fiber morphology and impaired neuromuscular junction development. GFPT1 is the key enzyme of the hexosamine pathway yielding the amino sugar UDP-N-acetylglucosamine, an essential substrate for protein glycosylation. Our findings provide further impetus to study the glycobiology of NMJ and synapses in general. PMID:21310273

Effect of hypnotic suggestion on knee extensor neuromuscular properties in resting and fatigued states

PubMed Central

Antonini Philippe, Roberta; Guglielmo, Luiz Guilherme A.

2018-01-01

Purpose The aim of this study was to investigate whether hypnotic suggestions can alter knee extensor neuromuscular function at rest and during exercise. Methods Thirteen healthy volunteers (8 men and 5 women, 27 ± 3 years old) took part in this counterbalanced, crossover study including two experimental (hypnosis and control) sessions. Knee extensor neuromuscular function was tested before and after hypnosis suggestion by using a combination of voluntary contraction, transcutaneous femoral nerve electrical stimulation and transcranial magnetic stimulation (TMS). A fatiguing exercise (sustained submaximal contraction at 20% maximal voluntary contraction (MVC) force) was also performed to evaluate the potential influence of hypnosis on the extent and origin of neuromuscular adjustments. Results Hypnosis did not (p>0.05) alter MVC force or knee extensor neural properties. Corticospinal excitability, assessed with the amplitude of knee extensor motor evoked potentials, was also unchanged (p>0.05), as was the level of intracortical inhibition assessed with paired pulse TMS (short-interval intracortical inhibition, SICI). Time to task failure (~300 s) was not different (p>0.05) between the two sessions; accordingly, hypnosis did not influence neuromuscular adjustments measured during exercise and at task failure (p>0.05). Conclusion Hypnotic suggestions did not alter neuromuscular properties of the knee extensor muscles under resting condition or during/after exercise, suggesting that hypnosis-induced improvement in exercise performance and enhanced corticospinal excitability might be limited to highly susceptible participants. PMID:29684047

Ephedrine fails to accelerate the onset of neuromuscular block by vecuronium.

PubMed

Komatsu, Ryu; Nagata, Osamu; Ozaki, Makoto; Sessler, Daniel I

2003-08-01

The onset time of neuromuscular blocking drugs is partially determined by circulatory factors, including muscle blood flow and cardiac output. We thus tested the hypothesis that a bolus of ephedrine accelerates the onset of vecuronium neuromuscular block by increasing cardiac output. A prospective, randomized study was conducted in 53 patients scheduled for elective surgery. After the induction of anesthesia, the ulnar nerve was stimulated supramaximally every 10 s, and the evoked twitch response of the adductor pollicis was recorded with accelerometry. Patients were maintained under anesthesia with continuous infusion of propofol for 10 min and then randomly assigned to ephedrine 210 microg/kg (n = 27) or an equivalent volume of saline (n = 26). The test solution was given 1 min before the administration of 0.1 mg/kg of vecuronium. Cardiac output was monitored with impedance cardiography. Ephedrine, but not saline, increased cardiac index (17%; P = 0.003). Nonetheless, the onset of 90% neuromuscular block was virtually identical in the patients given ephedrine (183 +/- 41 s) and saline (181 +/- 47 s). There was no correlation between cardiac index and onset of the blockade. We conclude that the onset of the vecuronium-induced neuromuscular block is primarily determined by factors other than cardiac output. The combination of ephedrine and vecuronium thus cannot be substituted for rapid-acting nondepolarizing muscle relaxants. Ephedrine increased cardiac index but failed to speed onset of neuromuscular block with vecuronium. We conclude that ephedrine administration does not shorten the onset time of vecuronium.

Neuromuscular disease and respiratory physiology in children: putting lung function into perspective.

PubMed

Fauroux, Brigitte; Khirani, Sonia

2014-08-01

Neuromuscular diseases represent a heterogeneous group of disorders of the muscle, nerve or neuromuscular junction. The respiratory muscles are rarely spared in neuromuscular diseases even if the type of muscle involvement, severity and time course greatly varies among the different diseases. Diagnosis of respiratory muscle weakness is crucial because of the importance of respiratory morbidity and mortality. Presently, routine respiratory evaluation is based on non-invasive volitional tests, such as the measurement of lung volumes, spirometry and the maximal static pressures, which may be difficult or impossible to obtain in some young children. Other tools or parameters are thus needed to assess the respiratory muscle weakness and its consequences in young children. The measurement of oesogastric pressures can be helpful as they allow the diagnosis and quantification of paradoxical breathing, as well as the assessment of the strength of the inspiratory and expiratory muscles by means of the oesophageal pressure during a maximal sniff and of the gastric pressure during a maximal cough. Sleep assessment should also be part of the respiratory evaluation of children with neuromuscular disease with at least the recording of nocturnal gas exchange if polysomnography is not possible or unavailable. This improvement in the assessment of respiratory muscle performance may increase our understanding of the respiratory pathophysiology of the different neuromuscular diseases, improve patient care, and guide research and innovative therapies by identifying and validating respiratory parameters. © 2014 Asian Pacific Society of Respirology.

Short-chain chlorinated paraffins in soil, paddy seeds (Oryza sativa) and snails (Ampullariidae) in an e-waste dismantling area in China: Homologue group pattern, spatial distribution and risk assessment.

PubMed

Yuan, Bo; Fu, Jianjie; Wang, Yawei; Jiang, Guibin

2017-01-01

Short-chain chlorinated paraffins (SCCPs) in multi-environmental matrices are studied in Taizhou, Zhejiang Province, China, which is a notorious e-waste dismantling area. The investigated matrices consist of paddy field soil, paddy seeds (Oryza sativa, separated into hulls and rice unpolished) and apple snails (Ampullariidae, inhabiting the paddy fields). The sampling area covered a 65-km radius around the contamination center. C 10 and C 11 are the two predominant homologue groups in the area, accounting for about 35.7% and 33.0% of total SCCPs, respectively. SCCPs in snails and hulls are generally higher than in soil samples (30.4-530 ng/g dw), and SCCPs in hulls are approximate five times higher than in corresponding rice samples (4.90-55.1 ng/g dw). Homologue pattern analysis indicates that paddy seeds (both hull and rice) tend to accumulate relatively high volatile SCCP homologues, especially the ones with shorter carbon chain length, while snails tend to accumulate relatively high lipophilic homologues, especially the ones with more substituted chlorines. SCCPs in both paddy seeds and snails are linearly related to those in the soil. The e-waste dismantling area, which covers a radius of approximate 20 km, shows higher pollution levels for SCCPs according to their spatial distribution in four matrices. The preliminary assessment indicates that SCCP levels in local soils pose no significant ecological risk for soil dwelling organisms, but higher risks from dietary exposure of SCCPs are suspected for people living in e-waste dismantling area. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immediate effects of different treatments for the wrist joints of subdominant hands, using electromechanical reaction time.

PubMed

Hu, Chunying; Huang, Qiuchen; Yu, Lili; Zhou, Yue; Gu, Rui; Cui, Yao; Ge, Meng; Xu, Yanfeng; Liu, Jianfeng

2016-08-01

[Purpose] The aim of this study was to examine the immediate effects of muscle strength training and neuromuscular joint facilitation distal resistance training on wrist joints by using electromechanical reaction time. [Subjects and Methods] The subjects were 12 healthy young people (24.2 ± 3.1 years, 169.7 ± 6.5 cm, 65.3 ± 12.6 kg). Two kinds of isotonic contraction techniques were applied on the wrist joint: the wrist joint extension muscle strength training and the wrist joint extension pattern of neuromuscular joint facilitation. The electromechanical reaction time, premotor time, and motor time of the left upper limb were measured before and after each intervention session of muscle strength training and neuromuscular joint facilitation. [Results] The neuromuscular joint facilitation group showed significant shortening of the electromechanical reaction time and motor time after the intervention. [Conclusion] These results suggest that the electromechanical reaction time and motor time of the wrist joint can be improved by neuromuscular joint facilitation together with proximal resistance training, which can be used as a new form of exercise for improving the functions of subdominant hand wrist joints.

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

PubMed

Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

2013-12-01

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Computational model to investigate the relative contributions of different neuromuscular properties of tibialis anterior on force generated during ankle dorsiflexion.

PubMed

Siddiqi, Ariba; Poosapadi Arjunan, Sridhar; Kumar, Dinesh Kant

2018-01-16

This study describes a new model of the force generated by tibialis anterior muscle with three new features: single-fiber action potential, twitch force, and pennation angle. This model was used to investigate the relative effects and interaction of ten age-associated neuromuscular parameters. Regression analysis (significance level of 0.05) between the neuromuscular properties and corresponding simulated force produced at the footplate was performed. Standardized slope coefficients were computed to rank the effect of the parameters. The results show that reduction in the average firing rate is the reason for the sharp decline in the force and other factors, such as number of muscle fibers, specific force, pennation angle, and innervation ratio. The fast fiber ratio affects the simulated force through two significant interactions. This study has ranked the individual contributions of the neuromuscular factors to muscle strength decline of the TA and identified firing rate decline as the biggest cause followed by decrease in muscle fiber number and specific force. The strategy for strength preservation for the elderly should focus on improving firing rate. Graphical abstract Neuromuscular properties of Tibialis Anterior on force generated during ankle dorsiflexion.

Sugammadex as a reversal agent for neuromuscular block: an evidence-based review

PubMed Central

Schaller, Stefan Josef; Fink, Heidrun

2013-01-01

Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the “gold standard” muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing. PMID:24098155

The relationship between the target effective site concentration of rocuronium and the degree of recovery from neuromuscular blockade in elderly patients

PubMed Central

Fan, Xiaochong; Ma, Minyu; Li, Zhisong; Gong, Shengkai; Zhang, Wei; Wen, Yuanyuan

2015-01-01

Objective: To study the relationship between the target effective site concentration (Ce) of rocuronium and the degree of recovery from neuromuscular blockade in elderly patients. Methods: 50 elderly patients (ASA grade II) scheduled for selective surgical procedure under general anaesthesia were randomly divided into two groups, A and B, with 25 cases in each group. The Ce of rocuronium for intubation was 3 μg·ml-1 in both groups, and the Ce during operation were 0.8 and 1.0 μg·ml-1 in group A and B, respectively. When target controlled infusion of rocuronium was stopped, without the administration of reversal agents for neuromuscular blockade, the relationship between Ce and the first twitch height (T1) was studied by regression analysis. Results: There was a significant linear relationship between Ce and T1, and there was no statistical difference in regression coefficient and interception between group A and B (P>0.05). Conclusion: The degree of recovery from neuromuscular blockade could be judged by the target effective site concentration of rocuronium at the time of reversal from neuromuscular blockade in the elderly patients. PMID:26629159

[Neuromuscular deficits in chronic ankle instability. Frequency and significance - multicenter study].

PubMed

Schmidt, R; Becker, H P; Rauhut, F; Tannheimer, M

2014-08-01

The peroneal reaction time (PRT) is used in the assessment of neuromuscular deficits in chronic functional ankle instability. Powered by the Editorial Manager and Preprint Manager from Aries Systems Corporation the present study was conducted to determine the PRT in a large collective of patients with chronic ankle instability because it is unclear if this parameter of neuromuscular deficit is prolonged. In this study 186 patients underwent a diagnostic algorithm consisting of anamnesis, clinical examination, X-ray and determination of the PRT on a tilting platform. A prolonged PRT as a manifestation of a neuromuscular deficit could be detected in the majority of the patients (n = 143, 77%). Comparing the affected and healthy legs 77 patients (41%) showed a significant difference in talar shift (p = 0.002) and talar tilt (p = 0.04) in the radiological stress views. Of these 77 patients only 15 (8%) showed radiological evidence of a mechanical problem. As a consequence of recurring ankle sprains a post-traumatic deficit in proprioception has to be expected in most cases. In general a conservative therapy approach should be followed including specific training to improve neuromuscular and proprioceptive deficits.

Knee joint kinaesthesia and neuromuscular coordination during three phases of the menstrual cycle in moderately active women.

PubMed

Fridén, Cecilia; Hirschberg, Angelica Lindén; Saartok, Tönu; Renström, Per

2006-04-01

An increased incidence of sports related injuries in the premenstrual phase as well as in the menstrual phase of the menstrual cycle has been described. This may be explained by alterations in proprioception and neuromuscular coordination due to hormonal variations. Prospective, within women analysis of knee joint kinesthesia and neuromuscular coordination were performed by repeated measures analysis of variance in three hormonally verified phases of three consecutive menstrual cycles. Thirty-two healthy, moderately active female subjects volunteered to participate in the study. Twenty-five of the subjects performed at least one hormonally verified menstrual cycle. A specially designed device was used to investigate knee joint kinaesthesia and neuromuscular coordination was measured with the square hop test. These tests were carried out in the menstrual phase, ovulation phase and premenstrual phase determined by hormone analyses in three consecutive menstrual cycles. An impaired knee joint kinaesthesia was detected in the premenstrual phase and the performance of square hop test was significantly improved in the ovulation phase compared to the other two phases. The results of this study indicate that the variation of sex hormones in the menstrual cycle has an effect on performance of knee joint kinaesthesia and neuromuscular coordination.

Neuromuscular blocking properties of some bistropinium esters

PubMed Central

Haining, C. G.; Johnston, R. G.

1962-01-01

The neuromuscular blocking, anti-acetylcholine and ganglion blocking properties of two series of bistropinium esters were examined. The neuromuscular blocking activities of the mandelic acid esters of NN'-polymethylenebis(tropinium halides) were found to depend upon the number of carbon atoms (n) in the linking chain. Potency was enhanced more than 50 times as n was increased from 2 to 7. Compounds in which n equalled 7, 8, 9, 10 and 12 differed little in activity, but were generally more potent than tubocurarine in cats and rabbits. A peak of ganglion blocking action was obtained at the pentamethylene member. Esterification enhanced the feeble neuromuscular blocking properties of NN'-decamethylenebis(tropinium halide), the mandelic acid ester being more effective than the tropic, benzoic or phenylacetic acid esters in cats and rabbits. When two benzoic or mandelic acid esters of tropine were linked through their nitrogen atoms by a phenylenedimethyl grouping (-CH2.C6H4.CH2-), meta substitution was more effective than was ortho or para in producing neuromuscular block. The effectiveness of esterifying acids in m-phenylenedimethyl derivatives decreased in the following order, phenylacetic> tropic or mandelic>benzoic>acetic and diphenylacetic. PMID:13903721

Electrophysiological diagnosis and patterns of response to treatment of botulism with neuromuscular respiratory failure.

PubMed

Kongsaengdao, Subsai; Samintarapanya, Kanoksri; Rusmeechan, Siwarit; Sithinamsuwan, Pasiri; Tanprawate, Surat

2009-08-01

In this study we describe the electrophysiological findings in botulism patients with neuromuscular respiratory failure from major botulism outbreaks in Thailand. High-rate repetitive nerve stimulation testing (RNST) of the abductor digiti minimi (ADM) muscle of 17 botulism patients with neuromuscular respiratory failure showed mostly incremental responses, especially in response to >20-HZ stimulation. In the most severe stage of neuromuscular respiratory failure, RNST failed to elicit a compound muscle action potential (CMAP) of the ADM muscle. In the moderately severe stage, the initial CMAPs were of very low amplitude, and a 3-HZ RNST elicited incremental or decremental responses. A 10-HZ RNST elicited mainly decremental responses. In the early recovery stage, the initial CMAP amplitudes of the ADM muscle improved, with initially low amplitudes and an incremental response to 3- and 10-HZ RNSTs. Improved electrophysiological patterns of the ADM muscle correlated with improved respiratory muscle function. Incremental responses to 20-HZ RNST were most useful for diagnosis. The initial electrodiagnostic sign of recovery following treatment of neuromuscular respiratory failure was an increased CMAP amplitude and an incremental response to 10-20-HZ RNST. Muscle Nerve 40: 271-278, 2009.

Conservative management of neuromuscular scoliosis: personal experience and review of literature.

PubMed

Kotwicki, Tomasz; Jozwiak, Marek

2008-01-01

The principles of conservative management of neuromuscular scoliosis in childhood and adolescence are presented. Analysis of personal experience and literature review. The topic is discussed separately for patients with flaccid or spastic paresis. These demonstrate that conservative management might be proposed for patients with neuromuscular scoliosis in many clinical situations. In spastic disorders, it maintains the symmetry around the hip joints. Bracing is technically difficult and often is not tolerated well by cerebral palsy children. In patients with flaccid paresis, the fitting and the use of brace is easier than in spastic patients. The flexibility of the spinal curvature is more important. Functional benefits of conservative management of neuromuscular scoliosis comprise stable sitting, easier use of upper limbs, discharge of the abdomen from the collapsing trunk, increased diaphragm excursion, and, not always, prevention of curve progression. Specific natural history and multiple medical problems associated with the disease make the treatment of children with neuromuscular scoliosis an extremely complex issue, best addressed when a team approach is applied. Continuously improving techniques of conservative management, comprising bracing and physiotherapy, together with correctly timed surgery incorporated in the process of rehabilitation, provide the optimal care for patients.

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

PubMed

Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

2016-04-01

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

It's more than just physical therapy: reported utilization of physiotherapy services for adults with neuromuscular disorders attending a specialist centre.

PubMed

Hartley, Sandra; Stockley, Rachel

2013-02-01

The purpose of this study is to evaluate service users' perceptions of their utilization of the physiotherapy service at a specialist Neuromuscular Centre and to identify their reasons for and barriers to attending. A prospective survey design, consisting of a 13-item questionnaire was completed by 104 registered users of a physiotherapy service at a Neuromuscular Centre in northwest England. Descriptive statistics was employed to analyse data from Likert style questions and thematic analysis conducted on responses to open-ended questions. Over 79% of respondents were satisfied with the frequency and duration of their treatment. Respondents attended physiotherapy to obtain physical therapy, for general wellbeing and to access specialized resources. Barriers to attendance included work commitments, travel cost and time, and lack of Centre resources. Clients attending physiotherapy valued the specialist service including advice from therapists, perceived benefit from social interaction with other clients and physical therapy. Adults with neuromuscular disorders identified psychosocial as well as physical benefits from attending physiotherapy at the Neuromuscular Centre. The findings highlight the importance of service users' views in service provision and suggest that a collaborative commitment to patient management could by advantageous when developing physiotherapy services.

Teaching Visually Impaired Adults with a Neuromuscular Disorder.

ERIC Educational Resources Information Center

Williams, Susan

1983-01-01

The effects of four neuromuscular disorders (stroke, Parkinson's disease, Huntington's disease, and Lou Gehrig's disease) on concommitant visual impairments are considered. Rehabilitation approaches and equipment that help clients cope with the condition are described. (CL)

Unifying concept of serotonin transporter-associated currents.

PubMed

Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

2012-01-02

Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.

Unifying Concept of Serotonin Transporter-associated Currents*

PubMed Central

Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H.; Sandtner, Walter

2012-01-01

Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents. PMID:22072712

Distinct mechanisms determine organ left-right asymmetry patterning in an uncoupled way.

PubMed

Huang, Sizhou; Xu, Wenming; Su, Bingyin; Luo, Lingfei

2014-03-01

Disruption of Nodal in the lateral plate mesoderm (LPM) usually leads to left-right (LR) patterning defects in multiple organs. However, whether the LR patterning of organs is always regulated in a coupled way has largely not yet been elucidated. In addition, whether other crucial regulators exist in the LPM that coordinate with Nodal in regulating organ LR patterning is also undetermined. In this paper, after briefly summarizing the common process of LR patterning, the most puzzling question regarding the initiation of asymmetry is considered and the divergent mechanisms underlying the uncoupled LR patterning in different organs are discussed. On the basis of cases in which different organ LR patterning is determined in an uncoupled way via an independent mechanism or at a different time, we propose that there are other critical factors in the LPM that coordinate with Nodal to regulate heart LR asymmetry patterning during early LR patterning. © 2014 WILEY Periodicals, Inc.

Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria.

PubMed

Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Majerczak, Joanna; Zoladz, Jerzy A

2015-06-01

Mitochondrial respiratory and phosphorylation activities, mitochondrial uncoupling, and hydrogen peroxide formation were studied in isolated rat skeletal muscle mitochondria during experimentally induced hypothermia (25 °C) and hyperthermia (42 °C) compared to the physiological temperature of resting muscle (35 °C). For nonphosphorylating mitochondria, increasing the temperature from 25 to 42 °C led to a decrease in membrane potential, hydrogen peroxide production, and quinone reduction levels. For phosphorylating mitochondria, no temperature-dependent changes in these mitochondrial functions were observed. However, the efficiency of oxidative phosphorylation decreased, whereas the oxidation and phosphorylation rates and oxidative capacities of the mitochondria increased, with increasing assay temperature. An increase in proton leak, including uncoupling protein-mediated proton leak, was observed with increasing assay temperature, which could explain the reduced oxidative phosphorylation efficiency and reactive oxygen species production. Copyright © 2015 Elsevier Inc. All rights reserved.

Lipotoxicity, fatty acid uncoupling and mitochondrial carrier function.

PubMed

Rial, Eduardo; Rodríguez-Sánchez, Leonor; Gallardo-Vara, Eunate; Zaragoza, Pilar; Moyano, Eva; González-Barroso, M Mar

2010-01-01

Diseases like obesity, diabetes or generalized lipodystrophy cause a chronic elevation of circulating fatty acids that can become cytotoxic, a condition known as lipotoxicity. Fatty acids cause oxidative stress and alterations in mitochondrial structure and function. The uncoupling of the oxidative phosphorylation is one of the most recognized deleterious fatty acid effects and several metabolite transporters are known to mediate in their action. The fatty acid interaction with the carriers leads to membrane depolarization and/or the conversion of the carrier into a pore. The result is the opening of the permeability transition pore and the initiation of apoptosis. Unlike the other members of the mitochondrial carrier superfamily, the eutherian uncoupling protein UCP1 has evolved to achieve its heat-generating capacity in the physiological context provided by the brown adipocyte and therefore it is activated by the low fatty acid concentrations generated by the noradrenaline-stimulated lipolysis. Copyright © 2010 Elsevier B.V. All rights reserved.

The Stimulated Glycolytic Pathway Is Able to Maintain ATP Levels and Kinetic Patterns of Bovine Epididymal Sperm Subjected to Mitochondrial Uncoupling.

PubMed

Losano, João D A; Padín, Juan Fernando; Méndez-López, Iago; Angrimani, Daniel S R; García, Antonio G; Barnabe, Valquiria H; Nichi, Marcilio

2017-01-01

Studies have reported the importance of mitochondria in sperm functionality. However, for some species, the glycolytic pathway appears to be as important as oxidative phosphorylation in ATP synthesis and sperm kinetics. These mechanisms have not been fully elucidated for bovine spermatozoa. Therefore, the aim of this study was to evaluate the role of mitochondria and the glycolytic pathway in ATP synthesis, sperm movement patterns, and oxidative homeostasis of epididymal spermatozoa in bovine specimens. We observed that mitochondrial uncoupling with protonophores significantly reduced ATP levels. However, these levels were reestablished after stimulation of the glycolytic pathway. We verified the same pattern of results for sperm kinetic variables and the production of reactive oxygen species (ROS). Thus, we suggest that, after its appropriate stimulation, the glycolytic pathway is capable of maintaining ATP levels, sperm kinetic patterns, and oxidative balance of bovine epididymal spermatozoa submitted to mitochondrial uncoupling.

Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload.

PubMed

Pardo Andreu, G L; Inada, N M; Vercesi, A E; Curti, C

2009-01-01

One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- 4 to 130 +/- 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H+ leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.

Brown fat in a protoendothermic mammal fuels eutherian evolution.

PubMed

Oelkrug, Rebecca; Goetze, Nadja; Exner, Cornelia; Lee, Yang; Ganjam, Goutham K; Kutschke, Maria; Müller, Saskia; Stöhr, Sigrid; Tschöp, Matthias H; Crichton, Paul G; Heldmaier, Gerhard; Jastroch, Martin; Meyer, Carola W

2013-01-01

Endothermy has facilitated mammalian species radiation, but the sequence of events leading to sustained thermogenesis is debated in multiple evolutionary models. Here we study the Lesser hedgehog tenrec (Echinops telfairi), a phylogenetically ancient, 'protoendothermic' eutherian mammal, in which constantly high body temperatures are reported only during reproduction. Evidence for nonshivering thermogenesis is found in vivo during periodic ectothermic-endothermic transitions. Anatomical studies reveal large brown fat-like structures in the proximity of the reproductive organs, suggesting physiological significance for parental care. Biochemical analysis demonstrates high mitochondrial proton leak catalysed by an uncoupling protein 1 ortholog. Strikingly, bioenergetic profiling of tenrec uncoupling protein 1 reveals similar thermogenic potency as modern mouse uncoupling protein 1, despite the large phylogenetic distance. The discovery of functional brown adipose tissue in this 'protoendothermic' mammal links nonshivering thermogenesis directly to the roots of eutherian evolution, suggesting physiological importance prior to sustained body temperatures and migration to the cold.

Brown fat in a protoendothermic mammal fuels eutherian evolution

PubMed Central

Oelkrug, Rebecca; Goetze, Nadja; Exner, Cornelia; Lee, Yang; Ganjam, Goutham K.; Kutschke, Maria; Müller, Saskia; Stöhr, Sigrid; Tschöp, Matthias H.; Crichton, Paul G.; Heldmaier, Gerhard; Jastroch, Martin; Meyer, Carola W.

2013-01-01

Endothermy has facilitated mammalian species radiation, but the sequence of events leading to sustained thermogenesis is debated in multiple evolutionary models. Here we study the Lesser hedgehog tenrec (Echinops telfairi), a phylogenetically ancient, ‘protoendothermic’ eutherian mammal, in which constantly high body temperatures are reported only during reproduction. Evidence for nonshivering thermogenesis is found in vivo during periodic ectothermic–endothermic transitions. Anatomical studies reveal large brown fat-like structures in the proximity of the reproductive organs, suggesting physiological significance for parental care. Biochemical analysis demonstrates high mitochondrial proton leak catalysed by an uncoupling protein 1 ortholog. Strikingly, bioenergetic profiling of tenrec uncoupling protein 1 reveals similar thermogenic potency as modern mouse uncoupling protein 1, despite the large phylogenetic distance. The discovery of functional brown adipose tissue in this ‘protoendothermic’ mammal links nonshivering thermogenesis directly to the roots of eutherian evolution, suggesting physiological importance prior to sustained body temperatures and migration to the cold. PMID:23860571

Structural Sensitivity of a Prokaryotic Pentameric Ligand-gated Ion Channel to Its Membrane Environment*

PubMed Central

Labriola, Jonathan M.; Pandhare, Akash; Jansen, Michaela; Blanton, Michael P.; Corringer, Pierre-Jean; Baenziger, John E.

2013-01-01

Although the activity of the nicotinic acetylcholine receptor (nAChR) is exquisitely sensitive to its membrane environment, the underlying mechanisms remain poorly defined. The homologous prokaryotic pentameric ligand-gated ion channel, Gloebacter ligand-gated ion channel (GLIC), represents an excellent model for probing the molecular basis of nAChR sensitivity because of its high structural homology, relative ease of expression, and amenability to crystallographic analysis. We show here that membrane-reconstituted GLIC exhibits structural and biophysical properties similar to those of the membrane-reconstituted nAChR, although GLIC is substantially more thermally stable. GLIC, however, does not possess the same exquisite lipid sensitivity. In particular, GLIC does not exhibit the same propensity to adopt an uncoupled conformation where agonist binding is uncoupled from channel gating. Structural comparisons provide insight into the chemical features that may predispose the nAChR to the formation of an uncoupled state. PMID:23463505

Uncoupling of reading and IQ over time: empirical evidence for a definition of dyslexia.

PubMed

Ferrer, Emilio; Shaywitz, Bennett A; Holahan, John M; Marchione, Karen; Shaywitz, Sally E

2010-01-01

Developmental dyslexia is defined as an unexpected difficulty in reading in individuals who otherwise possess the intelligence and motivation considered necessary for fluent reading, and who also have had reasonable reading instruction. Identifying factors associated with normative and impaired reading development has implications for diagnosis, intervention, and prevention. We show that in typical readers, reading and IQ development are dynamically linked over time. Such mutual interrelationships are not perceptible in dyslexic readers, which suggests that reading and cognition develop more independently in these individuals. To our knowledge, these findings provide the first empirical demonstration of a coupling between cognition and reading in typical readers and a developmental uncoupling between cognition and reading in dyslexic readers. This uncoupling was the core concept of the initial description of dyslexia and remains the focus of the current definitional model of this learning disability.

Classical-processing and quantum-processing signal separation methods for qubit uncoupling

NASA Astrophysics Data System (ADS)

Deville, Yannick; Deville, Alain

2012-12-01

The Blind Source Separation problem consists in estimating a set of unknown source signals from their measured combinations. It was only investigated in a non-quantum framework up to now. We propose its first quantum extensions. We thus introduce the Quantum Source Separation field, investigating both its blind and non-blind configurations. More precisely, we show how to retrieve individual quantum bits (qubits) only from the global state resulting from their undesired coupling. We consider cylindrical-symmetry Heisenberg coupling, which e.g. occurs when two electron spins interact through exchange. We first propose several qubit uncoupling methods which typically measure repeatedly the coupled quantum states resulting from individual qubits preparations, and which then statistically process the classical data provided by these measurements. Numerical tests prove the effectiveness of these methods. We then derive a combination of quantum gates for performing qubit uncoupling, thus avoiding repeated qubit preparations and irreversible measurements.

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome

PubMed Central

Macario, Alex; Chow, John L; Dexter, Franklin

2006-01-01

Background Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? Methods The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. Results Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5% – 95% percentiles $42,259 – $83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. Conclusion ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS. PMID:16539706

Neuromuscular electrical stimulation improves exercise tolerance in patients with advanced heart failure on continuous intravenous inotropic support use-randomized controlled trial.

PubMed

Forestieri, Patrícia; Bolzan, Douglas W; Santos, Vinícius B; Moreira, Rita Simone Lopes; de Almeida, Dirceu Rodrigues; Trimer, Renata; de Souza Brito, Flávio; Borghi-Silva, Audrey; de Camargo Carvalho, Antonio Carlos; Arena, Ross; Gomes, Walter J; Guizilini, Solange

2018-01-01

To evaluate the impact of a short-term neuromuscular electrical stimulation program on exercise tolerance in hospitalized patients with advanced heart failure who have suffered an acute decompensation and are under continuous intravenous inotropic support. A randomized controlled study. Initially, 195 patients hospitalized for decompensated heart failure were recruited, but 70 were randomized. Patients were randomized into two groups: control group subject to the usual care ( n = 35); neuromuscular electrical stimulation group ( n = 35) received daily training sessions to both lower extremities for around two weeks. The baseline 6-minute walk test to determine functional capacity was performed 24 hours after hospital admission, and intravenous inotropic support dose was daily checked in all patients. The outcomes were measured in two weeks or at the discharge if the patients were sent back home earlier than two weeks. After losses of follow-up, a total of 49 patients were included and considered for final analysis (control group, n = 25 and neuromuscular electrical stimulation group, n = 24). The neuromuscular electrical stimulation group presented with a higher 6-minute walk test distance compared to the control group after the study protocol (293 ± 34.78 m vs. 265.8 ± 48.53 m, P < 0.001, respectively). Neuromuscular electrical stimulation group also demonstrated a significantly higher dose reduction of dobutamine compared to control group after the study protocol (2.72 ± 1.72 µg/kg/min vs. 3.86 ± 1.61 µg/kg/min, P = 0.001, respectively). A short-term inpatient neuromuscular electrical stimulation rehabilitation protocol improved exercise tolerance and reduced intravenous inotropic support necessity in patients with advanced heart failure suffering a decompensation episode.

Neuromuscular blocking agent administration for emergent tracheal intubation is associated with decreased prevalence of procedure-related complications.

PubMed

Wilcox, Susan R; Bittner, Edward A; Elmer, Jonathan; Seigel, Todd A; Nguyen, Nicole Thuy P; Dhillon, Anahat; Eikermann, Matthias; Schmidt, Ulrich

2012-06-01

Emergent intubation is associated with a high rate of complications. Neuromuscular blocking agents are routinely used in the operating room and emergency department to facilitate intubation. However, use of neuromuscular blocking agents during emergent airway management outside of the operating room and emergency department is controversial. We hypothesized that the use of neuromuscular blocking agents is associated with a decreased prevalence of hypoxemia and reduced rate of procedure-related complications. Five hundred sixty-six patients undergoing emergent intubations in two tertiary care centers, Massachusetts General Hospital, Boston, MA, and the University of California Los Angeles, Ronald Reagan Medical Center, Los Angeles, CA, were enrolled in a prospective, observational study. The 112 patients intubated during cardiopulmonary resuscitation were excluded, leaving 454 patients for analysis. All intubations were supervised by attendings trained in Critical Care Medicine. We measured intubating conditions, oxygen saturation during and 5 mins following intubation. We assessed the prevalence of procedure-related complications defined as esophageal intubation, traumatic intubation, aspiration, dental injury, and endobronchial intubation. The use of neuromuscular blocking agents was associated with a lower prevalence of hypoxemia (10.1% vs. 17.4%, p = .022) and a lower prevalence of procedure-related complications (3.1% vs. 8.3%, p = .012). This association persisted in a multivariate analysis, which controlled for airway grade, sedation, and institution. Use of neuromuscular blocking agents was associated with significantly improved intubating conditions (laryngeal view, p = .014; number of intubation attempts, p = .049). After controlling for the number of intubation attempts and laryngoscopic view, muscle relaxant use is an independent predictor of complications associated with emergency intubation (p = .037), and there is a trend towards improvement of oxygenation (p = .07). The use of neuromuscular blocking agents, when used by intensivists with a high level of training and experience, is associated with a decrease in procedure-related complications.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis

PubMed Central

Patten, Shunmoogum A.; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary A.B.; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J. Alexander

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease. PMID:29202456

[Neuromuscular blocking and respiratory depressing actions of sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate].

PubMed

Cao, B J; Chen, Z K; Chi, Z Q

1990-05-01

The neuromuscular blocking and respiratory depressing actions of the new insecticide sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate (SCD) were investigated. In peroneal-tibialis anterior nerve-muscle preparations of urethane anesthetized rabbit, SCD 6.5 mg/kg iv completely depressed the indirectly elicited twitch tension but not the directly elicited one. This compound also caused initial potentiation of the indirectly elicited twitch tension. In the partially paralyzed preparations, potentiation of contractions occurred following a brief period of indirectly tetanic stimulation. Nereistoxin but not SCD blocked the indirectly elicited twitch tension of isolated rat diaphragm. The neuromuscular blockade induced by SCD and nereistoxin was antagonized by neostigmine and 4-aminopyridine. SCD and nereistoxin had little or no effect on arterial blood pressure and phrenic nerve discharge of rabbits. The results indicated that SCD-poisoned rabbits died of respiratory paralysis following the neuromuscular blockade.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

PubMed

Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

Transmitter release in the neuromuscular synapse of the protein kinase C theta-deficient adult mouse.

PubMed

Besalduch, Núria; Santafé, Manel M; Garcia, Neus; Gonzalez, Carmen; Tomás, Marta; Tomás, Josep; Lanuza, Maria A

2011-04-01

We studied structural and functional features of the neuromuscular junction in adult mice (P30) genetically deficient in the protein kinase C (PKC) theta isoform. Confocal and electron microscopy shows that there are no differences in the general morphology of the endplates between PKC theta-deficient and wild-type (WT) mice. Specifically, there is no difference in the density of the synaptic vesicles. However, the myelin sheath is not as thick in the intramuscular nerve fibers of the PKC theta-deficient mice. We found a significant reduction in the size of evoked endplate potentials and in the frequency of spontaneous, asynchronous, miniature endplate potentials in the PKC theta-deficient neuromuscular preparations in comparison with the WT, but the mean amplitude of the spontaneous potentials is not different. These changes indicate that PKC theta has a presynaptic role in the function of adult neuromuscular synapses. Copyright © 2010 Wiley-Liss, Inc.

Neuromuscular orthotics in the treatment of craniomandibular dysfunction and the effects on patients with multiple sclerosis: a pilot study.

PubMed

Heit, Tammarie

2011-01-01

The purpose of this pilot study was to identify, measure and document an effect on the subjective multiple sclerosis symptoms and compare it to any objective data changes in the neuromuscular system of the head and neck, following the correction of the jaw position using a neuromuscular orthotic. The hope is to provide clinical evidence of improvement in the disease long-term without relying on the subjective evidence of remissions and exacerbations reported by the patient. The evidence found in the current pilot study measured improvement of head position, jaw position, jaw function, and airway in the neuromuscular bite position, which correlated with the improvement of subjective symptoms of craniomandibular dysfunction and multiple sclerosis. Studies show that the bite affects blood flow in the brain, which may explain the improvement of the patients in the current study.

[Prolonged neuromuscular block in a patient with butyrylcholinesterase deficiency].

PubMed

Mabboux, I; Hary, B; Courcelle, S; Ceppa, F; Delacour, H

2016-05-01

Succinylcholine is a neuromuscular block whose duration of action depends on rapid hydrolysis by butyrylcholinesterase (BChE). In patients with common BChE activities, succinylcholine duration of action is short (10min). BChE deficiency induces a slower hydrolysis of the drug and consequently prolonged neuromuscular block, leading to apnea. We report a case of prolonged neuromuscular block after administration of succinylcholine in a 14-year-old boy. Biological investigations revealed a marked BChE deficiency (1099U/L) related to the presence of three point mutations in the BCHE gene in a compound heterozygous state: p.Asp70Gly (rs1799807), p.Ala539Tyr (rs1803274), and p.Phe118Valfs*12 (rs398124632). The diagnosis of genetic BChE deficiency (OMIM 177400) was retained. This case is intended to present the pathophysiology of genetic BChE deficiency, its management, and the diagnostic strategy to be implemented. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Verification of Dismantlement of Nuclear Warheads and Controls on Nuclear Materials

DTIC Science & Technology

1993-01-12

754001- 40-SS00 Staclaed Form 296 (Rov. 2.-9) Pwww-esu o s IS ŖS-wa Contents EXECUTIVE SUMMARY 1 1 INTRODUCTION 7 1.1 Study Charge ...for monitoring both non-proliferation and dismantlement. 6 1 INTRODUCTION 1.1 Study Charge This study addresses the question of monitorin6 future...Co59 + n 19 barn 5 yr 7 Ni59 NijM + n 4.4 barn 10s yr e- capture Ni63 Ni62 + n 15 barn 92 yr p 32 p 3l + n 0.19 barn 14 day f- S 3 5 SM + n 0.27 barn

KENNEDY SPACE CENTER, FLA. - On Launch Complex 17-B, Cape Canaveral Air Force Station, the Space Infrared Telescope Facility (SIRTF) observatory is being dismantled from atop the Delta II rocket. It will be taken back to NASA Spacecraft Hangar AE. SIRTF will remain in the clean room at Hangar AE until it returns to the pad in early August.

NASA Image and Video Library

2003-05-02

KENNEDY SPACE CENTER, FLA. - On Launch Complex 17-B, Cape Canaveral Air Force Station, the Space Infrared Telescope Facility (SIRTF) observatory is being dismantled from atop the Delta II rocket. It will be taken back to NASA Spacecraft Hangar AE. SIRTF will remain in the clean room at Hangar AE until it returns to the pad in early August.

KENNEDY SPACE CENTER, FLA. - Workers on Launch Complex 17-B, Cape Canaveral Air Force Station, start dismantling the Space Infrared Telescope Facility (SIRTF) observatory from atop the Delta II rocket. It will be taken back to NASA Spacecraft Hangar AE. SIRTF will remain in the clean room at Hangar AE until it returns to the pad in early August.

NASA Image and Video Library

2003-05-02

KENNEDY SPACE CENTER, FLA. - Workers on Launch Complex 17-B, Cape Canaveral Air Force Station, start dismantling the Space Infrared Telescope Facility (SIRTF) observatory from atop the Delta II rocket. It will be taken back to NASA Spacecraft Hangar AE. SIRTF will remain in the clean room at Hangar AE until it returns to the pad in early August.

Development and destruction of the first state funded anti-smoking campaign in the USA.

PubMed

Tsoukalas, T H; Glantz, S A

2003-06-01

Minnesota was the first state in the USA to implement a large state funded tobacco control programme (in 1985). Despite evidence of effectiveness, it was dismantled in 1993. To describe and analyse how and why these events transpired and identify lessons for tobacco control advocates facing similar challenges in the 21st century. Case study based on previously secret tobacco industry documents, news reports, research reports, official documents, and interviews with health advocates and state government officials. Unable to defeat funding for this campaign in 1985, the tobacco industry organised groups which eliminated it later. Despite the programme's documented effectiveness, it was dismantled based on claims of fiscal crisis. These claims were not true; the real debate was what to do with the state's surplus. Health advocates failed to challenge the claim of fiscal crisis or mobilise public support for the programme. Simply quoting evidence that a tobacco control programme is effective does not ensure its continuing survival. Claims of fiscal crisis are an effective cover for tobacco industry efforts to dismantle successful programmes, particularly if health advocates accept these claims and fail to mobilise political pressure to defend the programme.

Development and destruction of the first state funded anti-smoking campaign in the USA

PubMed Central

Tsoukalas, T; Glantz, S

2003-01-01

Background: Minnesota was the first state in the USA to implement a large state funded tobacco control programme (in 1985). Despite evidence of effectiveness, it was dismantled in 1993. Objective: To describe and analyse how and why these events transpired and identify lessons for tobacco control advocates facing similar challenges in the 21st century. Design: Case study based on previously secret tobacco industry documents, news reports, research reports, official documents, and interviews with health advocates and state government officials. Results: Unable to defeat funding for this campaign in 1985, the tobacco industry organised groups which eliminated it later. Despite the programme's documented effectiveness, it was dismantled based on claims of fiscal crisis. These claims were not true; the real debate was what to do with the state's surplus. Health advocates failed to challenge the claim of fiscal crisis or mobilise public support for the programme. Conclusions: Simply quoting evidence that a tobacco control programme is effective does not ensure its continuing survival. Claims of fiscal crisis are an effective cover for tobacco industry efforts to dismantle successful programmes, particularly if health advocates accept these claims and fail to mobilise political pressure to defend the programme. PMID:12773734

Radiochemistry Lab Decommissioning and Dismantlement. AECL, Chalk River Labs, Ontario, Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenny, Stephen

2008-01-15

Atomic Energy of Canada (AECL) was originally founded in the mid 1940's to perform research in radiation and nuclear areas under the Canadian Defense Department. In the mid 50's The Canadian government embarked on several research and development programs for the development of the Candu Reactor. AECL was initially built as a temporary site and is now faced with many redundant buildings. Prior to 2004 small amounts of Decommissioning work was in progress. Many reasons for deferring decommissioning activities were used with the predominant ones being: 1. Reduction in radiation doses to workers during the final dismantlement, 2. Development ofmore » a long-term solution for the management of radioactive wastes in Canada, 3. Financial constraints presented by the number of facilities shutdown that would require decommissioning funds and the absence of an approved funding strategy. This has led to the development of a comprehensive decommissioning plan that is all inclusive of AECL's current and legacy liabilities. Canada does not have a long-term disposal site; therefore waste minimization becomes the driving factor behind decontamination for decommissioning before and during dismantlement. This decommissioning job was a great learning experience for decommissioning and the associated contractors who worked on this project. Throughout the life of the project there was a constant focus on waste minimization. This focus was constantly in conflict with regulatory compliance primarily with respect to fire regulations and protecting the facility along with adjacent facilities during the decommissioning activities. Discrepancies in historical documents forced the project to treat every space as a contaminated space until proven differently. Decommissioning and dismantlement within an operating site adds to the complexity of the tasks especially when it is being conducted in the heart of the plant. This project was very successful with no lost time accidents in over one hundred thousand hours worked, on schedule and under budget despite some significant changes throughout the decommissioning phases. The actual cost to decommission this building will come in under 9 million dollars vs. an estimated 14.5 million dollars. This paper will cover some of the unique aspects of dismantling a radioactive building that has seen pretty much every element of the periodic table pass through it with the client requirement focused on minimization of radioactive waste volumes.« less

S-nitrosoglutathione reductase deficiency-induced S-nitrosylation results in neuromuscular dysfunction.

PubMed

Montagna, Costanza; Di Giacomo, Giuseppina; Rizza, Salvatore; Cardaci, Simone; Ferraro, Elisabetta; Grumati, Paolo; De Zio, Daniela; Maiani, Emiliano; Muscoli, Carolina; Lauro, Filomena; Ilari, Sara; Bernardini, Sergio; Cannata, Stefano; Gargioli, Cesare; Ciriolo, Maria R; Cecconi, Francesco; Bonaldo, Paolo; Filomeni, Giuseppe

2014-08-01

Nitric oxide (NO) production is implicated in muscle contraction, growth and atrophy, and in the onset of neuropathy. However, many aspects of the mechanism of action of NO are not yet clarified, mainly regarding its role in muscle wasting. Notably, whether NO production-associated neuromuscular atrophy depends on tyrosine nitration or S-nitrosothiols (SNOs) formation is still a matter of debate. Here, we aim at assessing this issue by characterizing the neuromuscular phenotype of S-nitrosoglutathione reductase-null (GSNOR-KO) mice that maintain the capability to produce NO, but are unable to reduce SNOs. We demonstrate that, without any sign of protein nitration, young GSNOR-KO mice show neuromuscular atrophy due to loss of muscle mass, reduced fiber size, and neuropathic behavior. In particular, GSNOR-KO mice show a significant decrease in nerve axon number, with the myelin sheath appearing disorganized and reduced, leading to a dramatic development of a neuropathic phenotype. Mitochondria appear fragmented and depolarized in GSNOR-KO myofibers and myotubes, conditions that are reverted by N-acetylcysteine treatment. Nevertheless, although atrogene transcription is induced, and bulk autophagy activated, no removal of damaged mitochondria is observed. These events, alongside basal increase of apoptotic markers, contribute to persistence of a neuropathic and myopathic state. Our study provides the first evidence that GSNOR deficiency, which affects exclusively SNOs reduction without altering nitrotyrosine levels, results in a clinically relevant neuromuscular phenotype. These findings provide novel insights into the involvement of GSNOR and S-nitrosylation in neuromuscular atrophy and neuropathic pain that are associated with pathological states; for example, diabetes and cancer.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study.

PubMed

Duyff, R F; Van den Bosch, J; Laman, D M; van Loon, B J; Linssen, W H

2000-06-01

To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism. A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment. In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6 months). Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

Functional capacity and muscular abnormalities in subclinical hypothyroidism.

PubMed

Reuters, Vaneska S; Teixeira, Patrícia de Fátima S; Vigário, Patrícia S; Almeida, Cloyra P; Buescu, Alexandre; Ferreira, Márcia M; de Castro, Carmen L N; Gold, Jaime; Vaisman, Mario

2009-10-01

Neuromuscular abnormalities and low exercise tolerance are frequently observed in overt hypothyroidism, but it remains controversial if they can also occur in subclinical hypothyroidism (sHT). The aim of this study is to evaluate neuromuscular symptoms, muscle strength, and exercise capacity in sHT, compared with healthy euthyroid individuals. A cross-sectional study was performed with 44 sHT and 24 euthyroid outpatients from a university hospital. Neuromuscular symptoms were questioned. Muscle strength was tested for neck, shoulder, arm, and hip muscle groups, using manual muscle testing (MMT). Quadriceps muscle strength was tested with a chair dynamometer and inspiratory muscle strength (IS) by a manuvacuometer. Functional capacity was estimated based on the peak of oxygen uptake (mL/kg/min), using the Bruce treadmill protocol. Cramps (54.8% versus 25.0%; P < 0.05), weakness (45.2% versus 12.6; P < 0.05), myalgia (47.6% versus 25.0%; P = 0.07), and altered MMT (30.8% versus 8.3%; P = 0.040) were more frequent in sHT. Quadriceps strength and IS were not impaired in sHT and the same was observed for functional capacity. IS was significantly lower in patients complaining of fatigue and weakness (P < 0.05) and tended to be lower in those with altered MMT (P = 0.090). Neuromuscular complaints and altered MMT were significantly more frequent in sHT than in controls, and IS was lower in patients with these abnormalities. Results suggest that altered muscle strength by MMT and the coexistence of neuromuscular complaints in patients with sHT may indicate neuromuscular dysfunction.

Interaction of antibiotics on pipecuronium-induced neuromuscular blockade.

PubMed

de Gouw, N E; Crul, J F; Vandermeersch, E; Mulier, J P; van Egmond, J; Van Aken, H

1993-01-01

To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). Prospective, randomized, placebo-controlled study. Inpatient gynecologic and gastroenterologic service at a university medical center. Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo. The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.

Effects of Neuromuscular Training on Children and Young Adults with Down Syndrome: Systematic Review and Meta-Analysis.

PubMed

Sugimoto, Dai; Bowen, Samantha L; Meehan, William P; Stracciolini, Andrea

2016-08-01

To synthesize existing research evidence and examine effects of neuromuscular training on general strength, maximal strength, and functional mobility tasks in children and young adults with Down syndrome. PubMed and EBSCO were used as a data source. To attain the aim of this study, literature search was performed under following inclusion criteria: (1) included participants with Down syndrome, (2) implemented a neuromuscular training intervention and measured outcome variables of general strength, maximal strength, and functional mobility tasks, (3) had a group of participants whose mean ages were under 30 years old, (4) employed a prospective controlled design, and (5) used mean and standard deviations to express the outcome variables. Effect size was calculated from each study based on pre- and post-testing value differences in general strength, maximal strength, and functional mobility tasks between control and intervention groups. The effect size was further classified in to one of the following categories: small, moderate, and large effects. Seven studies met inclusion criteria. Analysis indicated large to moderate effects on general strength, moderate to small effects on maximal strength, and small effect on functional mobility tasks by neuromuscular training. Although there were limited studies, the results showed that neuromuscular training could be used as an effective intervention in children and young adults with Down syndrome. Synthesis of seven reviewed studies indicated that neuromuscular training could be beneficial to optimize general and maximal muscular strength development in children and young adults with Down syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stunted PFC activity during neuromuscular control under stress with obesity.

PubMed

Mehta, Ranjana K

2016-02-01

Obesity is an established risk factor for impaired cognition, which is primarily regulated by the prefrontal cortex (PFC). However, very little is known about the neural pathways that underlie obesity-related declines in neuromuscular control, particularly under stress. The purpose of this study was to determine the role of the PFC on neuromuscular control during handgrip exertions under stress with obesity. Twenty non-obese and obese young adults performed submaximal handgrip exertions in the absence and presence of a concurrent stressful task. Primary dependent measures included oxygenated hemoglobin (HbO2: a measure of PFC activity) and force fluctuations (an indicator of neuromuscular control). Higher HbO2 levels in the PFC were observed in the non-obese compared to the obese group (P = 0.009). In addition, higher HbO2 levels were observed in the stress compared to the control condition in the non-obese group; however, this trend was reversed in the obese group (P = 0.043). In general, force fluctuations increased by 26% in the stress when compared to the control condition (P = 0.001) and obesity was associated with 39% greater force fluctuation (P = 0.024). Finally, while not significant, obesity-related decrements in force fluctuations were magnified under stress (P = 0.063). The current study provides the first evidence that neuromuscular decrements with obesity were associated with impaired PFC activity and this relationship was augmented in stress conditions. These findings are important because they provide new information on obesity-specific changes in brain function associated with neuromuscular control since the knowledge previously focused largely on obesity-specific changes in peripheral muscle capacity.

Effects of mirror therapy combined with neuromuscular electrical stimulation on motor recovery of lower limbs and walking ability of patients with stroke: a randomized controlled study.

PubMed

Xu, Qun; Guo, Feng; Salem, Hassan M Abo; Chen, Hong; Huang, Xiaolin

2017-12-01

To investigate the effectiveness of mirror therapy combined with neuromuscular electrical stimulation in promoting motor recovery of the lower limbs and walking ability in patients suffering from foot drop after stroke. Randomized controlled study. Inpatient rehabilitation center of a teaching hospital. Sixty-nine patients with foot drop. Patients were randomly divided into three groups: control, mirror therapy, and mirror therapy + neuromuscular electrical stimulation. All groups received interventions for 0.5 hours/day and five days/week for four weeks. 10-Meter walk test, Brunnstrom stage of motor recovery of the lower limbs, Modified Ashworth Scale score of plantar flexor spasticity, and passive ankle joint dorsiflexion range of motion were assessed before and after the four-week period. After four weeks of intervention, Brunnstrom stage ( P = 0.04), 10-meter walk test ( P < 0.05), and passive range of motion ( P < 0.05) showed obvious improvements between patients in the mirror therapy and control groups. Patients in the mirror therapy + neuromuscular electrical stimulation group showed better results than those in the mirror therapy group in the 10-meter walk test ( P < 0.05). There was no significant difference in spasticity between patients in the two intervention groups. However, compared with patients in the control group, patients in the mirror therapy + neuromuscular electrical stimulation group showed a significant decrease in spasticity ( P < 0.001). Therapy combining mirror therapy and neuromuscular electrical stimulation may help improve walking ability and reduce spasticity in stroke patients with foot drop.

Is time to peak effect of neuromuscular blocking agents dependent on dose? Testing the concept of buffered diffusion.

PubMed

Proost, J H; Houwertjes, M C; Wierda, J M K H

2008-07-01

For neuromuscular blocking agents, an inverse relationship between potency and time to peak effect has been observed. To test the hypothesis that this relationship is due to buffered diffusion, we investigated the influence of dose on time to peak effect. Pharmacokinetic-pharmacodynamic simulations were performed to support the expected relationships between potency, dose, peak effect and time to peak effect. Pigs (20-28 kg body weight) were anaesthetized with ketamine and midazolam, followed by pentobarbital and fentanyl intravenously. Neuromuscular block was measured by stimulating the peroneal nerve supramaximally at 0.1 Hz and measuring the response of the tibialis anterior muscle mechanomyographically. After an initial dose to establish the individual ED90 of a neuromuscular blocking agent (rocuronium, vecuronium, pipecuronium or d-tubocurarine), five different doses of the same compound were administered to each animal, aiming at 20%, 40%, 60%, 75% or 90% block, in a random order. Doses were given 45 min after complete recovery of the twitch response. For rocuronium and pipecuronium, time to peak effect increased with dose, whereas dose did not affect time to peak effect of vecuronium and d-tubocurarine. Simulations predict that time to peak effect decreases with dose if buffered diffusion is taken into account. The results suggest that buffered diffusion does not play a dominant role in the time to peak effect of neuromuscular blocking agents. Therefore it is unlikely that the observed inverse relationship between potency and time to peak effect of neuromuscular blocking agents in the clinical range is due to buffered diffusion.

Involvement of oxygen free radicals in the respiratory uncoupling induced by free calcium and ADP-magnesium in isolated cardiac mitochondria: comparing reoxygenation in cultured cardiomyocytes.

PubMed

Meynier, Alexandra; Razik, Hafida; Cordelet, Catherine; Grégoire, Stéphane; Demaison, Luc

2003-01-01

Recently, we have observed that the simultaneous application of free calcium (fCa) and ADP-magnesium (Mg) reduced the ADP:O ratio in isolated cardiac mitochondria. The uncoupling was prevented by cyclosporin A, an inhibitor of the permeability transition pore. The purpose of this study was to know if the generation of oxygen free radicals (OFR) is involved in this phenomenon and if it occurs during reoxygenation (Reox) of cultured cardiomyocytes. Cardiac mitochondria were harvested from male Wistar rats. Respiration was assessed in two media with different fCa concentrations (0 or 0.6 microM) with palmitoylcarnitine and ADP-Mg as respiration substrates. The production of Krebs cycle intermediates (KCI) was determined. Without fCa in the medium, the mitochondria displayed a large production of citrate + isocitrate + alpha-ketoglutarate. fCa drastically reduced these KCI and promoted the accumulation of succinate. To know if OFR are involved in the respiratory uncoupling, the effect of 4OH-TEMPO (250 microM), a hydrosoluble scavenger of OFR, was tested. 4OH-TEMPO completely abolished the fCa- and ADP-Mg-induced uncoupling. Conversely, vitamin E contributed to further decreasing the ADP:O ratio. Since no hydrosoluble electron acceptor was added in our experiment, the oxygen free radical-induced oxidized vitamin E was confined near the mitochondrial membranes, which should reduce the ADP:O ratio by opening the permeability transition pore. The generation of OFR could result from the matrix accumulation of succinate. Taken together, these results indicate that mitochondrial Ca uptake induces a slight increase in membrane permeability. Thereafter, Mg enters the matrix and, in combination with Ca, stimulates the isocitrate and/or alpha-ketoglutarate dehydrogenases. Matrix succinate favors oxygen free radical generation that further increases membrane permeability and allows respiratory uncoupling through proton leakage. To determine whether the phenomenon takes place during Reox, cultured cardiomyocytes were subjected to hypoxia and Reox. 14C-palmitate was added during Reox to determine the KCI profile. Succinate had not increased during Reox. In conclusion, calcium- and ADP-Mg-induced respiratory uncoupling is due to oxygen free radical generation through excess matrix accumulation of succinate. The phenomenon does not occur during reoxygenation because of a total restoration of mitochondrial magnesium and/or ADP concentration.

British Thoracic Society guideline for respiratory management of children with neuromuscular weakness: commentary.

PubMed

Hull, Jeremy

2012-07-01

The British Thoracic Society guideline for respiratory management of children with neuromuscular weakness summarises the available evidence in this field and provides recommendations that will aid healthcare professionals in delivering good quality patient care.

The use of an online support group for neuromuscular disorders: a thematic analysis of message postings.

PubMed

Meade, Oonagh; Buchanan, Heather; Coulson, Neil

2017-06-08

People affected by neuromuscular disorders can experience adverse psychosocial consequences and difficulties accessing information and support. Online support groups provide new opportunities for peer support. The aim of this study was to understand how contributors used the message board function of a newly available neuromuscular disorders online support group. Message postings (n = 1951) from the first five months of the message board of a newly formed online support group for neuromuscular disorders hosted by a charitable organization were analyzed using inductive thematic analysis. Members created a sense of community through disclosing personal information, connecting with people with similar illness experiences or interests, welcoming others and sharing aspirations for the development of a resourceful community. Experiences, emotional reactions and support were shared in relation to: delayed diagnosis; symptom interpretation; illness management and progression; the isolating impact of rare disorders; and the influence of social and political factors on illness experiences. This study provided a novel insight into individuals' experiences of accessing a newly available online support group for rare conditions hosted by a charitable organization. The findings highlight how the online support group provided an important peer support environment for members to connect with others, exchange information and support and engender discussion on political and social issues unique to living with often-rare neuromuscular disorders. Online support groups may therefore provide an important and easily accessible support outlet for people with neuromuscular disorders as well as a platform for empowering members to raise awareness about the impact of living with these conditions. Further research is needed to examine member motivations for using such groups and any effects of participation in greater detail. Implications for rehabilitation Online support groups may provide a unique forum for information sharing and peer support between people affected by often rare, neuromuscular conditions. Rehabilitation professionals may wish to signpost those affected by neuromuscular disorders to such groups. An advantage is that these groups are freely available and can be accessed from anywhere and at any time. Members may be able to learn about the diagnosis and symptom experiences of others, discuss coping strategies, validate illness experiences and discuss social and political issues relating to living with these conditions. Further research is needed before researchers and clinicians can fully understand participants' motivations for, and experiences of, using such groups and any potential psychosocial benefits.

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-02-01

Among all the drugs used for general anaesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anaesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anaesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anaesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac arrest after suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their unpredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-06-01

Among all the drugs used for general anesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalemic cardiac arrest suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their upredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

The Influence of Robotic Assistance on Reducing Neuromuscular Effort and Fatigue during Extravehicular Activity Glove Use

NASA Technical Reports Server (NTRS)

Madden, Kaci E.; Deshpande, Ashish D.; Peters, Benjamin J.; Rogers, Jonathan M.; Laske, Evan A.; McBryan, Emily R.

2017-01-01

The three-layered, pressurized space suit glove worn by Extravehicular Activity (EVA) crew members during missions commonly causes hand and forearm fatigue. The Spacesuit RoboGlove (SSRG), a Phase VI EVA space suit glove modified with robotic grasp-assist capabilities, has been developed to augment grip strength in order to improve endurance and reduce the risk of injury in astronauts. The overall goals of this study were to i) quantify the neuromuscular modulations that occur in response to wearing a conventional Phase VI space suit glove (SSG) during a fatiguing task, and ii) determine the efficacy of Spacesuit RoboGlove (SSRG) in reversing the adverse neuromuscular modulations and restoring altered muscular activity to barehanded levels. Six subjects performed a fatigue sequence consisting of repetitive dynamic-gripping interspersed with isometric grip-holds under three conditions: barehanded, wearing pressurized SSG, and wearing pressurized SSRG. Surface electromyography (sEMG) from six forearm muscles (flexor digitorum superficialis (FDS), flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), extensor digitorum (ED), extensor carpi radialis longus (ECRL), and extensor carpi ulnaris (ECU)) and subjective fatigue ratings were collected during each condition. Trends in amplitude and spectral distributions of the sEMG signals were used to derive metrics quantifying neuromuscular effort and fatigue that were compared across the glove conditions. Results showed that by augmenting finger flexion, the SSRG successfully reduced the neuromuscular effort needed to close the fingers of the space suit glove in more than half of subjects during two types of tasks. However, the SSRG required more neuromuscular effort to extend the fingers compared to a conventional SSG in many subjects. Psychologically, the SSRG aided subjects in feeling less fatigued during short periods of intense work compared to the SSG. The results of this study reveal the promise of the SSRG as a grasp-assist device that can improve astronaut performance and reduce the risk of injury by offsetting neuromuscular effort. Modifications to the experimental protocol are needed, however, to improve the outcome of the neuromuscular fatigue metrics and determine the effectiveness of SSRG in increasing astronaut endurance. Nevertheless, these findings will improve the understanding of astronaut-spacesuit interaction and provide direction toward designing improved spacesuit gloves and robotic-assist devices, like the SSRG.

Achromatic and uncoupled medical gantry

DOEpatents

Tsoupas, Nicholaos [Center Moriches, NY; Kayran, Dmitry [Rocky Point, NY; Litvinenko, Vladimir [Mt. Sinai, NY; MacKay, William W [Wading River, NY

2011-11-22

A medical gantry that focus the beam from the beginning of the gantry to the exit of the gantry independent of the rotation angle of the gantry by keeping the beam achromatic and uncoupled, thus, avoiding the use of collimators or rotators, or additional equipment to control the beam divergence, which may cause beam intensity loss or additional time in irradiation of the patient, or disadvantageously increase the overall gantry size inapplicable for the use in the medical treatment facility.

Overexpression of uncoupling protein-2 in cancer: metabolic and heat changes, inhibition and effects on drug resistance.

PubMed

Pitt, Michael A

2015-12-01

This paper deals with the role of uncoupling protein-2 (UCP2) in cancer. UCP2 is overexpressed in cancer. This overexpression results in uncoupling of mitochondrial oxidative phosphorylation and a shift in production of ATP from mitochondrial oxidative phosphorylation to cytosolic aerobic glycolysis. UCP2 overexpression results in the following changes. Mitochondrial membrane potential (Δψ(m)) is decreased and lactate accumulates. There is a diminished production of reactive oxygen species and apoptosis is inhibited post-exposure to chemotherapeutic agents. There is an increase in heat and entropy production and a departure from the stationary state of non-cancerous tissue. Uncoupling of oxidative phosphorylation may also be caused by protonophores and non-steroidal anti-inflammatory drugs. UCP2 requires activation by superoxide and lipid peroxidation derivatives. As vitamin E inhibits lipid peroxidation, it might be expected that vitamin E would act as a chemotherapeutic agent against cancer. A recent study has shown that vitamin E and another anti-oxidant accelerate cancer progression. UCP2 is inhibited by genipin, chromane compounds and short interfering RNAs (siRNA). Genipin, chromanes and siRNA are taken up by both cancer and non-cancerous cells. Targeting the uptake of these agents by cancer cells by the enhanced permeability and retention effect is considered. Inhibition of UCP2 enhances the action of several anti-cancer agents.

Application of a personal computer for the uncoupled vibration analysis of wind turbine blade and counterweight assemblies

NASA Technical Reports Server (NTRS)

White, P. R.; Little, R. R.

1985-01-01

A research effort was undertaken to develop personal computer based software for vibrational analysis. The software was developed to analytically determine the natural frequencies and mode shapes for the uncoupled lateral vibrations of the blade and counterweight assemblies used in a single bladed wind turbine. The uncoupled vibration analysis was performed in both the flapwise and chordwise directions for static rotor conditions. The effects of rotation on the uncoupled flapwise vibration of the blade and counterweight assemblies were evaluated for various rotor speeds up to 90 rpm. The theory, used in the vibration analysis codes, is based on a lumped mass formulation for the blade and counterweight assemblies. The codes are general so that other designs can be readily analyzed. The input for the codes is generally interactive to facilitate usage. The output of the codes is both tabular and graphical. Listings of the codes are provided. Predicted natural frequencies of the first several modes show reasonable agreement with experimental results. The analysis codes were originally developed on a DEC PDP 11/34 minicomputer and then downloaded and modified to run on an ITT XTRA personal computer. Studies conducted to evaluate the efficiency of running the programs on a personal computer as compared with the minicomputer indicated that, with the proper combination of hardware and software options, the efficiency of using a personal computer exceeds that of a minicomputer.

Myocardial architecture and patient variability in clinical patterns of atrial fibrillation

NASA Astrophysics Data System (ADS)

Manani, Kishan A.; Christensen, Kim; Peters, Nicholas S.

2016-10-01

Atrial fibrillation (AF) increases the risk of stroke by a factor of 4-5 and is the most common abnormal heart rhythm. The progression of AF with age, from short self-terminating episodes to persistence, varies between individuals and is poorly understood. An inability to understand and predict variation in AF progression has resulted in less patient-specific therapy. Likewise, it has been a challenge to relate the microstructural features of heart muscle tissue (myocardial architecture) with the emergent temporal clinical patterns of AF. We use a simple model of activation wave-front propagation on an anisotropic structure, mimicking heart muscle tissue, to show how variation in AF behavior arises naturally from microstructural differences between individuals. We show that the stochastic nature of progressive transversal uncoupling of muscle strands (e.g., due to fibrosis or gap junctional remodeling), as occurs with age, results in variability in AF episode onset time, frequency, duration, burden, and progression between individuals. This is consistent with clinical observations. The uncoupling of muscle strands can cause critical architectural patterns in the myocardium. These critical patterns anchor microreentrant wave fronts and thereby trigger AF. It is the number of local critical patterns of uncoupling as opposed to global uncoupling that determines AF progression. This insight may eventually lead to patient-specific therapy when it becomes possible to observe the cellular structure of a patient's heart.

[Ocular disturbances in neuromuscular disorders].

PubMed

Pénisson-Besnier, I; Lamirel, C

2008-11-01

Compared with other skeletal muscles, extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain neuromuscular disorders. When the oculomotor signs are predominant, their temporal progression allows the clinician to make the distinction between a muscular disease (mitochondrial disorder, oculopharyngeal muscular dystrophy...) and a disorder of the neuromuscular junction (myasthenia gravis, botulism...). In other instances, such as myotonic dystrophy or facioscapulohumeral dystrophy, the ocular signs are not in the forefront but must be recognized by the ophthalmologist as hallmarks of a muscular disorder. In all cases, the collaboration between the neurologist and the ophthalmologist is fruitful.

Serum matrix metalloproteinase-3 levels are elevated in myasthenia gravis.

PubMed

Romi, Fredrik R; Gilhus, Nils Erik; Luckman, Steven P

2008-03-01

MMP-3 is capable of degrading a variety of proteins, including agrin, which plays a critical role in neuromuscular signalling by controlling acetylcholine receptor clustering. The degradation of agrin by MMP-3 may disrupt the neuromuscular junction leading to a failure of neuromuscular transmission and muscle weakness. We have therefore examined the levels of MMP-3 in 116 patients with myasthenia gravis (MG) and 90 healthy controls. A significant elevation in MMP-3 levels was observed in 10% of seronegative and 17% of seropositive MG patients, indicating that MMP-3 may play a pathogenic role in a proportion of MG patients.

Fatigue and neuromuscular diseases.

PubMed

Féasson, L; Camdessanché, J-P; El Mandhi, L; Calmels, P; Millet, G-Y

2006-07-01

To identify the role of fatigue, its evaluation and its causes in the pathophysiology context of acquired or hereditary neuromuscular diseases of the spinal anterior horn cell, peripheral nerve, neuromuscular junction and muscle. A literature review has been done on Medline with the following keywords: neuromuscular disease, peripheral neuropathy, myopathy, fatigue assessment, exercise intolerance, force assessment, fatigue scale and questionnaire, then with the terms: Fatigue Severity Scale, Chalder Fatigue Scale, Fatigue Questionnaire, Piper Fatigue Scale, electromyography and the combination of the word Fatigue with the following terms: Amyotrophic Lateral Sclerosis (ALS), Post-Polio Syndrome (PPS), Guillain-Barre Syndrome, Immune Neuropathy, Charcot-Marie-Tooth Disease, Myasthenia Gravis (MG), Metabolic Myopathy, Mitochondrial Myopathy, Muscular Dystrophy, Facioscapulohumeral Dystrophy, Myotonic Dystrophy. Fatigue is a symptom very frequently reported by patients. Fatigue is mainly evaluated by strength loss after an exercise, by change in electromyographic activity during a given exercise and by questionnaires that takes into account the subjective (psychological) part of fatigue. Due to the large diversity of motor disorders, there are multiple clinical expressions of fatigue that differ in their presentation, consequences and therapeutic approach. This review shows that fatigue has to be taken into account in patients with neuromuscular diseases. In this context, pathophysiology of fatigue often implies the motor component but the disease evolution and the physical obligates of daily life also induce an important psychological component.

A theoretical framework for understanding neuromuscular response to lower extremity joint injury.

PubMed

Pietrosimone, Brian G; McLeod, Michelle M; Lepley, Adam S

2012-01-01

Neuromuscular alterations are common following lower extremity joint injury and often lead to decreased function and disability. These neuromuscular alterations manifest in inhibition or abnormal facilitation of the uninjured musculature surrounding an injured joint. Unfortunately, these neural alterations are poorly understood, which may affect clinical recognition and treatment of these injuries. Understanding how these neural alterations affect physical function may be important for proper clinical management of lower extremity joint injuries. Pertinent articles focusing on neuromuscular consequences and treatment of knee and ankle injuries were collected from peer-reviewed sources available on the Web of Science and Medline databases from 1975 through 2010. A theoretical model to illustrate potential relationships between neural alterations and clinical impairments was constructed from the current literature. Lower extremity joint injury affects upstream cortical and spinal reflexive excitability pathways as well as downstream muscle function and overall physical performance. Treatment targeting the central nervous system provides an alternate means of treating joint injury that may be effective for patients with neuromuscular alterations. Disability is common following joint injury. There is mounting evidence that alterations in the central nervous system may relate to clinical changes in biomechanics that may predispose patients to further injury, and novel clinical interventions that target neural alterations may improve therapeutic outcomes.

A Theoretical Framework for Understanding Neuromuscular Response to Lower Extremity Joint Injury

PubMed Central

Pietrosimone, Brian G.; McLeod, Michelle M.; Lepley, Adam S.

2012-01-01

Background: Neuromuscular alterations are common following lower extremity joint injury and often lead to decreased function and disability. These neuromuscular alterations manifest in inhibition or abnormal facilitation of the uninjured musculature surrounding an injured joint. Unfortunately, these neural alterations are poorly understood, which may affect clinical recognition and treatment of these injuries. Understanding how these neural alterations affect physical function may be important for proper clinical management of lower extremity joint injuries. Methods: Pertinent articles focusing on neuromuscular consequences and treatment of knee and ankle injuries were collected from peer-reviewed sources available on the Web of Science and Medline databases from 1975 through 2010. A theoretical model to illustrate potential relationships between neural alterations and clinical impairments was constructed from the current literature. Results: Lower extremity joint injury affects upstream cortical and spinal reflexive excitability pathways as well as downstream muscle function and overall physical performance. Treatment targeting the central nervous system provides an alternate means of treating joint injury that may be effective for patients with neuromuscular alterations. Conclusions: Disability is common following joint injury. There is mounting evidence that alterations in the central nervous system may relate to clinical changes in biomechanics that may predispose patients to further injury, and novel clinical interventions that target neural alterations may improve therapeutic outcomes. PMID:23016066

In vivo imaging of skeletal muscle in mice highlights muscle defects in a model of myotubular myopathy

PubMed Central

Mercier, Luc; Böhm, Johann; Fekonja, Nina; Allio, Guillaume; Lutz, Yves; Koch, Marc; Goetz, Jacky G.; Laporte, Jocelyn

2016-01-01

ABSTRACT Skeletal muscle structure and function are altered in different myopathies. However, the understanding of the molecular and cellular mechanisms mainly rely on in vitro and ex vivo investigations in mammalian models. In order to monitor in vivo the intracellular structure of the neuromuscular system in its environment under normal and pathological conditions, we set-up and validated non-invasive imaging of ear and leg muscles in mice. This original approach allows simultaneous imaging of different cellular and intracellular structures such as neuromuscular junctions and sarcomeres, reconstruction of the 3D architecture of the neuromuscular system, and video recording of dynamic events such as spontaneous muscle fiber contraction. Second harmonic generation was combined with vital dyes and fluorescent-coupled molecules. Skin pigmentation, although limiting, did not prevent intravital imaging. Using this versatile toolbox on the Mtm1 knockout mouse, a model for myotubular myopathy which is a severe congenital myopathy in human, we identified several hallmarks of the disease such as defects in fiber size and neuromuscular junction shape. Intravital imaging of the neuromuscular system paves the way for the follow-up of disease progression or/and disease amelioration upon therapeutic tests. It has also the potential to reduce the number of animals needed to reach scientific conclusions. PMID:28243519

Administration of magnesium sulphate before rocuronium: effects on speed of onset and duration of neuromuscular block.

PubMed

Kussman, B; Shorten, G; Uppington, J; Comunale, M E

1997-07-01

The speeds of onset of pancuronium, atracurium and vecuronium are increased by prior administration of magnesium sulphate. A prospective, randomized, double-blind, controlled, clinical study was performed to examine the effects of prior i.v. administration of magnesium sulphate 60 mg kg-1 on the neuromuscular blocking effects of rocuronium 0.6 mg kg-1 during isoflurane anaesthesia. Neuromuscular function was measured electromyographically (Relaxograph) in 30 patients who received either magnesium sulphate 60 mg kg-1 or normal saline, 1-min before rocuronium 0.6 mg kg-1. Mean onset times were similar in the two groups (magnesium sulphate 71 (SD 20) s; normal saline 75 (23) s), but times to initial, 10% and 25% recovery from neuromuscular block were significantly longer in the magnesium sulphate group (42.1 (16.3), 49.0 (12.4) and 56.5 (13.2) min, respectively) than in the saline group (25.1 (9.1), 33.0 (11.1) and 35.6 (13.2) min, respectively) (P < 0.05 in all three cases). Administration of magnesium sulphate was not associated with adverse haemodynamic effects. Prior administration of magnesium sulphate, under the study conditions described, prolonged rocuronium-induced neuromuscular block but did not increase speed of onset.

Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3.

PubMed

Wadman, Renske I; Vrancken, Alexander F J E; van den Berg, Leonard H; van der Pol, W Ludo

2012-11-13

Spinal muscular atrophy (SMA) is pathologically characterized by degeneration of anterior horn cells. Recent observations in animal models of SMA and muscle tissue from patients with SMA suggest additional abnormalities in the development and maturation of the neuromuscular junction. We therefore evaluated neuromuscular junction function in SMA with repetitive nerve stimulation. In this case-control study, repetitive nerve stimulation was performed in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls with motor neuron disease. Pathologic decremental responses (>10%) during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%) with SMA types 2 and 3, but not in healthy controls or controls with motor neuron disease. None of the patients or controls had an abnormal incremental response of >60%. The presence of an abnormal decremental response was not specific for the type of SMA, nor was it associated with compound muscle action potential amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type 3 who tried pyridostigmine reported increased stamina. These data suggest dysfunction of the neuromuscular junction in patients with SMA types 2 and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for evaluation in carefully designed, placebo-controlled, clinical trials.

Patterns of anterior and posterior muscle chain interactions during high performance long-hang elements in gymnastics.

PubMed

von Laßberg, Christoph; Rapp, Walter; Krug, Jürgen

2014-06-01

In a prior study with high level gymnasts we could demonstrate that the neuromuscular activation pattern during the "whip-like" leg acceleration phases (LAP) in accelerating movement sequences on high bar, primarily runs in a consecutive succession from the bar (punctum fixum) to the legs (punctum mobile). The current study presents how the neuromuscular activation is represented during movement sequences that immediately follow the LAP by the antagonist muscle chain to generate an effective transfer of momentum for performing specific elements, based on the energy generated by the preceding LAP. Thirteen high level gymnasts were assessed by surface electromyography during high performance elements on high bar and parallel bars. The results show that the neuromuscular succession runs primarily from punctum mobile towards punctum fixum for generating the transfer of momentum. Additionally, further principles of neuromuscular interactions between the anterior and posterior muscle chain during such movement sequences are presented. The findings complement the understanding of neuromuscular activation patterns during rotational movements around fixed axes and will help to form the basis of more direct and better teaching methods regarding earlier optimization and facilitation of the motor learning process concerning fundamental movement requirements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Relationship between skin temperature and muscle activation during incremental cycle exercise.

PubMed

Priego Quesada, Jose I; Carpes, Felipe P; Bini, Rodrigo R; Salvador Palmer, Rosario; Pérez-Soriano, Pedro; Cibrián Ortiz de Anda, Rosa M

2015-02-01

While different studies showed that better fitness level adds to the efficiency of the thermoregulatory system, the relationship between muscular effort and skin temperature is still unknown. Therefore, the present study assessed the relationship between neuromuscular activation and skin temperature during cycle exercise. Ten physically active participants performed an incremental workload cycling test to exhaustion while neuromuscular activations were recorded (via surface electromyography - EMG) from rectus femoris, vastus lateralis, biceps femoris and gastrocnemius medialis. Thermographic images were recorded before, immediately after and 10 min after finishing the cycling test, at four body regions of interest corresponding to the muscles where neuromuscular activations were monitored. Frequency band analysis was conducted to assess spectral properties of EMG signals in order to infer on priority in recruitment of motor units. Significant inverse relationship between changes in skin temperature and changes in overall neuromuscular activation for vastus lateralis was observed (r<-0.5 and p<0.04). Significant positive relationship was observed between skin temperature and low frequency components of neuromuscular activation from vastus lateralis (r>0.7 and p<0.01). Participants with larger overall activation and reduced low frequency component for vastus lateralis activation presented a better adaptive response of their thermoregulatory system by showing fewer changes in skin temperature after incremental cycling test. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pivoting neuromuscular control and proprioception in females and males.

PubMed

Lee, Song Joo; Ren, Yupeng; Kang, Sang Hoon; Geiger, François; Zhang, Li-Qun

2015-04-01

Noncontact ACL injuries occur most commonly in pivoting sports and are much more frequent in females than in males. However, information on sex differences in proprioceptive acuity under weight-bearing and leg neuromuscular control in pivoting is scarce. The objective of this study was to investigate sex differences in pivoting neuromuscular control during strenuous stepping tasks and proprioceptive acuity under weight-bearing. 21 male and 22 female subjects were recruited to evaluate pivoting proprioceptive acuity under weight-bearing, and pivoting neuromuscular control (in terms of leg pivoting instability, stiffness, maximum internal and external pivoting angles, and entropy of time-to-peak EMG in lower limb muscles) during strenuous stepping tasks performed on a novel offaxis elliptical trainer. Compared to males, females had significantly lower proprioceptive acuity under weight-bearing in both internal and external pivoting directions, higher pivoting instability, larger maximum internal pivoting angle, lower leg pivoting stiffness, and higher entropy of time-to-peak EMG in the gastrocnemius muscles during strenuous stepping tasks with internal and external pivoting perturbations. Results of this study may help us better understand factors contributing to ACL injuries in females and males, develop training strategies to improve pivoting neuromuscular control and proprioceptive acuity, and potentially reduce ACL and lower-limb musculoskeletal injuries.

Technology to enhance physical rehabilitation of critically ill patients.

PubMed

Needham, Dale M; Truong, Alex D; Fan, Eddy

2009-10-01

Neuromuscular complications after critical illness are common and can be severe and persistent. To ameliorate complications, there is growing interest in starting physical medicine and rehabilitation therapy immediately after physiologic stabilization. The introduction of physical medicine and rehabilitation-related technology into the intensive care unit may help facilitate delivery of this therapy. Neuromuscular electrical stimulation therapy creates passive contraction of muscles through low-voltage electrical impulses delivered through skin electrodes placed over target muscles. Although neuromuscular electrical stimulation has not been studied in patients with acute critical illness, published guidelines based on available evidence suggest that neuromuscular electrical stimulation may be considered in intensive care unit patients who are at high risk of developing muscle weakness. Bedside cycle ergometry can provide range of motion and muscle strength training for intensive care unit patients who are either sedated or awake, and may help preserve muscle architecture and improve strength and function. Finally, custom-designed technological aids to assist with ambulating mechanically ventilated patients may reduce the human resource requirements and improve the safety and effectiveness of early mobilization in the intensive care unit. Physical medicine and rehabilitation-related technologies may play an important role in preventing and treating intensive care unit-acquired neuromuscular complications. Future studies are needed to evaluate their efficacy in intensive care unit patients.

Segmental Pedicle Screw Instrumentation and Fusion Only to L5 in the Surgical Treatment of Flaccid Neuromuscular Scoliosis.

PubMed

Takaso, Masashi; Nakazawa, Toshiyuki; Imura, Takayuki; Fukuda, Michinari; Takahashi, Kazuhisa; Ohtori, Seiji

2018-03-01

A retrospective cohort study was performed. The purpose of this study was to determine the efficacy and safety of stopping segmental pedicle screw instrumentation constructs at L5 in the treatment of neuromuscular scoliosis. Duchenne muscular dystrophy and spinal muscular atrophy are flaccid neuromuscular disorders in which gradual deterioration is the hallmark and have a lot of characteristics in common despite differences in etiology. Instrumentation and fusion to the sacrum/pelvis has been a mainstay in the surgical treatment of flaccid neuromuscular scoliosis and recommended to correct pelvic obliquity. However, the caudal extent of instrumentation and fusion in the surgical treatment of flaccid neuromuscular scoliosis has remained a matter of considerable debate and there have been few studies on the use of segmental pedicle screw instrumentation for flaccid neuromuscular scoliosis. From 2005 to 2007, a total of 27 consecutive patients with neuromuscular disorders (20 Duchenne muscular dystrophy and 7 spinal muscular atrophy), aged 11 to 17 years, underwent segmental pedicle screw instrumentation and fusion only to L5. Assessment was performed clinically and with radiologic measurements. Minimum 2-year follow-up was required for inclusion in this study. Twenty patients were enrolled in this study. No patient was lost to follow-up. All patients had L5 tilt of less than 15° and a coronal curve with apex L2 or higher preoperatively. Preoperative coronal curve averaged 70° (range: 51°-88°), with a postoperative mean of 15° (range: 5°-25°) and 17° (range: 6°-27°) at the last follow-up. The pelvic obliquity improved from 15° (range: 9°-25°) preoperatively to 5° (range: 3°-8°) postoperatively and 6° (range: 3°-8°) at the last follow-up. The L5 tilt improved from 9° (range: 2°-14°) preoperatively to 2° (range: 0°-4°) postoperatively and 2° (range: 0°-5°) at the last follow-up. Physiologic sagittal plane alignment was recreated after surgery and maintained long-term. There was no significant loss of correction of coronal curve and pelvic obliquity. There was no major complication. Segmental pedicle screw instrumentation and fusion to L5 was safe and effective in patients with flaccid neuromuscular scoliosis with apex L2 or higher and minimal L5 tilt of less than 15°. Segmental pedicle screw instrumentation ending at L5 offered the ability to correct spinal deformity and pelvic obliquity initially, intermediate and even long-term, with no major complications. This method in appropriate patients can be a viable alternative to instrumentation and fusion to the sacrum/pelvis in the surgical treatment of flaccid neuromuscular scoliosis. N/A.

Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction

PubMed Central

Musicki, Biljana; Burnett, Arthur L.

2016-01-01

Erectile dysfunction (ED) associated with type 2 diabetes mellitus (T2DM) involves dysfunctional nitric oxide (NO) signaling and increased oxidative stress in the penis. However, the mechanisms of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) dysregulation, and the sources of oxidative stress, are not well defined, particularly at the human level. The objective of this study was to define whether uncoupled eNOS and nNOS, and NADPH oxidase upregulation, contribute to the pathogenesis of ED in T2DM men. Penile erectile tissue was obtained from 9 T2DM patients with ED who underwent penile prosthesis surgery for ED, and from 6 control patients without T2DM or ED who underwent penectomy for penile cancer. The dimer-to-monomer protein expression ratio, an indicator of uncoupling for both eNOS and nNOS, total protein expressions of eNOS and nNOS, as well as protein expressions of NADPH oxidase catalytic subunit gp91phox (an enzymatic source of oxidative stress) and 4-hydroxy-2-nonenal [4-HNE] and nitrotyrosine (markers of oxidative stress) were measured by Western blot in this tissue. In the erectile tissue of T2DM men, eNOS and nNOS uncoupling and protein expressions of NADPH oxidase subunit gp91phox, 4-HNE- and nitrotyrosine-modified proteins were significantly (p<0.05) increased compared to control values. Total eNOS and nNOS protein expressions were not significantly different between the groups. In conclusion, mechanisms of T2DM-associated ED in the human penis may involve uncoupled eNOS and nNOS and NADPH oxidase upregulation. Our description of molecular factors contributing to the pathogenesis of T2DM-associated ED at the human level is relevant for advancing clinically therapeutic approaches to restore erectile function in T2DM patients. PMID:28076881

Dynamic Flexibility and Proprioceptive Neuromuscular Facilitation.

ERIC Educational Resources Information Center

Hardy, Lew; Jones, David

1986-01-01

Two experiments are described which investigated whether results obtained in studies of static flexibility tranfer to dynamic flexibility. In both experiments, subjects were assigned to a group receiving proprioceptive neuromuscular facilitation training, ballistic stretching technique training or a control group. Results are presented and…

Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults

USDA-ARS?s Scientific Manuscript database

Background. Age-related alterations of neuromuscular activation may contribute to deficits in muscle power and mobility function. This study assesses whether impaired activation of the agonist quadriceps and antagonist hamstrings, including amplitude- and velocity-dependent characteristics of activa...

Robots Would Couple And Uncouple Fluid And Electrical Lines

NASA Technical Reports Server (NTRS)

Del Castillo, Eduardo Lopez; Davis, Virgil; Ferguson, Bob; Reichle, Garland

1992-01-01

Robots make and break connections between umbilical plates and mating connectors on rockets about to be launched. Sensing and control systems include vision, force, and torque subsystems. Enhances safety by making it possible to couple and uncouple umbilical plates quickly, without exposing human technicians to hazards of leaking fuels and oxidizers. Significantly reduces time spent to manually connect umbilicals. Robots based on similar principles used in refueling of National AeroSpace Plane (NASP) and satellites and orbital transfer vehicles in space.

Time course and dimensions of postural control changes following neuromuscular training in youth field hockey athletes.

PubMed

Zech, Astrid; Klahn, Philipp; Hoeft, Jon; zu Eulenburg, Christine; Steib, Simon

2014-02-01

Injury prevention effects of neuromuscular training have been partly attributed to postural control adaptations. Uncertainty exists regarding the magnitude of these adaptations and on how they can be adequately monitored. The objective was to determine the time course of neuromuscular training effects on functional, dynamic and static balance measures. Thirty youth (14.9 ± 3 years) field hockey athletes were randomised to an intervention or control group. The intervention included a 20-min neuromuscular warm-up program performed twice weekly for 10 weeks. Balance assessments were performed at baseline, week three, week six and post-intervention. They included the star excursion balance test (SEBT), balance error scoring system (BESS), jump-landing time to stabilization (TTS) and center of pressure (COP) sway velocity during single-leg standing. No baseline differences were found between groups in demographic data and balance measures. Adherence was at 86%. All balance measures except the medial-lateral TTS improved significantly over time (p < 0.05) in both groups. Significant group by time interactions were found for the BESS score (p < 0.001). The intervention group showed greater improvements (69.3 ± 10.3%) after 10 weeks in comparison to controls (31.8 ± 22.1%). There were no significant group by time interactions in the SEBT, TTS and COP sway velocity. Neuromuscular training was effective in improving postural control in youth team athletes. However, this effect was not reflected in all balance measures suggesting that the neuromuscular training did not influence all dimensions of postural control. Further studies are needed to confirm the potential of specific warm-up programs to improve postural control.

Neuromuscular partitioning in the extensor carpi radialis longus and brevis based on intramuscular nerve distribution patterns: A three-dimensional modeling study.

PubMed

Ravichandiran, Mayoorendra; Ravichandiran, Nisanthini; Ravichandiran, Kajeandra; McKee, Nancy H; Richardson, Denyse; Oliver, Michele; Agur, Anne M

2012-04-01

Differential activation of specific regions within a skeletal muscle has been linked to the presence of neuromuscular compartments. However, few studies have investigated the extra- or intramuscular innervation throughout the muscle volume of extensor carpi radialis longus (ECRL) and brevis (ECRB). The aim of this study was to determine the presence of neuromuscular partitions in ECRL and ECRB based on the extra- and intramuscular innervation using three-dimensional modeling. The extra- and intramuscular nerve distribution was digitized and reconstructed in 3D in all the muscle volumes using Autodesk Maya in seven formalin embalmed cadaveric specimens (mean age, 75.7 ± 15.2 years). The intramuscular nerve distribution was modeled in all the muscle volumes. ECRL was found to have two neuromuscular compartments, superficial and deep. One branch from the radial nerve proper was found to innervate ECRL. This branch was divided into anterior and posterior branches to the superficial and deep compartments, respectively. Five innervation patterns were identified in ECRB with partitioning of the muscle belly into two, three, or four compartments, in a proximal to distal direction depending on the number of nerve branches entering the muscle belly. The ECRL and ECRB both demonstrated neuromuscular compartmentalization based on intramuscular innervation. According to the partitioning hypothesis, a muscle may be differentially activated depending on the required function of the muscle, thus allowing multifunctional muscles to contribute to a variety of movements. Therefore, the increased number of neuromuscular partitions in ECRB when compared with ECRL could be due to the need for more differential recruitment in the ECRB depending on force requirements. Copyright © 2011 Wiley Periodicals, Inc.

S-Nitrosoglutathione Reductase Deficiency-Induced S-Nitrosylation Results in Neuromuscular Dysfunction

PubMed Central

Montagna, Costanza; Di Giacomo, Giuseppina; Rizza, Salvatore; Cardaci, Simone; Ferraro, Elisabetta; Grumati, Paolo; De Zio, Daniela; Maiani, Emiliano; Muscoli, Carolina; Lauro, Filomena; Ilari, Sara; Bernardini, Sergio; Cannata, Stefano; Gargioli, Cesare; Ciriolo, Maria R.; Cecconi, Francesco; Bonaldo, Paolo

2014-01-01

Abstract Aims: Nitric oxide (NO) production is implicated in muscle contraction, growth and atrophy, and in the onset of neuropathy. However, many aspects of the mechanism of action of NO are not yet clarified, mainly regarding its role in muscle wasting. Notably, whether NO production-associated neuromuscular atrophy depends on tyrosine nitration or S-nitrosothiols (SNOs) formation is still a matter of debate. Here, we aim at assessing this issue by characterizing the neuromuscular phenotype of S-nitrosoglutathione reductase-null (GSNOR-KO) mice that maintain the capability to produce NO, but are unable to reduce SNOs. Results: We demonstrate that, without any sign of protein nitration, young GSNOR-KO mice show neuromuscular atrophy due to loss of muscle mass, reduced fiber size, and neuropathic behavior. In particular, GSNOR-KO mice show a significant decrease in nerve axon number, with the myelin sheath appearing disorganized and reduced, leading to a dramatic development of a neuropathic phenotype. Mitochondria appear fragmented and depolarized in GSNOR-KO myofibers and myotubes, conditions that are reverted by N-acetylcysteine treatment. Nevertheless, although atrogene transcription is induced, and bulk autophagy activated, no removal of damaged mitochondria is observed. These events, alongside basal increase of apoptotic markers, contribute to persistence of a neuropathic and myopathic state. Innovation: Our study provides the first evidence that GSNOR deficiency, which affects exclusively SNOs reduction without altering nitrotyrosine levels, results in a clinically relevant neuromuscular phenotype. Conclusion: These findings provide novel insights into the involvement of GSNOR and S-nitrosylation in neuromuscular atrophy and neuropathic pain that are associated with pathological states; for example, diabetes and cancer. Antioxid. Redox Signal. 21, 570–587. PMID:24684653

Influence of neuromuscular noise and walking speed on fall risk and dynamic stability in a 3D dynamic walking model.

PubMed

Roos, Paulien E; Dingwell, Jonathan B

2013-06-21

Older adults and those with increased fall risk tend to walk slower. They may do this voluntarily to reduce their fall risk. However, both slower and faster walking speeds can predict increased risk of different types of falls. The mechanisms that contribute to fall risk across speeds are not well known. Faster walking requires greater forward propulsion, generated by larger muscle forces. However, greater muscle activation induces increased signal-dependent neuromuscular noise. These speed-related increases in neuromuscular noise may contribute to the increased fall risk observed at faster walking speeds. Using a 3D dynamic walking model, we systematically varied walking speed without and with physiologically-appropriate neuromuscular noise. We quantified how actual fall risk changed with gait speed, how neuromuscular noise affected speed-related changes in fall risk, and how well orbital and local dynamic stability measures predicted changes in fall risk across speeds. When we included physiologically-appropriate noise to the 'push-off' force in our model, fall risk increased with increasing walking speed. Changes in kinematic variability, orbital, and local dynamic stability did not predict these speed-related changes in fall risk. Thus, the increased neuromuscular variability that results from increased signal-dependent noise that is necessitated by the greater muscular force requirements of faster walking may contribute to the increased fall risk observed at faster walking speeds. The lower fall risk observed at slower speeds supports experimental evidence that slowing down can be an effective strategy to reduce fall risk. This may help explain the slower walking speeds observed in older adults and others. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study

PubMed Central

Duyff, R.; Van den Bosch, J.; Laman, D; van Loon, B.-J. P.; Linssen, W.

2000-01-01

OBJECTIVES—To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism.
METHODS—A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment.
RESULTS—In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6months).
CONCLUSIONS—Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

 PMID:10811699

Prevalence of neuromuscular disorders in Qena governorate/Egypt: population-based survey.

PubMed

Khedr, Eman M; Fawi, Gharib; Abbas, Mohammed Abd-Allah; Abo El-Fetoh, Noha; Zaki, Ahmed F; Gamea, Ayman; Al Attar, Ghada

2016-12-01

Few epidemiological studies of the prevalence of neuromuscular disorders have been undertaken. The aim of the study was to estimate the prevalence of the most common types of neuromuscular disorders in Qena governorate/Egypt. A random sample was taken from 11 districts, involving 9303 inhabitants with 57.3% urban residents and 42.7% rural residence. Patients were diagnosed using a screening questionnaire for the diagnosis of neuromuscular disorders. All positive cases were referred to Qena University hospital where they underwent full clinical, electrophysiological, and laboratory investigations. Out of 9303 participants 448 cases were identified positive during survey. Four hundred and twenty-six cases proved to have neuromuscular disorders giving a crude prevalence rate (CPR) of 4.57%; 408 cases had definite neuropathy and 18 cases had muscular disorders equivalent to CPR of 4.39% and 193/10 5 respectively. There was a higher prevalence in the rural than urban population. The CPR of focal compression neuropathies was 1.8%, with the majority of cases having carpal tunnel syndrome (CPR = 1.67%). CPR of diabetic neuropathy was 1.67%. The CPR of compressive radiculopathy was 0.34%. Traumatic nerve injury had a CPR 0.06%. The lifetime prevalence of Bell's palsy was 0.16%. Hereditary motor and sensory neuropathy had a CPR 0.08%. The CPR of idiopathic neuropathy was 0.09% and Infective Leprotic neuropathy was 0.04%. Five patients were diagnosed as having muscular dystrophy and another 5 patients had myotonia with CPR of 54/10 5 for each. Two cases of myasthenia gravis and another two cases with systemic myopathy were recorded giving a CPR of 21/10 5 . The overall CPR of neuromuscular disorders in the general population in Qena governorate/Egypt was higher than reported in other countries.

Effects of Neuromuscular Fatigue on Quadriceps Strength and Activation and Knee Biomechanics in Individuals Post-Anterior Cruciate Ligament Reconstruction and Healthy Adults.

PubMed

Thomas, Abbey C; Lepley, Lindsey K; Wojtys, Edward M; McLean, Scott G; Palmieri-Smith, Riann M

2015-12-01

Laboratory-based experiment using a pretest/posttest design. To determine the effects of neuromuscular fatigue on quadriceps strength and activation and sagittal and frontal plane knee biomechanics during dynamic landing following anterior cruciate ligament reconstruction (ACLR). Impaired quadriceps central activation occurs post-ACLR, likely altering lower extremity biomechanics. Neuromuscular fatigue similarly reduces volitional muscle activation and impairs neuromuscular control. Upon return to full activity post-ACLR, individuals likely concurrently experience quadriceps central activation deficits and neuromuscular fatigue, though the effects of fatigue on muscle strength and activation and biomechanics post-ACLR are unknown. Seventeen individuals 7 to 10 months post-ACLR and 16 controls participated. Quadriceps strength and central activation ratio were recorded prefatigue and postfatigue, which was induced via sets of double-leg squats. Knee biomechanics were recorded during a dynamic landing activity prefatigue and postfatigue. Both groups demonstrated smaller knee flexion (initial contact, P = .017; peak, P = .004) and abduction (initial contact, P = .005; peak, P = .009) angles postfatigue. The ACLR group had smaller peak knee flexion angles (P<.001) prefatigue and postfatigue than controls. Knee flexion moment was smaller in those post-ACLR than controls prefatigue (P<.001), but not postfatigue (P = .103). Controls had smaller knee flexion moments postfatigue (P = .001). Knee abduction moment was smaller in both groups postfatigue (P = .003). All participants demonstrated significantly lower strength (P<.001) and activation (P = .003) postfatigue. Impaired strength, central activation, and biomechanics were present postfatigue in both groups, suggesting that neuromuscular fatigue may increase noncontact ACL injury risk. However, these changes were not exaggerated in those post-ACLR, likely because they already demonstrated a stiff-legged landing strategy prefatigue.

Effects of weight management program on postural stability and neuromuscular function among obese children: study protocol for a randomized controlled trial.

PubMed

Sun, Fenghua; Wang, Li-Juan; Wang, Lin

2015-04-10

Childhood obesity is one of the most critical public health problems in the world. It is associated with low neuromuscular function and postural deformities. Whether weight loss can improve postural stability and neuromuscular control, benefit daily activities, or prevent injury is unknown. Therefore, this study attempts to investigate the effect of a 6 month weight management program on postural stability and neuromuscular control among obese children. We will conduct a prospective, single-blind, randomized controlled trial with 120 prepubescent obese children. Participants will be randomly assigned to a weight management group or a control group. The weight management group will participate in a dietary and exercise program. The control group will receive health education. After the intervention, participants will be followed for 6 months with no active intervention. The primary and secondary outcomes will be assessed at the baseline, and after 6 months and 12 months. Primary outcome measures will include body weight, body height, body mass index, waist circumference, hip circumference, and body fat percentage. Secondary outcome measures will include three-dimensional functional biomechanics in different tasks, proprioception tests of the knee and ankle, neuromuscular response of the leg muscles, and muscle strength tests of the knee and ankle. Furthermore, adverse events will be recorded and analyzed. An intention-to-treat analysis will be performed if any participants withdraw from the trial. The important features of this trial include the randomization procedures and large sample size. This study attempts to estimate the effect of weight loss intervention on outcomes, including daily life function, postural stability, and neuromuscular control in prepubescent obese children. Therefore, our results can be useful for obese children, medical staff, and healthcare decision makers. Chinese Clinical Trial Registry ChiCTR-IOB-15005874.

Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study.

PubMed

Brueckmann, B; Sasaki, N; Grobara, P; Li, M K; Woo, T; de Bie, J; Maktabi, M; Lee, J; Kwo, J; Pino, R; Sabouri, A S; McGovern, F; Staehr-Rye, A K; Eikermann, M

2015-11-01

This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. Adult patients undergoing abdominal surgery received rocuronium, followed by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio <0.9, using TOF-Watch® SX. Key secondary endpoint was time between reversal agent administration and operating room discharge-readiness; analysed with analysis of covariance. Of 154 patients randomized, 150 had a TOF value measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P<0.0001). Of these 33 usual care patients, 2 also had clinical evidence of partial paralysis. Time between reversal agent administration and operating room discharge-readiness was shorter for sugammadex vs usual care (14.7 vs. 18.6 min respectively; P=0.02). After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU, and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room. Clinicaltrials.gov:NCT01479764. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

PubMed

Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

2016-06-01

Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

Testing rocuronium-induced neuromuscular blockade at the stapedius muscle using stapedius reflex measurements.

PubMed

Sárkány, P; Tassonyi, E; Nemes, R; Timkó, A; Pongrácz, A; Fülesdi, Béla

2011-12-01

Neuromuscular monitoring prior to emergence from anaesthesia has been shown to be necessary to achieve adequate airway protection in order to decrease postoperative pulmonary complications. In the present study we hypothesized that stapedius reflex measurement allows the detection of residual neuromuscular blockade using the stapedius muscle following the administration of rocuronium. Parallel stapedius and acceleromyographic measurements were performed on 20 patients undergoing cholecystectomy. Acceleromyographic measurements were continuously performed during the course of anaesthesia, whereas the stapedius reflex was measured on different occasions: (1) after premedication but before anaesthesia induction, (2) after induction, but before administration of muscle relaxant, (3) after administration of muscle relaxant, (4) during the course of surgical anaesthesia at regular intervals, and (5) continuously performed during emergence from anaesthesia, until the stapedius reflex threshold returned to normal. The intensity of the sound energy at which the stapedius reflex is detectable was similar: 89.5 ± 9.9 dB(mean ± SD) after premedication and after anaesthetic induction. However, after administration of rocuronium, when the twitch height decreased to 5%, the stapedius reflex disappeared, indicating a total block of the stapedius muscle.During the recovery phase (twitch>10%) significantly higher sound energies compared to baseline values were necessary to evoke the reflex, indicating residual inhibition of the stapedius muscle. At the point where stapedius reflex threshold returned to normal the twitch height averaged about 50% showing low sensitivity of the tympanometry in detecting residual neuromuscular blockade. The neuromuscular effect of rocuronium on the stapedius muscle can be detected using stapedius reflex measurements. Due to its methodological limitation and low sensitivity, the method cannot be recommended for the monitoring of residual neuromuscular blockade.

Influence of Neuromuscular Noise and Walking Speed on Fall Risk and Dynamic Stability in a 3D Dynamic Walking Model

PubMed Central

Roos, Paulien E.; Dingwell, Jonathan B.

2013-01-01

Older adults and those with increased fall risk tend to walk slower. They may do this voluntarily to reduce their fall risk. However, both slower and faster walking speeds can predict increased risk of different types of falls. The mechanisms that contribute to fall risk across speeds are not well known. Faster walking requires greater forward propulsion, generated by larger muscle forces. However, greater muscle activation induces increased signal-dependent neuromuscular noise. These speed-related increases in neuromuscular noise may contribute to the increased fall risk observed at faster walking speeds. Using a 3D dynamic walking model, we systematically varied walking speed without and with physiologically-appropriate neuromuscular noise. We quantified how actual fall risk changed with gait speed, how neuromuscular noise affected speed-related changes in fall risk, and how well orbital and local dynamic stability measures predicted changes in fall risk across speeds. When we included physiologically-appropriate noise to the ‘push-off’ force in our model, fall risk increased with increasing walking speed. Changes in kinematic variability, orbital, and local dynamic stability did not predict these speed-related changes in fall risk. Thus, the increased neuromuscular variability that results from increased signal-dependent noise that is necessitated by the greater muscular force requirements of faster walking may contribute to the increased fall risk observed at faster walking speeds. The lower fall risk observed at slower speeds supports experimental evidence that slowing down can be an effective strategy to reduce fall risk. This may help explain the slower walking speeds observed in older adults and others. PMID:23659911

Clindamycin-induced neuromuscular blockade.

PubMed

al Ahdal, O; Bevan, D R

1995-07-01

The purpose of this article is to report the case of a patient who developed prolonged neuromuscular block after a large dose of clindamycin (2400 mg). A 58-yr-old, 65 kg woman with severe rheumatoid arthritis was admitted for wrist arthrodesis. After d-tubocurarine (3 mg) and fentanyl (1.5 micrograms.kg-1), anaesthesia was induced with thiopentone (4 mg.kg-1) followed by succinylcholine (1.5 mg.kg-1) and was maintained with N2O in O2 and isoflurane (0.75-1.0% end tidal) and ventilation was controlled. No further neuromuscular relaxants were given although full return of neuromuscular activity in response to train-of-four and 100 Hz tetanic stimulation was observed after succinylcholine. An overdose of clindamycin (2400 mg, instead of the intended 600 mg) was given i.v. soon after the start of surgery. At the end of surgery, 75 min later, the patient made no attempt at spontaneous ventilation, was unresponsive to painful stimuli and naloxone (0.2 mg i.v.) was ineffective. Controlled ventilation was continued in the Recovery Room where neuromuscular testing showed a train-of-four ratio of 0.27 which improved to only 0.47 five minutes after calcium chloride (1.5 mg.kg-1 i.v.), and to 0.62 after edrophonium (20 mg) and neostigmine (2 mg). Nine hours later the patient began to cough, the TOF had returned to 1.0 and two hours later the trachea was extubated and spontaneous ventilation was resumed. Large doses of clindamycin can induce profound, long-lasting neuromuscular blockade in the absence of non-depolarizing relaxants and after full recovery from succinylcholine has been demonstrated.

Effectiveness of Neuromuscular Training Based on the Neuromuscular Risk Profile.

PubMed

Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D

2017-07-01

The effects of targeted neuromuscular training (TNMT) on movement biomechanics associated with the risk of anterior cruciate ligament (ACL) injuries are currently unknown. Purpose/Hypotheses: To determine the effectiveness of TNMT specifically designed to increase trunk control and hip strength. The hypotheses were that (1) TNMT would decrease biomechanical and neuromuscular factors related to an increased ACL injury risk and (2) TNMT would decrease these biomechanical and neuromuscular factors to a greater extent in athletes identified as being at a high risk for future ACL injuries. Controlled laboratory study. Female athletes who participated in jumping, cutting, and pivoting sports underwent 3-dimensional biomechanical testing before the season and after completing TNMT. During testing, athletes performed 3 different types of tasks: (1) drop vertical jump, (2) single-leg drop, and (3) single-leg cross drop. Analysis of covariance was used to examine the treatment effects of TNMT designed to enhance core and hip strength on biomechanical and neuromuscular characteristics. Differences were also evaluated by risk profile. Differences were considered statistically significant at P < .05. TNMT significantly increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. Athletes with a high risk before the intervention (risk profile III) had a more significant treatment effect of TNMT than low-risk groups (risk profiles I and II). TNMT significantly improved proximal biomechanics, including increased hip external rotation moments and moment impulses, increased peak trunk flexion, and decreased peak trunk extension. TNMT that focuses exclusively on proximal leg and trunk risk factors is not, however, adequate to induce significant changes in frontal-plane knee loading. Biomechanical changes varied across the risk profile groups, with higher risk groups exhibiting greater improvements in their biomechanics.

Endomicroscopy and electromyography of neuromuscular junctions in situ

PubMed Central

Brown, Rosalind; Dissanayake, Kosala N; Skehel, Paul A; Ribchester, Richard R

2014-01-01

Objective Electromyography (EMG) is used routinely to diagnose neuromuscular dysfunction in a wide range of peripheral neuropathies, myopathies, and neuromuscular degenerative diseases including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Definitive neurological diagnosis may also be indicated by the analysis of pathological neuromuscular innervation in motor-point biopsies. Our objective in this study was to preempt motor-point biopsy by combining live imaging with electrophysiological analysis of slow degeneration of neuromuscular junctions (NMJs) in vivo. Methods We combined conventional needle electromyography with fiber-optic confocal endomicroscopy (CEM), using an integrated hand-held, 1.5-mm-diameter probe. We utilized as a test bed, various axotomized muscles in the hind limbs of anaesthetized, double-homozygous thy1.2YFP16: WldS mice, which coexpress the Wallerian-degeneration Slow (WldS) protein and yellow fluorescent protein (YFP) in motor neurons. We also tested exogenous vital stains, including Alexa488-α-bungarotoxin; the styryl pyridinium dye 4-Di-2-Asp; and a GFP conjugate of botulinum toxin Type A heavy chain (GFP-HcBoNT/A). Results We show that an integrated EMG/CEM probe is effective in longitudinal evaluation of functional and morphological changes that take place over a 7-day period during axotomy-induced, slow neuromuscular synaptic degeneration. EMG amplitude declined in parallel with overt degeneration of motor nerve terminals. EMG/CEM was safe and effective when nerve terminals and motor endplates were selectively stained with vital dyes. Interpretation Our findings constitute proof-of-concept, based on live imaging in an animal model, that combining EMG/CEM may be useful as a minimally invasive precursor or alternative to motor-point biopsy in neurological diagnosis and for monitoring local administration of potential therapeutics. PMID:25540801

Genetics and Neuromuscular Diseases

MedlinePlus

... risk of passing on the disorder in these cases. It’s very likely that this kind of situation occurs in other neuromuscular genetic disorders, although most haven’t been as well studied as Duchenne dystrophy. For example, more than one sperm or egg cell could pass on a ...

Electrophysiological and neuromuscular stability of persons with chronic inflammatory demyelinating polyneuropathy.

PubMed

Gilmore, Kevin J; Allen, Matti D; Doherty, Timothy J; Kimpinski, Kurt; Rice, Charles L

2017-09-01

We assessed motor unit (MU) properties and neuromuscular stability in the tibialis anterior (TA) of chronic inflammatory demyelinating polyneuropathy (CIDP) patients using decomposition-based quantitative electromyography. Dorsiflexion strength was assessed, and surface and concentric needle electromyography were sampled from the TA. Estimates of MU numbers were derived using decomposition-based quantitative electromyography and spike-triggered averaging. Neuromuscular transmission stability was assessed from concentric needle-detected MU potentials. CIDP patients had 43% lower compound muscle action potential amplitude than controls, and despite near-maximum voluntary activation, were 37% weaker. CIDP had 27% fewer functioning MUs in the TA, and had 90% and 44% higher jiggle and jitter values, respectively compared with controls. CIDP had lower strength and compound muscle action potential values, moderately fewer numbers of MUs, and significant neuromuscular instability compared with controls. Thus, in addition to muscle atrophy, voluntary weakness is also due to limitations of peripheral neural transmission consistent with demyelination. Muscle Nerve 56: 413-420, 2017. © 2016 Wiley Periodicals, Inc.

Effects of regular Tai Chi practice and jogging on neuromuscular reaction during lateral postural control in older people.

PubMed

Wang, Shao-Jun; Xu, Dong-Qing; Li, Jing-Xian

2017-01-01

This study examined the effects of regular Tai Chi practice and jogging on the neuromuscular activity of the trunk, hip, and ankle joint muscles of older people during lateral postural perturbation. A total of 42 older people participated in the study and formed the Tai Chi, jogging, and sedentary control groups. Electromyography signals were collected from the peroneus longus, anterior tibialis, gluteus medius, and erector spinae during unpredictable mediolateral perturbation. The Tai Chi group exhibited significantly faster latencies of the tibialis anterior and erector spinae than the control group. The jogging group showed a significantly shorter neuromuscular reaction time of the erector spinae than the control group. No significant difference was observed between the Tai Chi and jogging groups. Long-term regular Tai Chi practice enhanced the neuromuscular reaction of the erector spinae and tibialis anterior to lateral perturbation and will help timely posture correction when lateral postural distributions occur.

Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models.

PubMed

Silva, M M; Lemos, J M; Coito, A; Costa, B A; Wigren, T; Mendonça, T

2014-01-01

This paper addresses the local identifiability and sensitivity properties of two classes of Wiener models for the neuromuscular blockade and depth of hypnosis, when drug dose profiles like the ones commonly administered in the clinical practice are used as model inputs. The local parameter identifiability was assessed based on the singular value decomposition of the normalized sensitivity matrix. For the given input signal excitation, the results show an over-parameterization of the standard pharmacokinetic/pharmacodynamic models. The same identifiability assessment was performed on recently proposed minimally parameterized parsimonious models for both the neuromuscular blockade and the depth of hypnosis. The results show that the majority of the model parameters are identifiable from the available input-output data. This indicates that any identification strategy based on the minimally parameterized parsimonious Wiener models for the neuromuscular blockade and for the depth of hypnosis is likely to be more successful than if standard models are used. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hader, H.; Gadoth, N.; Heifetz, H.

1983-11-01

The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients withmore » neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen.« less

BAG3 myofibrillar myopathy presenting with cardiomyopathy.

PubMed

Konersman, Chamindra G; Bordini, Brett J; Scharer, Gunter; Lawlor, Michael W; Zangwill, Steven; Southern, James F; Amos, Louella; Geddes, Gabrielle C; Kliegman, Robert; Collins, Michael P

2015-05-01

Myofibrillar myopathies (MFMs) are a heterogeneous group of neuromuscular disorders distinguished by the pathological hallmark of myofibrillar dissolution. Most patients present in adulthood, but mutations in several genes including BCL2-associated athanogene 3 (BAG3) cause predominantly childhood-onset disease. BAG3-related MFM is particularly severe, featuring weakness, cardiomyopathy, neuropathy, and early lethality. While prior cases reported either neuromuscular weakness or concurrent weakness and cardiomyopathy at onset, we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12). The phenotype comprised distal weakness and severe sensorimotor neuropathy. Nerve biopsy was primarily axonal with secondary demyelinating/remyelinating changes without "giant axons." Muscle biopsy showed extensive neuropathic changes that made myopathic changes difficult to interpret. Similar to previous cases, a p.Pro209Leu mutation in exon 3 of BAG3 was found. This case underlines the importance of evaluating for MFMs in patients with combined neuromuscular weakness and cardiomyopathy. Copyright © 2015 Elsevier B.V. All rights reserved.

Neuromuscular electric stimulation in patellofemoral dysfunction: literature review

PubMed Central

dos Santos, Ricardo Lucas; Souza, Márcia Leal São Pedro; dos Santos, Fernanda Andrade

2013-01-01

Patellofemoral dysfunction is a fairly common deficiency among young individuals that primarily affects females and may be characterized by pain, swelling and retropatellar crepitation. The purpose of this review of literature from the period between 2005 and 2011 was to systematize knowledge in relation to the increase in quadriceps muscle strength and pain relief in patients with patellofemoral dysfunction, using neuromuscular electrical stimulation and resistance exercises. The inclusion criteria were intervention articles from the past six years, in English, Spanish and Portuguese, which used muscle strengthening and neuromuscular electrical stimulation for rehabilitation obtained through searches in the electronic databases Medline and Lilacs and in the Bireme library. The bibliographic search yielded 28 references, of which nine were excluded in accordance with the aims and inclusion criteria while 16 articles were selected for reading of the abstracts and subsequent analysis. Mediumfrequency Neuromuscular Electrical Stimulation (NMES) can be used in association with resistance exercises as an adjuvant in the treatment of patellofemoral dysfunction (PFD), both to achieve muscle rebalance and for pain relief. PMID:24453645

Neuromuscular ultrasound in patients with carpal tunnel syndrome and normal nerve conduction studies.

PubMed

Aseem, Fazila; Williams, Jessica W; Walker, Francis O; Cartwright, Michael S

2017-06-01

Nerve conduction studies (NCS) are sensitive for carpal tunnel syndrome (CTS), but a small proportion of patients with clinical CTS have normal NCS. This retrospective study was designed to assess the neuromuscular ultrasound findings in a group of CTS patients. The electronic medical record was reviewed by a neurologist to identify patients who had a diagnosis of CTS with normal NCS, including either mixed median-ulnar comparison or transcarpal sensory studies, and complete neuromuscular ultrasound evaluation for CTS. Fourteen individuals (22 wrists) met all criteria. A total of 92.3% had median nerve cross-sectional area enlargement at the wrist (mean 16.3 mm 2 ), 100% had increased wrist-to-forearm median nerve area ratio (mean 2.4), 82.4% had decreased median nerve echogenicity, 75.0% had decreased median nerve mobility, and 7.1% had increased median nerve vascularity. A large proportion of patients with clinical CTS but normal NCS have abnormal neuromuscular ultrasound findings. Muscle Nerve 55: 913-915, 2017. © 2016 Wiley Periodicals, Inc.

Geraniol attenuates α-synuclein expression and neuromuscular impairment through increase dopamine content in MPTP intoxicated mice by dose dependent manner.

PubMed

Rekha, Karamkolly R; Selvakumar, Govindasamy P; Santha, Karunanithi; Inmozhi Sivakamasundari, Ramu

2013-11-01

Parkinson's disease (PD) is characterized by progressive loss of dopamine (DA) neurons in the nigrostriatal system and by the presence of Lewy bodies (LB), proteinaceous inclusions mainly composed of filamentous α-synuclein (α-Syn) aggregates. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was adopted to generate PD models in C57BL/6 mice. In the present study, we investigated the effect of geraniol (GE) against α-Syn aggregation on MPTP induced mouse model of PD in dose dependant manner. When pretreatment of GE improved neuromuscular impairment, TH expressions and decreases α-Syn expressions in MPTP intoxicated PD mice by dose dependent manner. In addition, we confirmed that sub-chronic administration of MPTP in mice leads to permanent neuromuscular deficits and depletion of dopamine and its metabolites. Our results suggest that GE is beneficial for the treatment of PD associated with neuromuscular disability and LB aggregation. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Architectural properties of the neuromuscular compartments in selected forearm skeletal muscles

PubMed Central

Liu, An-Tang; Liu, Ben-Li; Lu, Li-Xuan; Chen, Gang; Yu, Da-Zhi; Zhu, Lie; Guo, Rong; Dang, Rui-Shan; Jiang, Hua

2014-01-01

The purposes f this study were to (i) explore the possibility of splitting the selected forearm muscles into separate compartments in human subjects; (ii) quantify the architectural properties of each neuromuscular compartment; and (iii) discuss the implication of these properties in split tendon transfer procedures. Twenty upper limbs from 10 fresh human cadavers were used in this study. Ten limbs of five cadavers were used for intramuscular nerve study by modified Sihler's staining technique, which confirmed the neuromuscular compartments. The other 10 limbs were included for architectural analysis of neuromuscular compartments. The architectural features of the compartments including muscle weight, muscle length, fiber length, pennation angle, and sarcomere length were determined. Physiological cross-sectional area and fiber length/muscle length ratio were calculated. Five of the selected forearm muscles were ideal candidates for splitting, including flexor carpi ulnaris, flexor carpi radials, extensor carpi radialis brevis, extensor carpi ulnaris and pronator teres. The humeral head of pronator teres contained the longest fiber length (6.23 ± 0.31 cm), and the radial compartment of extensor carpi ulnaris contained the shortest (2.90 ± 0.28 cm). The ulnar compartment of flexor carpi ulnaris had the largest physiological cross-sectional area (5.17 ± 0.59 cm2), and the ulnar head of pronator teres had the smallest (0.67 ± 0.06 cm2). Fiber length/muscle length ratios of the neuromuscular compartments were relatively low (average 0.27 ± 0.09, range 0.18–0.39) except for the ulnar head of pronator teres, which had the highest one (0.72 ± 0.05). Using modified Sihler's technique, this research demonstrated that each compartment of these selected forearm muscles has its own neurovascular supply after being split along its central tendon. Data of the architectural properties of each neuromuscular compartment provide insight into the ‘design’ of their functional capability. In addition to improving our understanding of muscle anatomy and function, elucidation of forearm neuromuscular compartments architecture may ultimately provide information useful for selection of muscle subdivisions used in tendon transfer. PMID:24836406

The effects of neuromuscular exercise on medial knee joint load post-arthroscopic partial medial meniscectomy: 'SCOPEX', a randomised control trial protocol.

PubMed

Hall, Michelle; Hinman, Rana S; Wrigley, Tim V; Roos, Ewa M; Hodges, Paul W; Staples, Margaret; Bennell, Kim L

2012-11-27

Meniscectomy is a risk factor for knee osteoarthritis, with increased medial joint loading a likely contributor to the development and progression of knee osteoarthritis in this group. Therefore, post-surgical rehabilitation or interventions that reduce medial knee joint loading have the potential to reduce the risk of developing or progressing osteoarthritis. The primary purpose of this randomised, assessor-blind controlled trial is to determine the effects of a home-based, physiotherapist-supervised neuromuscular exercise program on medial knee joint load during functional tasks in people who have recently undergone a partial medial meniscectomy. 62 people aged 30-50 years who have undergone an arthroscopic partial medial meniscectomy within the previous 3 to 12 months will be recruited and randomly assigned to a neuromuscular exercise or control group using concealed allocation. The neuromuscular exercise group will attend 8 supervised exercise sessions with a physiotherapist and will perform 6 exercises at home, at least 3 times per week for 12 weeks. The control group will not receive the neuromuscular training program. Blinded assessment will be performed at baseline and immediately following the 12-week intervention. The primary outcomes are change in the peak external knee adduction moment measured by 3-dimensional analysis during normal paced walking and one-leg rise. Secondary outcomes include the change in peak external knee adduction moment during fast pace walking and one-leg hop and change in the knee adduction moment impulse during walking, one-leg rise and one-leg hop, knee and hip muscle strength, electromyographic muscle activation patterns, objective measures of physical function, as well as self-reported measures of physical function and symptoms and additional biomechanical parameters. The findings from this trial will provide evidence regarding the effect of a home-based, physiotherapist-supervised neuromuscular exercise program on medial knee joint load during various tasks in people with a partial medial meniscectomy. If shown to reduce the knee adduction moment, neuromuscular exercise has the potential to prevent the onset of osteoarthritis or slow its progression in those with early disease. Australian New Zealand Clinical Trials Registry reference: ACTRN12612000542897.

Regulation of thermogenesis in plants: the interaction of alternative oxidase and plant uncoupling mitochondrial protein.

PubMed

Zhu, Yan; Lu, Jianfei; Wang, Jing; Chen, Fu; Leng, Feifan; Li, Hongyu

2011-01-01

Thermogenesis is a process of heat production in living organisms. It is rare in plants, but it does occur in some species of angiosperm. The heat is generated via plant mitochondrial respiration. As possible involvement in thermogenesis of mitochondrial factors, alternative oxidases (AOXs) and plant uncoupling mitochondrial proteins (PUMPs) have been well studied. AOXs and PUMPs are ubiquitously present in the inner membrane of plant mitochondria. They serve as two major energy dissipation systems that balance mitochondrial respiration and uncoupled phosphorylation by dissipating the H+ redox energy and proton electrochemical gradient (ΔμH+) as heat, respectively. AOXs and PUMPs exert similar physiological functions during homeothermic heat production in thermogenic plants. AOXs have five isoforms, while PUMPs have six. Both AOXs and PUMPs are encoded by small nuclear multigene families. Multiple isoforms are expressed in different tissues or organs. Extensive studies have been done in the area of thermogenesis in higher plants. In this review, we focus on the involvement and regulation of AOXs and PUMPs in thermogenesis.

Skeletal Muscle Thermogenesis and Its Role in Whole Body Energy Metabolism

PubMed Central

Herrera, Jose Luis; Reis, Felipe C. G.

2017-01-01

Obesity and diabetes has become a major epidemic across the globe. Controlling obesity has been a challenge since this would require either increased physical activity or reduced caloric intake; both are difficult to enforce. There has been renewed interest in exploiting pathways such as uncoupling protein 1 (UCP1)-mediated uncoupling in brown adipose tissue (BAT) and white adipose tissue to increase energy expenditure to control weight gain. However, relying on UCP1-based thermogenesis alone may not be sufficient to control obesity in humans. On the other hand, skeletal muscle is the largest organ and a major contributor to basal metabolic rate and increasing energy expenditure in muscle through nonshivering thermogenic mechanisms, which can substantially affect whole body metabolism and weight gain. In this review we will describe the role of Sarcolipin-mediated uncoupling of Sarcoplasmic Reticulum Calcium ATPase (SERCA) as a potential mechanism for increased energy expenditure both during cold and diet-induced thermogenesis. PMID:29086530

Sludge reduction by uncoupling metabolism: SBR tests with para-nitrophenol and a commercial uncoupler.

PubMed

Zuriaga-Agustí, E; Mendoza-Roca, J A; Bes-Piá, A; Alonso-Molina, J L; Amorós-Muñoz, I

2016-11-01

Nowadays cost reduction is a very important issue in wastewater treatment plants. One way, is to minimize the sludge production. Microorganisms break down the organic matter into inorganic compounds through catabolism. Uncoupling metabolism is a method which promote catabolism reactions instead of anabolism ones, where adenosine triphosphate synthesis is inhibited. In this work, the influence of the addition of para-nitrophenol and a commercial reagent to a sequencing batch reactor (SBR) on sludge production and process performance has been analyzed. Three laboratory SBRs were operated in parallel to compare the effect of the addition of both reagents with a control reactor. SBRs were fed with synthetic wastewater and were operated with the same conditions. Results showed that sludge production was slightly reduced for the tested para-nitrophenol concentrations (20 and 25 mg/L) and for a LODOred dose of 1 mL/day. Biological process performance was not influenced and high COD removals were achieved. Copyright © 2016 Elsevier Ltd. All rights reserved.

Uncoupling effect of palmitate is exacerbated in skeletal muscle mitochondria of sea-acclimatized king penguins (Aptenodytes patagonicus).

PubMed

Rey, Benjamin; Duchamp, Claude; Roussel, Damien

2017-09-01

In king penguin juveniles, the environmental transition from a terrestrial to a marine habitat, occurring at fledging, drastically stimulates lipid catabolism and the remodelling of muscle mitochondria to sustain extensive swimming activity and thermoregulation in the cold circumpolar oceans. However, the exact nature of these mechanisms remains only partially resolved. Here we investigated, in vitro, the uncoupling effect of increasing doses of fatty acids in pectoralis muscle intermyofibrillar mitochondria isolated, either from terrestrial never-immersed or experimentally cold water immersed pre-fledging king penguins or from sea-acclimatized fledged penguins. Mitochondria exhibited much greater palmitate-induced uncoupling respiration and higher maximal oxidative capacity after acclimatization to marine life. Such effects were not reproduced experimentally after repeated immersions in cold water, suggesting that the plasticity of mitochondrial characteristics may not be primarily driven by cold exposure per se but by other aspects of sea acclimatization. Copyright © 2017. Published by Elsevier Inc.

Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification

PubMed Central

Dejonghe, Wim; Kuenen, Sabine; Mylle, Evelien; Vasileva, Mina; Keech, Olivier; Viotti, Corrado; Swerts, Jef; Fendrych, Matyáš; Ortiz-Morea, Fausto Andres; Mishev, Kiril; Delang, Simon; Scholl, Stefan; Zarza, Xavier; Heilmann, Mareike; Kourelis, Jiorgos; Kasprowicz, Jaroslaw; Nguyen, Le Son Long; Drozdzecki, Andrzej; Van Houtte, Isabelle; Szatmári, Anna-Mária; Majda, Mateusz; Baisa, Gary; Bednarek, Sebastian York; Robert, Stéphanie; Audenaert, Dominique; Testerink, Christa; Munnik, Teun; Van Damme, Daniël; Heilmann, Ingo; Schumacher, Karin; Winne, Johan; Friml, Jiří; Verstreken, Patrik; Russinova, Eugenia

2016-01-01

ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane. PMID:27271794

Graded activation of the intrinsic laryngeal muscles for vocal fold posturing

PubMed Central

Chhetri, Dinesh K.; Neubauer, Juergen; Berry, David A.

2010-01-01

Previous investigations using in vivo models to study the role of intrinsic laryngeal muscles in phonation have used neuromuscular stimulation to study voice parameters. However, these studies used coarse stimulation techniques using limited levels of neuromuscular stimulation. In the current investigation, a technique for fine control of laryngeal posturing was developed using graded stimulation of the laryngeal nerves. Vocal fold strain history to graded stimulation and a methodology for establishing symmetric laryngeal activation is presented. This methodology has immediate applications for the study of laryngeal paralysis and paresis, as well as general questions of neuromuscular control of the larynx. PMID:20369979

Myasthenia gravis: past, present, and future

PubMed Central

Conti-Fine, Bianca M.; Milani, Monica; Kaminski, Henry J.

2006-01-01

Myasthenia gravis (MG) is an autoimmune syndrome caused by the failure of neuromuscular transmission, which results from the binding of autoantibodies to proteins involved in signaling at the neuromuscular junction (NMJ). These proteins include the nicotinic AChR or, less frequently, a muscle-specific tyrosine kinase (MuSK) involved in AChR clustering. Much is known about the mechanisms that maintain self tolerance and modulate anti-AChR Ab synthesis, AChR clustering, and AChR function as well as those that cause neuromuscular transmission failure upon Ab binding. This insight has led to the development of improved diagnostic methods and to the design of specific immunosuppressive or immunomodulatory treatments. PMID:17080188

Neuromuscular ultrasound of cranial nerves.

PubMed

Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

2015-04-01

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

Protein kinase C isoforms at the neuromuscular junction: localization and specific roles in neurotransmission and development.

PubMed

Lanuza, Maria A; Santafe, Manel M; Garcia, Neus; Besalduch, Núria; Tomàs, Marta; Obis, Teresa; Priego, Mercedes; Nelson, Phillip G; Tomàs, Josep

2014-01-01

The protein kinase C family (PKC) regulates a variety of neural functions including neurotransmitter release. The selective activation of a wide range of PKC isoforms in different cells and domains is likely to contribute to the functional diversity of PKC phosphorylating activity. In this review, we describe the isoform localization, phosphorylation function, regulation and signalling of the PKC family at the neuromuscular junction. Data show the involvement of the PKC family in several important functions at the neuromuscular junction and in particular in the maturation of the synapse and the modulation of neurotransmission in the adult. © 2013 Anatomical Society.

Effect of mirror therapy and electrical stimulation on upper extremity function in stroke with hemiplegic patient: a pilot study.

PubMed

Paik, Young-Rim; Lee, Jeong-Hoon; Lee, Doo-Ho; Park, Hee-Su; Oh, Dong-Hwan

2017-12-01

[Purpose] This study investigated the effects of mirror therapy and neuromuscular electrical stimulation on upper extremity function in stroke patients. [Subjects and Methods] This study recruited 8 stroke patients. All patients were treated with mirror therapy and neuromuscular electrical stimulation five times per week for 4 weeks. Upper limb function evaluation was performed using upper extremity part of fugl meyer assessment. [Results] Before and after intervention, fugl meyer assessment showed significant improvement. [Conclusion] In this study, mirror therapy and neuromuscular electrical stimulation are effective methods for upper extremity function recovery in stroke patients.

Neuromuscular block after intra-arterially injected acetylcholine

PubMed Central

Pinelli, P.; Tonali, P.; Gambi, D.

1973-01-01

It has been suggested that the effect of ACTH in myasthenia gravis may be ascribed to an action involving neuromuscular transmission which favours repolarization processes, with a tendency towards hyperpolarization of the membranes of muscle fibres and motor nerve endings. A similar mechanism has been postulated for the action of ACTH in epilepsy (Klein, 1970). A direct or indirect action on nerve membrane would interfere with depolarization. There is evidence of raised concentration of intracellular potassium and increased outflow of sodium ions which would cause hyperpolarization of the membrane. This paper studies the effect of ACTH on the late block of neuromuscular transmission caused by acetylcholine (ACTH). Images PMID:4350704

The UK's National Programme for IT: Why was it dismantled?

PubMed

Justinia, Taghreed

2017-02-01

This paper discusses the UK's National Programme for IT (NPfIT), which was an ambitious programme launched in 2002 with an initial budget of some £6.2 billion. It attempted to implement a top-down digitization of healthcare in England's National Health Service (NHS). The core aim of the NPfIT was to bring the NHS' use of information technology into the 21st century, through the introduction of an integrated electronic patient record systems, and reforming the way that the NHS uses information, and hence to improve services and the quality of patient care. The initiative was not trusted by doctors and appeared to have no impact on patient safety. The project was marred by resistance due to the inappropriateness of a centralized authority making top-down decisions on behalf of local organizations. The NPfIT was officially dismantled in September 2011. Deemed the world's largest civil IT programme, its failure and ultimate demise sparked a lot of interest as to the reasons why. This paper summarises the underlying causes that lead to dismantling the NPfIT. At the forefront of those circumstances were the lack of adequate end user engagement, the absence of a phased change management approach, and underestimating the scale of the project.

Release and disposal of materials during decommissioning of Siemens MOX fuel fabrication plant at Hanau, Germany

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koenig, Werner; Baumann, Roland

2007-07-01

In September 2006, decommissioning and dismantling of the Siemens MOX Fuel Fabrication Plant in Hanau were completed. The process equipment and the fabrication buildings were completely decommissioned and dismantled. The other buildings were emptied in whole or in part, although they were not demolished. Overall, the decommissioning process produced approximately 8500 Mg of radioactive waste (including inactive matrix material); clearance measurements were also performed for approximately 5400 Mg of material covering a wide range of types. All the equipment in which nuclear fuels had been handled was disposed of as radioactive waste. The radioactive waste was conditioned on the basismore » of the requirements specified for the projected German final disposal site 'Schachtanlage Konrad'. During the pre-conditioning, familiar processes such as incineration, compacting and melting were used. It has been shown that on account of consistently applied activity containment (barrier concept) during operation and dismantling, there has been no significant unexpected contamination of the plant. Therefore almost all the materials that were not a priori destined for radioactive waste were released without restriction on the basis of the applicable legal regulations (chap. 29 of the Radiation Protection Ordinance), along with the buildings and the plant site. (authors)« less

The combined effect of dismantling for steam sterilization and aging on the accuracy of spring-style mechanical torque devices

PubMed Central

Mahshid, Minoo; Sadr, Seyed Jalil; Fayyaz, Ali; Kadkhodazadeh, Mahdi

2013-01-01

Purpose This study aimed to assess the combined effect of dismantling before sterilization and aging on the accuracy (±10% of the target torque) of spring-style mechanical torque devices (S-S MTDs). Methods Twenty new S-SMTDs from two different manufacturers (Nobel Biocare and Straumann: 10 of each type) were selected and divided into two groups, namely, case (group A) and control (group B). For sterilization, 100 cycles of autoclaving were performed in 100 sequences. In each sequence, 10 repetitions of peak torque values were registered for aging. To measure and assess the output of each device, a Tohnichi torque gauge was used (P<0.05). Results Before steam sterilization, all of the tested devices stayed within 10% of their target values. After 100 cycles of steam sterilization and aging with or without dismantling of the devices, the Nobel Biocare devices stayed within 10% of their target torque. In the Straumann devices, despite the significant difference between the peak torque and target torque values, the absolute error values stayed within 10% of their target torque. Conclusion Within the limitations of this study, there was no significant difference between the mean and absolute value of error between Nobel Biocare and Straumann S-S MTDs. PMID:24236244

Life cycle assessment of hybrid vehicles recycling: Comparison of three business lines of dismantling.

PubMed

Belboom, Sandra; Lewis, Grégory; Bareel, Pierre-François; Léonard, Angélique

2016-04-01

This paper undertakes an environmental evaluation of hybrid vehicles recycling, using industrial data from Comet Traitement SA in Belgium. Three business lines have been modelled and analysed. The first one is relative to the business as usual with a dismantling to recover batteries and engines followed by shredding and post shredding treatments. The second one considers, in addition, the removal of electronic control units (ECU) before shredding followed by same steps than in the first line and the last one is relative to the additional removal of big plastic parts before shredding and business as usual post shredding treatments. Results show non-significant environmental benefits when ECU or large parts of plastics are recovered before shredding. Improvements in terms of environmental benefits are lower than the uncertainty of the results. Indeed, the performing usual process for end-of-life vehicles (ELV) treatment reaches 97% of the ELV which is valorised in terms of metal and energy recoveries. Post shredding treatment units include metals, plastics and energy recovery of residues. Comet business as usual route for ELV valorisation is in accordance with the requirements of the European directive and recommendations for further improvement with dismantling of other parts (ECU or plastics) before shredding are non-relevant in this case. Copyright © 2016 Elsevier Ltd. All rights reserved.

Man-Machine Interface System for Neuromuscular Training and Evaluation Based on EMG and MMG Signals

PubMed Central

de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

2010-01-01

This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals. PMID:22163515

Man-machine interface system for neuromuscular training and evaluation based on EMG and MMG signals.

PubMed

de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

2010-01-01

This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals.

Is EMG of the lower leg dependent on weekly running mileage?

PubMed

Baur, H; Hirschmüller, A; Müller, S; Cassel, M; Mayer, F

2012-01-01

Neuromuscular activity of the lower leg is dependent on the task performed, speed of movement and gender. Whether training volume influences neuromuscular activity is not known. The EMG of physically active persons differing in running mileage was analysed to investigate this. 55 volunteers were allocated to a low (LM: < 30 km), intermediate (IM: > 30 km & < 45 km) or high mileage (HM: > 45 km) group according to their weekly running volume. Neuromuscular activity of the lower leg was measured during running (3.33 m·s - 1). Mean amplitude values for preactivation, weight acceptance and push-off were calculated and normalised to the mean activity of the entire gait cycle.Higher activity in the gastrocnemius group was observed in weight acceptance in LM compared to IM (+30%) and HM (+25%) but lower activity was present in the push-off for LM compared to IM and HM. For the peroneal muscle, differences were present in the push-off where HM showed increased activity compared to IM (+24%) and LM (+60%). The tibial muscle revealed slightly lower activity during preactivation for the high mileage runners. Neuromuscular activity differs during stance between the high and intermediate group compared to low mileage runners. Slight adaptations in neuromuscular activation indicate a more target-oriented activation strategy possibly due to repetitive training in runners with higher weekly mileage. © Georg Thieme Verlag KG Stuttgart · New York.

Exercise-induced dehydration does not alter time trial or neuromuscular performance.

PubMed

Stewart, C J; Whyte, D G; Cannon, J; Wickham, J; Marino, F E

2014-08-01

This study examined the effect of exercise-induced dehydration by ~4% body mass loss on 5-km cycling time trial (TT) performance and neuromuscular drive, independent of hyperthermia. 7 active males were dehydrated on 2 occasions, separated by 7 d. Participants remained dehydrated (DEH, -3.8±0.5%) or were rehydrated (REH, 0.2±0.6%) over 2 h before completing the TT at 18-25 °C, 20-30% relative humidity. Neuromuscular function was determined before dehydration and immediately prior the TT. The TT started at the same core temperature (DEH, 37.3±0.3°C; REH, 37.0±0.2 °C (P>0.05). Neither TT performance (DEH, 7.31±1.5 min; REH, 7.10±1.3 min (P>0.05)) or % voluntary activation were affected by dehydration (DEH, 88.7±6.4%; REH, 90.6±6.1% (P>0.05)). Quadriceps peak torque was significantly elevated in both trials prior to the TT (P<0.05), while a 19% increase in the rate of potentiated peak twitch torque development (P<0.05) was observed in the DEH trial only. All other neuromuscular measures were similar between trials. Short duration TT performance and neuromuscular function are not reduced by dehydration, independent of hyperthermia. © Georg Thieme Verlag KG Stuttgart · New York.

A meta-analysis of the effect of neuromuscular training on the prevention of the anterior cruciate ligament injury in female athletes.

PubMed

Yoo, Jae Ho; Lim, Bee Oh; Ha, Mina; Lee, Soo Won; Oh, Soo Jin; Lee, Yong Seuk; Kim, Jin Goo

2010-06-01

Female athletes are more prone to anterior cruciate ligament (ACL) injury than their male counterparts, presumably because of anatomical, hormonal, and neuromuscular differences. Of these three, only the neuromuscular component can be modified by preventive exercise. We aimed to evaluate the effect of a neuromuscular protocol on the prevention of ACL injury by performing meta-analysis, and to identify essential factors by subgroup analysis. An extensive literature review was conducted to identify relevant studies, and eventually, only seven randomized controlled trials or prospective cohort studies were included in the analysis. The odds ratios (OR) and the confidence interval (CI) for the overall effects of training and of potentially contributory factors were estimated. The OR and the 95% CI for the overall effect of the preventive training were 0.40 and [0.27, 0.60], respectively. Subgroup analysis revealed that an age under 18, soccer rather than handball, pre- and in-season training rather than either pre- or in-season training, and the plyometrics and strengthening components rather than balancing were significant. Meta-analysis showed that pre- and in-season neuromuscular training with an emphasis on plyometrics and strengthening exercises was effective at preventing ACL injury in female athletes, especially in those under 18 years of age. Further study is required to develop a relevant training program protocol of appropriate intensity.

Whole-body vibration does not influence knee joint neuromuscular function or proprioception.

PubMed

Hannah, R; Minshull, C; Folland, J P

2013-02-01

This study examined the acute effects of whole-body vibration (WBV) on knee joint position sense and indices of neuromuscular function, specifically strength, electromechanical delay and the rate of force development. Electromyography and electrically evoked contractions were used to investigate neural and contractile responses to WBV. Fourteen healthy males completed two treatment conditions on separate occasions: (1) 5 × 1 min of unilateral isometric squat exercise on a synchronous vibrating platform [30 Hz, 4 mm peak-to-peak amplitude] (WBV) and (2) a control condition (CON) of the same exercise without WBV. Knee joint position sense (joint angle replication task) and quadriceps neuromuscular function were assessed pre-, immediately-post and 1 h post-exercise. During maximum voluntary knee extensions, the peak force (PF(V)), electromechanical delay (EMD(V)), rate of force development (RFD(V)) and EMG of the quadriceps were measured. Twitch contractions of the knee extensors were electrically evoked to assess EMD(E) and RFD(E). The results showed no influence of WBV on knee joint position, EMD(V), PF(V) and RFD(V) during the initial 50, 100 or 150 ms of contraction. Similarly, electrically evoked neuromuscular function and neural activation remained unchanged following the vibration exercise. A single session of unilateral WBV did not influence any indices of thigh muscle neuromuscular performance or knee joint proprioception. © 2011 John Wiley & Sons A/S.

Joint angle affects volitional and magnetically-evoked neuromuscular performance differentially.

PubMed

Minshull, C; Rees, D; Gleeson, N P

2011-08-01

This study examined the volitional and magnetically-evoked neuromuscular performance of the quadriceps femoris at functional knee joint angles adjacent to full extension. Indices of volitional and magnetically-evoked neuromuscular performance (N=15 healthy males, 23.5 ± 2.9 years, 71.5 ± 5.4 kg, 176.5 ± 5.5 cm) were obtained at 25°, 35° and 45° of knee flexion. Results showed that volitional and magnetically-evoked peak force (PF(V) and P(T)F(E), respectively) and electromechanical delay (EMD(V) and EMD(E), respectively) were enhanced by increased knee flexion. However, greater relative improvements in volitional compared to evoked indices of neuromuscular performance were observed with increasing flexion from 25° to 45° (e.g. EMD(V), EMD(E): 36% vs. 11% improvement, respectively; F([2,14])=6.8, p<0.05). There were no significant correlations between EMD(V) and EMD(E) or PF(V) and P(T)F(E), at analogous joint positions. These findings suggest that the extent of the relative differential between volitional and evoked neuromuscular performance capabilities is joint angle-specific and not correlated with performance capabilities at adjacent angles, but tends to be smaller with increased flexion. As such, effective prediction of volitional from evoked performance capabilities at both analogous and adjacent knee joint positions would lack robustness. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neuromuscular activation patterns during treadmill walking after space flight

NASA Technical Reports Server (NTRS)

Layne, C. S.; McDonald, P. V.; Bloomberg, J. J.

1997-01-01

Astronauts adopt a variety of neuromuscular control strategies during space flight that are appropriate for locomoting in that unique environment, but are less than optimal upon return to Earth. We report here the first systematic investigation of potential adaptations in neuromuscular activity patterns associated with postflight locomotion. Astronaut-subjects were tasked with walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from their eyes after space flights of 8-15 days. Surface electromyography was collected from selected lower limb muscles and normalized with regard to mean amplitude and temporal relation to heel strike. In general, high correlations (more than 0.80) were found between preflight and postflight activation waveforms for each muscle and each subject: however relative activation amplitude around heel strike and toe off was changed as a result of flight. The level of muscle cocontraction and activation variability, and the relationship between the phasic characteristics of the ankle musculature in preparation for toe off also were altered by space flight. Subjects also reported oscillopsia during treadmill walking after flight. These findings indicate that, after space flight, the sensory-motor system can generate neuromuscular-activation strategies that permit treadmill walking, but subtle changes in lower-limb neuromuscular activation are present that may contribute to increased lower limb kinematic variability and oscillopsia also present during postflight walking.

Efficacy of brain-computer interface-driven neuromuscular electrical stimulation for chronic paresis after stroke.

PubMed

Mukaino, Masahiko; Ono, Takashi; Shindo, Keiichiro; Fujiwara, Toshiyuki; Ota, Tetsuo; Kimura, Akio; Liu, Meigen; Ushiba, Junichi

2014-04-01

Brain computer interface technology is of great interest to researchers as a potential therapeutic measure for people with severe neurological disorders. The aim of this study was to examine the efficacy of brain computer interface, by comparing conventional neuromuscular electrical stimulation and brain computer interface-driven neuromuscular electrical stimulation, using an A-B-A-B withdrawal single-subject design. A 38-year-old male with severe hemiplegia due to a putaminal haemorrhage participated in this study. The design involved 2 epochs. In epoch A, the patient attempted to open his fingers during the application of neuromuscular electrical stimulation, irrespective of his actual brain activity. In epoch B, neuromuscular electrical stimulation was applied only when a significant motor-related cortical potential was observed in the electroencephalogram. The subject initially showed diffuse functional magnetic resonance imaging activation and small electro-encephalogram responses while attempting finger movement. Epoch A was associated with few neurological or clinical signs of improvement. Epoch B, with a brain computer interface, was associated with marked lateralization of electroencephalogram (EEG) and blood oxygenation level dependent responses. Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was also prompted. Clinical improvement in upper-extremity function and muscle tone was observed. These results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.

Effectiveness of different exercises and stretching physiotherapy on pain and movement in patellofemoral pain syndrome: a randomized controlled trial.

PubMed

Moyano, F Revelles; Valenza, M C; Martin, L Martin; Caballero, Y Castellote; Gonzalez-Jimenez, E; Demet, G Valenza

2013-05-01

To compare the effectiveness of proprioceptive neuromuscular facilitation combined with exercise, classic stretching physiotherapy intervention, and educational intervention at improving patient function and pain in patients with patellofemoral pain syndrome. Randomized, controlled, blind trial over four months. Urban population, Spain. Patients undergoing primary care for retropatellar pain. Subjects were allocated on three different treatment options: a proprioceptive neuromuscular facilitation and aerobic exercise group, a classic stretching group, and a control treatment were applied over four months under the supervision of a physiotherapist. Knee Society Score, pain reported (Visual analogue scale) and knee range of motion. Assessments were completed at baseline and after four months. 74 patients were enrolled in the study and distributed between groups. Both the proprioceptive neuromuscular facilitation and classic stretching group showed significant changes in all variables after four months intervention (p < 0.001). The difference in mean Kujala knee score changes between groups (classic stretching group vs. proprioceptive neuromuscular facilitation group vs. control group) at four months was -24.05 (95% confidence interval (CI) -30.19, -17.90), p ≤ 0.001; vs. -39.03 (95% confidence interval (CI) -42.5, -35.5), p ≤ 0.001; vs. -0.238 (95% confidence interval (CI) -1.2, 0.726), p = 0.621, respectively. A proprioceptive neuromuscular facilitation intervention protocol combined with aerobic exercise showed a better outcome than a classic stretching protocol after four months.

Acute effect of scapular proprioceptive neuromuscular facilitation (PNF) techniques and classic exercises in adhesive capsulitis: a randomized controlled trial

PubMed Central

Balcı, Nilay Comuk; Yuruk, Zeliha Ozlem; Zeybek, Aslican; Gulsen, Mustafa; Tekindal, Mustafa Agah

2016-01-01

[Purpose] The aim of our study was to compare the initial effects of scapular proprioceptive neuromuscular facilitation techniques and classic exercise interventions with physiotherapy modalities on pain, scapular dyskinesis, range of motion, and function in adhesive capsulitis. [Subjects and Methods] Fifty-three subjects were allocated to 3 groups: scapular proprioceptive neuromuscular facilitation exercies and physiotherapy modalities, classic exercise and physiotherapy modalities, and only physiotherapy modalities. The intervention was applied in a single session. The Visual Analog Scale, Lateral Scapular Slide Test, range of motion and Simple Shoulder Test were evaluated before and just after the one-hour intervention in the same session (all in one session). [Results] All of the groups showed significant differences in shoulder flexion and abduction range of motion and Simple Shoulder Test scores. There were statistically significant differences in Visual Analog Scale scores in the proprioceptive neuromuscular facilitation and control groups, and no treatment method had significant effect on the Lateral Scapular Slide Test results. There were no statistically significant differences between the groups before and after the intervention. [Conclusion] Proprioceptive neuromuscular facilitation, classic exercise, and physiotherapy modalities had immediate effects on adhesive capsulitis in our study. However, there was no additional benefit of exercises in one session over physiotherapy modalities. Also, an effective treatment regimen for shoulder rehabilitation of adhesive capsulitis patients should include scapular exercises. PMID:27190456

Specialized neuromuscular training to improve neuromuscular function and biomechanics in a patient with quiescent juvenile rheumatoid arthritis.

PubMed

Myer, Gregory D; Brunner, Hermine I; Melson, Paula G; Paterno, Mark V; Ford, Kevin R; Hewett, Timothy E

2005-08-01

The purpose of this case report is to describe a novel multidisciplinary approach for evaluating and preparing a patient with quiescent juvenile rheumatoid arthritis (JRA) for safe sports participation. The patient was a 10-year-old girl with a history of bilateral knee arthritis who desired to participate in soccer and basketball. Range of motion and manual muscle testing of the lower extremity were within normal limits. Neuromuscular testing included kinematic and kinetic testing, isokinetic assessment, and postural stability testing. The patient's gait was near normal; however, she had narrowed step width and increased knee flexion at heel-strike. Landing analysis during a box drop vertical jump task showed increased and imbalanced (right versus left lower extremity) peak impact forces. The testing was followed by specialized neuromuscular training (SNT). Following SNT, heel-strike and step width were within normal limits, peak impact forces on the box drop test decreased by 31%, imbalance decreased by 46%, and vertical jump increased 15%. The isokinetic strength ratio between knee flexors and extensors and the overall balance measures were within normal limits and equal bilaterally. Patients with quiescent JRA may have abnormal biomechanics, which could place them at increased risk for injury or future articular cartilage damage. Specialized neuromuscular training may have helped to decrease the patient's risk for future injury or disease progression.

Mechanisms of inverse agonist action at D2 dopamine receptors

PubMed Central

Roberts, David J; Strange, Philip G

2005-01-01

Mechanisms of inverse agonist action at the D2(short) dopamine receptor have been examined. Discrimination of G-protein-coupled and -uncoupled forms of the receptor by inverse agonists was examined in competition ligand-binding studies versus the agonist [3H]NPA at a concentration labelling both G-protein-coupled and -uncoupled receptors. Competition of inverse agonists versus [3H]NPA gave data that were fitted best by a two-binding site model in the absence of GTP but by a one-binding site model in the presence of GTP. Ki values were derived from the competition data for binding of the inverse agonists to G-protein-uncoupled and -coupled receptors. Kcoupled and Kuncoupled were statistically different for the set of compounds tested (ANOVA) but the individual values were different in a post hoc test only for (+)-butaclamol. These observations were supported by simulations of these competition experiments according to the extended ternary complex model. Inverse agonist efficacy of the ligands was assessed from their ability to reduce agonist-independent [35S]GTPγS binding to varying degrees in concentration–response curves. Inverse agonism by (+)-butaclamol and spiperone occurred at higher potency when GDP was added to assays, whereas the potency of (−)-sulpiride was unaffected. These data show that some inverse agonists ((+)-butaclamol, spiperone) achieve inverse agonism by stabilising the uncoupled form of the receptor at the expense of the coupled form. For other compounds tested, we were unable to define the mechanism. PMID:15735658

eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation.

PubMed

Karbach, Susanne; Wenzel, Philip; Waisman, Ari; Munzel, Thomas; Daiber, Andreas

2014-01-01

Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the "kindling radical" hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. According to recent reports, vascular dysfunction in general and cardiovascular complications such as hypertension, atherosclerosis and coronary artery diseases may be connected to inflammatory processes. The present review is focusing on the uncoupling of endothelial nitric oxide synthase (eNOS) by different mechanisms involving so-called "redox switches". The oxidative depletion of tetrahydrobiopterin (BH4), oxidative disruption of the dimeric eNOS complex, S-glutathionylation and adverse phosphorylation as well as RONS-triggered increases in levels of asymmetric dimethylarginine (ADMA) will be discussed. But also new concepts of eNOS uncoupling and state of the art detection of this process will be described. Another part of this review article will address pharmaceutical interventions preventing or reversing eNOS uncoupling and thereby normalize vascular function in a given disease setting. We finally turn our attention to the inflammatory mechanisms that are also involved in the development of endothelial dysfunction and cardiovascular disease. Inflammatory cell and cytokine profiles as well as their interactions, which are among the kindling mechanisms for the development of vascular dysfunction will be discussed on the basis of the current literature.

Photophosphorylation capacity of stable spheroplast preparations of anabaena.

PubMed

Spiller, H

1980-09-01

Spheroplasts from Anabaena 7119 (formerly designated Nostoc muscorum) were prepared in the presence of serum albumin in 0.5 molar sucrose. Electron transport and photophosphorylation were preserved (> 70% of the maximum rate for 1 week). The pH profile of electron transport and photophosphorylation in the reactions H(2)O --> NADP, H(2)O --> methyl viologen, and H(2)O --> ferricyanide shows that uncoupling by ammonia is small throughout and increases slightly with higher pH. ADP + Pi increased NADP reduction from H(2)O by 2.5-fold. The ratios of ATP formed per electron pair transported ranged from 0.9 to 1.5. Effects of catalase and superoxide dismutase on the overall O(2) balance implicate pseudocyclic electron transport and phosphorylation. The quenching of 9-aminoacridine fluorescence indicates the formation of a Delta pH from 2 to 2.6 during illumination. This pH gradient is abolished by uncouplers; however, complete uncoupling is achieved only by 3-chlorocarbonyl cyanide phenylhydrazone or valinomycin + NH(4) (+). In the presence of NH(4) (+) alone, the membrane potential may act as the driving force for photophosphorylation.Increasing amounts of bovine serum albumin protected phosphorylation from uncoupling by silicomolybdic acid. 3-(3,4-Dichlorophenyl)-1, 1-dimethylurea-insensitive water oxidation by silicomolybdic acid provides evidence that the site for 3-(3,4-dichlorophenyl)-1, 1-dimethylurea action is on the acceptor and not donor side of photosystem II in the procaryote Anabaena. It is concluded that stable spheroplasts retain coupled electron transport approaching in vivo rates.

Dissipation of the Proton Electrochemical Potential in Intact Chloroplasts (II. The pH Gradient Monitored by Cytochrome f Reduction Kinetics).

PubMed Central

Nishio, J. N.; Whitmarsh, J.

1993-01-01

The potency of various uncouplers for collapsing the light-induced pH gradient across thylakoid membranes in intact chloroplasts was investigated by time-resolved optical spectroscopy. The thylakoid transmembrane pH gradient ([delta]pH) was monitored indirectly by measuring the rate of cytochrome (Cyt) f reduction following a light flash of sufficient duration to create a sizable [delta]pH. The results show that the rate of Cyt f reduction is controlled in part by the internal pH of the thylakoid inner aqueous space. At pH values from 6.5 to 8.0, the Cyt f reduction rate was maximal, whereas at lower pH values from 6.5 to 5.5 the reduction rate decreased to 25% of the maximal rate. The ability of three uncouplers, nigericin, carbonylcyanide m-chlorophenylhydrazone, and gramicidin, to accelerate the rate of Cyt f reduction was determined for intact chloroplasts isolated from spinach (Spinacia oleracea). The efficacy of the uncouplers for collapsing the [delta]pH was determined using the empirical relationship between the [delta]pH and the Cyt f reduction rate. For intact chloroplasts, nigericin was the most effective uncoupler, followed by carbonylcyanide m-chlorophenylhydrazone, which interacted strongly with bovine serum albumin. Gramicidin D, even at high gramicidin:chlorophyll ratios, did not completely collapse the pH gradient, probably because it partitions in the envelope membranes and does not enter the intact chloroplast. PMID:12231669

Polybrominated diphenyl ethers--plasma levels and thyroid status of workers at an electronic recycling facility.

PubMed

Julander, A; Karlsson, M; Hagström, K; Ohlson, C G; Engwall, M; Bryngelsson, I-L; Westberg, H; van Bavel, B

2005-08-01

Personnel working with electronic dismantling are exposed to polybrominated diphenyl ethers (PBDEs), which in animal studies have been shown to alter thyroid homeostasis. The aim of this longitudinal study was to measure plasma level of PBDEs in workers at an electronic recycling facility and to relate these to the workers' thyroid status. PBDEs and three thyroid hormones: triiodothyronine (T(3)), thyroxin (T(4)) and thyroid stimulating hormone (TSH) were repeatedly analysed in plasma from 11 workers during a period of 1.5 years. Plasma levels of PBDEs at start of employment were <0.5-9.1 pmol/g lipid weight (l.w.). The most common congener was PBDE #47 (median 2.8 pmol/g l.w.), followed by PBDE #153 (median 1.7 pmol/g l.w.), and PBDE #183 had a median value of <0.19 pmol/g l.w. After dismantling the corresponding median concentrations were: 3.7, 1.7 and 1.2 pmol/g l.w., respectively. These differences in PBDE levels were not statistically significant. PBDE #28 showed a statistically significantly higher concentration after dismantling than at start of employment (P=0.016), although at low concentrations (start 0.11 pmol/g l.w. and dismantling 0.26 pmol/g l.w.). All measured levels of thyroid hormones (T(3), T(4) and TSH) were within the normal physiological range. Statistically significant positive correlations were found between T(3) and #183 in a worker, between T(4) and both #28 and #100 in another worker and also between TSH and #99 and #154 in two workers. The workers' plasma levels of PBDEs fluctuated during the study period. Due to small changes in thyroid hormone levels it was concluded that no relevant changes were present in relation to PBDE exposure within the workers participating in this study.

End-of-Life in the railway sector: Analysis of recyclability and recoverability for different vehicle case studies.

PubMed

Delogu, Massimo; Del Pero, Francesco; Berzi, Lorenzo; Pierini, Marco; Bonaffini, Davide

2017-02-01

The railway system represents one of the most resource-efficient answer to our ever-growing demand for transport service and the development trends for the following years forecast a substantial increase in this sector. Considering the European Union, rolling stock realizes a significant share of both goods and passengers carriage while it is responsible for a derisory quota of environmental impact and energy consumption involved by transportation. Contrary to the low environmental impact, the amount of End-of-Life (EoL) waste generated by rolling stocks in relation to the number of vehicles is notable, much greater than in the case of road vehicles. As railway vehicles are constituted by many heterogeneous components, the EoL rolling stock is a precious source of materials, whose recycling brings measurable economic benefits and needs to be appropriately debated. The paper presents calculation of recoverability/recyclability rate for different typologies of vehicles representative of railway transport; calculation is performed on the basis of primary data and according to the recyclability and recoverability calculation method issued by UNIFE in the context of Product Category Rules (PCR). The typologies of railway vehicles taken into account are electric metro, diesel commuter train and high-speed electric train. The analysis envisages also to replicate the calculation in case innovative materials and manufacturing technologies are adopted in the construction of car-body structure. Results show that recyclability/recoverability rates are abundantly over the quota of 90% for each one of the three trains, these latter being made in major part of metals that benefit from very efficient recovery processes. The adoption of innovative materials and manufacturing technologies for car-body structure involves a scarce reduction of recyclability and recoverability rates (about 2% and 0.2% respectively) due to the introduction of components and materials characterized by critical dismantlability and low efficiency recovery processes; recoverability results less affected by lightweighting because post-shredding thermal recovery treatments are roughly independent with respect to dismantlability. A sensitivity analysis based on different dismantling scenarios reveals that the effectiveness of dismantling has a moderate influence on recyclability/recoverability rate (the variation does not exceed 3%). The low variability of recyclability/recoverability rate can be explained by the following reasons: predominance of metals in trains material composition, efficiency of metals separation processes close to 100%, post-shredding recycling processes of metals characterized by recovery factors equal to the ones of post-dismantling recycling processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharyngeal neuromuscular dysfunction associated with bilateral guttural pouch tympany in a foal

PubMed Central

Bell, Chris

2007-01-01

A 2-month-old warmblood filly was presented for a 1-week history of a large, nonpainful, fluctuant swelling of the parotid and laryngeal area. Bilateral guttural pouch tympany was diagnosed. Surgical correction resolved the guttural pouch tympany; however, postoperative pharyngeal neuromuscular dysfunction developed. PMID:17334035

Biochemistry of Neuromuscular Diseases: A Course for Undergraduate Students

ERIC Educational Resources Information Center

Ohlendieck, Kay

2002-01-01

This article outlines an undergraduate course focusing on supramolecular membrane protein complexes involved in the molecular pathogenesis of neuromuscular disorders. The emphasis of this course is to introduce students to the key elements involved in the ion regulation and membrane stabilization during muscle contraction and the role of these…

Chimney for enhancing flow of coolant water in natural circulation boiling water reactor

DOEpatents

Oosterkamp, Willem Jan; Marquino, Wayne

1999-01-05

A chimney which can be reconfigured or removed during refueling to allow vertical removal of the fuel assemblies. The chimney is designed to be collapsed or dismantled. Collapse or dismantlement of the chimney reduces the volume required for chimney storage during the refueling operation. Alternatively, the chimney has movable parts which allow reconfiguration of its structure. In a first configuration suitable for normal reactor operation, the chimney is radially constricted such that the chimney obstructs vertical removal of the fuel assemblies. In a second configuration suitable for refueling or maintenance of the fuel core, the parts of the chimney which obstruct access to the fuel assemblies are moved radially outward to positions whereat access to the fuel assemblies is not obstructed.

Neuromuscular fatigue in racquet sports.

PubMed

Girard, Olivier; Millet, Grégoire P

2008-02-01

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

Neuromuscular fatigue in racquet sports.

PubMed

Girard, Olivier; Millet, Grégoire P

2009-02-01

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

Feeding and Swallowing Disorders in Pediatric Neuromuscular Diseases: An Overview

PubMed Central

van den Engel-Hoek, Lenie; de Groot, Imelda J.M.; de Swart, Bert J.M.; Erasmus, Corrie E.

2015-01-01

Feeding and swallowing problems in infants and children have a great impact on health and wellbeing. The aim of this study was to provide an overview of recognized feeding and swallowing problems in different groups of children with neuromuscular diseases, based on relevant literature and expert opinion, and to propose recommendations for the assessment and treatment of these problems. Almost all pediatric neuromuscular diseases are accompanied by feeding and swallowing problems during the different phases of deglutition, problems that give rise to a wide variety of signs and symptoms, which emphasizes the importance of a comprehensive feeding and swallowing assessment by a speech and language therapist. PMID:27858755

Anti-GM2 gangliosides IgM paraprotein induces neuromuscular block without neuromuscular damage.

PubMed

Santafé, Manel M; Sabaté, M Mar; Garcia, Neus; Ortiz, Nico; Lanuza, M Angel; Tomàs, Josep

2008-11-15

We analyzed the effect on the mouse neuromuscular synapses of a human monoclonal IgM, which binds specifically to gangliosides with the common epitope [GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-]. We focused on the role of the complement. Evoked neurotransmission was partially blocked by IgM both acutely (1 h) and chronically (10 days). Transmission electron microscopy shows important nerve terminal growth and retraction remodelling though axonal injury can be ruled out. Synapses did not show mouse C5b-9 immunofluorescence and were only immunolabelled when human complement was added. Therefore, the IgM-induced synaptic changes occur without complement-mediated membrane attack.

Exercise and ankle sprain injuries: a comprehensive review.

PubMed

Calatayud, Joaquin; Borreani, Sebastien; Colado, Juan Carlos; Flandez, Jorge; Page, Phil; Andersen, Lars L

2014-02-01

Ankle sprains are common in team sports and sports played on courts, and often result in structural and functional alterations that lead to a greater reinjury risk. Specific exercises are often used to promote neuromuscular improvements in the prevention and rehabilitation of ankle injuries. This literature review summarizes the neuromuscular characteristics of common ankle sprains and the effectiveness of exercise as an intervention for improving neuromuscular function and preventing reinjury. Our review found that appropriate exercise prescription can increase static and dynamic balance and decrease injury recurrence. In particular, the addition of dynamic activities in the exercise program can be beneficial because of the anticipatory postural adjustments identified as a key factor in the injury mechanism.

Evidence-Based Systematic Review: Effects of Neuromuscular Electrical Stimulation on Swallowing and Neural Activation

ERIC Educational Resources Information Center

Clark, Heather; Lazarus, Cathy; Arvedson, Joan; Schooling, Tracy; Frymark, Tobi

2009-01-01

Purpose: To systematically review the literature examining the effects of neuromuscular electrical stimulation (NMES) on swallowing and neural activation. The review was conducted as part of a series examining the effects of oral motor exercises (OMEs) on speech, swallowing, and neural activation. Method: A systematic search was conducted to…

Proprioceptive Neuromuscular Facilitation Flexibility Techniques: Acute Effects on Arterial Blood Pressure.

ERIC Educational Resources Information Center

Cornelius, William L.; Craft-Hamm, Kelley

1988-01-01

The effects of stretching techniques on arterial blood pressure (ABP) were studied in three groups of 20 men each. Each group performed one of three proprioceptive neuromuscular facilitation (PNF) techniques. Results are presented. The study indicates that the benefits of stretching may outweigh the risk of elevated ABP. (JL)

Neuromuscular conditions for physicians - what you need to know.

PubMed

Edwards, Laura; Phillips, Margaret

2016-06-01

The Royal College of Physicians (RCP) and the British Society of Rehabilitation Medicine co-hosted a meeting entitled 'Neuromuscular conditions for physicians - what you need to know' at the RCP on 30 November 2015. There was a series of talks, ranging from in-depth genetic and molecular descriptions of pathology to multidisciplinary management of chronic neuromuscular conditions, which stimulated lively debate and discussion. Some overarching themes emerged from the day, most notably: i) the changing expectations and survival rates in Duchenne muscular dystrophy (DMD), which are transforming this disorder into an adult as much as a paediatric condition; ii) the need for integrated management and good communication -between services - whether primary, secondary and tertiary care, medical teams and intensivists, or the multiple teams involved in providing treatment to neuromuscular patients; and iii) in line with the above, the essential need for streamlining care such that patients can avoid spending most of their time attending outpatient appointments, and instead concentrate on living full lives and exploring educational, occupational, leisure and social opportunities. © 2016 Royal College of Physicians.

Children with central and peripheral neurologic disorders have distinguishable patterns of dysphagia on videofluoroscopic swallow study.

PubMed

van den Engel-Hoek, Lenie; Erasmus, Corrie E; van Hulst, Karen C M; Arvedson, Joan C; de Groot, Imelda J M; de Swart, Bert J M

2014-05-01

To determine whether findings on videofluoroscopic swallow studies reveal different patterns of dysphagia between children with central and peripheral neurologic disorders, a retrospective study of 118 videofluoroscopic swallow studies was completed. There were 3 groups: cerebral palsy with only spastic features (n = 53), cerebral palsy with dyskinetic features (n = 34), and neuromuscular disorders (myotonic dystrophy I, n = 5; spinal muscular atrophy I-II, n = 8; Duchenne muscular dystrophy, n = 8; other neuromuscular disorder, n = 10). Interpretation of the videofluoroscopic swallow studies was not blinded. The video fluoroscopic swallow study findings were compared dichotomously between the groups. Children with cerebral palsy demonstrated dysphagia in 1 or all phases of swallowing. In neuromuscular disorder, muscle weakness results in pharyngeal residue after swallow. The underlying swallowing problem in neuromuscular disorder is muscle weakness whereas that in cerebral palsy is more complex, having to do with abnormal control of swallowing. This study serves as a first exploration on specific characteristics of swallowing in different neurologic conditions and will help clinicians anticipate what they might expect.

[Inadvertent injection of succinylcholine as an epidural test dose].

PubMed

Pourzitaki, Chryssa; Tsaousi, Georgia; Logotheti, Helena; Amaniti, Ekaterini

Epidural action of neuromuscular blocking agents could be explained under the light of their physicochemical characteristics and epidural space properties. In the literature there are few cases of accidental neuromuscular agent's epidural administration, manifesting mainly with neuromuscular blockade institution or fasciculations. We report a case of accidental succinylcholine administration as an epidural test dose, in a female patient undergoing scheduled laparotomy, under combined general and epidural anesthesia. Approximately 2min after the succinylcholine injection the patient complained for shortness of breath, while mild fasciculations appeared in her trunk and face, managed by immediate general anesthesia institution. With the exception of a relatively longer duration of neuromuscular blockade compared with intravenous administration, no neurological or cardiovascular sequelae or other symptoms of local or systemic toxicity were observed. Oral administration of diazepam seems to lessen the adverse effects from accidental epidural administration of succinylcholine. The meticulous and discriminative labeling of syringes, as well as keeping persistent cautions during all anesthesia procedures remains of crucial importance. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Genomic and Proteomic Profiling Reveals Reduced Mitochondrial Function and Disruption of the Neuromuscular Junction Driving Rat Sarcopenia

PubMed Central

Ibebunjo, Chikwendu; Chick, Joel M.; Kendall, Tracee; Eash, John K.; Li, Christine; Zhang, Yunyu; Vickers, Chad; Wu, Zhidan; Clarke, Brian A.; Shi, Jun; Cruz, Joseph; Fournier, Brigitte; Brachat, Sophie; Gutzwiller, Sabine; Ma, QiCheng; Markovits, Judit; Broome, Michelle; Steinkrauss, Michelle; Skuba, Elizabeth; Galarneau, Jean-Rene; Gygi, Steven P.

2013-01-01

Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia. PMID:23109432

Physiological control of elaborate male courtship: Female choice for neuromuscular systems

PubMed Central

Fusani, Leonida; Barske, Julia; Day, Lainy D.; Fuxjager, Matthew J.; Schlinger, Barney A.

2015-01-01

Males of many animal species perform specialized courtship behaviours to gain copulations with females. Identifying physiological and anatomical specializations underlying performance of these behaviours helps clarify mechanisms through which sexual selection promotes the evolution of elaborate courtship. Our knowledge about neuromuscular specializations that support elaborate displays is limited to a few model species. In this review, we focus on the physiological control of the courtship of a tropical bird, the golden-collared manakin, which has been the focus of our research for nearly 20 years. Male manakins perform physically elaborate courtship displays that are quick, accurate and powerful. Females seem to choose males based on their motor skills suggesting that neuromuscular specializations possessed by these males are driven by female choice. Male courtship is activated by androgens and androgen receptors are expressed in qualitatively and quantitatively unconventional ways in manakin brain, spinal cord and skeletal muscles. We propose that in some species, females select males based on their neuromuscular capabilities and acquired skills and that elaborate steroid-dependent courtship displays evolve to signal these traits. PMID:25086380

Reversal of profound neuromuscular blockade with sugammadex in an infant after bronchial foreign body removal.

PubMed

Azizoglu, Mustafa; Birbicer, Handan; Memis, Suleyman; Taşkınlar, Hakan

2016-09-01

Sugammadex is a selective chemical agent that can reverse neuromuscular blockade induced by vecuronium and rocuronium. The aim of this report is to discuss the effectiveness of sugammadex in the reversal of neuromuscular blockade in children younger than 2 years. A 16-month-old boy, weighing 10 kg, was admitted to the pediatric emergency department due to choking, cyanosis, and severe respiratory distress that occurred while he was eating peanuts. In the emergency department, the patient's condition deteriorated, and he went into respiratory arrest. He was immediately intubated and taken to the operating room. A rigid bronchoscopy was performed under general anesthesia, with administration of intravenous pentothal (5 mg/kg), rocuronium (0.6 mg/kg), and fentanyl (0.5 μg/kg) in the operating room. The foreign body was removed within 6 minutes, and the profound neuromuscular blockade was reversed with a dose of 2 mg/kg sugammadex. He was extubated successfully after obtaining the spontaneous respiratory activity, and adequate breathing was restored. Clinical use of sugammadex in children younger than 2 years is not recommended because of the lack of clinical studies. In this case report, the profound neuromuscular blockade was successfully reversed with a dose of 2 mg/kg sugammadex in a 16-month-old boy. However, more prospective clinical studies are required for the safe use of this agent in children. Copyright © 2016 Elsevier Inc. All rights reserved.

Is there any relationship between orthotic usage and functional activities in children with neuromuscular disorders?

PubMed

Alemdaroğlu, İpek; Gür, Gozde; Bek, Nilgün; Yilmaz, Öznur T; Yakut, Yavuz; Uygur, Fatma; Karaduman, Ayşe

2014-02-01

Contractures of Achilles tendons and gastrocnemius muscle deteriorate the performance in daily living activities of patients with neuromuscular diseases. Ankle-foot orthoses help to prevent the progression of deformities and to obtain optimal position of the joints to support standing and walking. To investigate the relationship between orthotic usage and functional activities in pediatric patients with different neuromuscular diseases. Retrospective study. A total of 127 subjects' physical assessment forms were analyzed. Functional level, type of orthoses, falling frequencies, ankle joint range of motion, and timed performance tests were examined in two consecutive dates with an interval of 3 months. A total of 91 patients were using orthoses while 36 patients were not within assessment dates. A total of 64 of 91 (70.3%) patients were diagnosed with Duchenne muscular dystrophy. A total of 81 (89.0%) subjects were using plastic ankle-foot orthoses for positioning at nights and 10 (11%) were using different types of the orthoses (knee-ankle-foot orthoses, dynamic ankle-foot orthoses, and so on) for gait in the study group. Night ankle-foot orthoses were not found to be effective directly on functional performance in children with neuromuscular diseases, although they protect ankle from contractures and may help to correct gait and balance. This retrospective study shows that the positive effects of using an ankle-foot orthosis at night are not reflected in the functional performance of children with neuromuscular diseases. This may be due to the progressive deteriorating nature of the disease.

Anesthetic Considerations of Sporadic Inclusion Body Myositis in an Elderly Man With Orthopedic Trauma.

PubMed

Steck, Dominik T; Choi, Christine; Gollapudy, Suneeta; Pagel, Paul S

2016-04-01

Sporadic inclusion body myositis (IBM) is an inflammatory myopathy characterized by progressive asymmetric extremity weakness, oropharyngeal dysphagia, and the potential for exaggerated sensitivity to neuromuscular blockers and respiratory compromise. The authors describe their management of a patient with IBM undergoing urgent orthopedic surgery. An 81-year-old man with IBM suffered a left intertrochanteric femoral fracture after falling down stairs. His IBM caused progressive left proximal lower extremity, bilateral distal upper extremity weakness (left > right), and oropharyngeal dysphagia (solid food, pills). He denied dyspnea, exercise intolerance, and a history of aspiration. Because respiratory insufficiency resulting from diaphragmatic dysfunction and prolonged duration of action of neuromuscular blockers may occur in IBM, the authors avoided using a neuromuscular blocker. After applying cricoid pressure, anesthesia was induced using intravenous lidocaine, propofol, remifentanil followed by manual ventilation with inhaled sevoflurane in oxygen. Endotracheal intubation was accomplished without difficulty; anesthesia was then maintained using remifentanil and sevoflurane. The fracture was repaired with a trochanteric femoral nail. The patient was extubated without difficulty and made an uneventful recovery. In summary, there is a lack of consensus about the use of neuromuscular blockers in patients with IBM. The authors avoided these drugs and were able to easily secure the patient's airway and maintain adequate muscle relaxation using a balanced sevoflurane-remifentanil anesthetic. Clinical trials are necessary to define the pharmacology of neuromuscular blockers in patients with IBM and determine whether use of these drugs contributes to postoperative respiratory insufficiency in these vulnerable patients.

Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure

PubMed Central

Kimpinski, Kurt; Doherty, Timothy J.; Rice, Charles L.

2015-01-01

Diabetic polyneuropathy (DPN) can cause muscle atrophy, weakness, contractile slowing, and neuromuscular transmission instability. Our objective was to assess the response of the impaired neuromuscular system of DPN in humans when stressed with a sustained maximal voluntary contraction (MVC). Baseline MVC and evoked dorsiflexor contractile properties were assessed in DPN patients (n = 10) and controls (n = 10). Surface electromyography was used to record tibialis anterior evoked maximal compound muscle action potentials (CMAPs) and neuromuscular activity during MVCs. Participants performed a sustained isometric dorsiflexion MVC for which task termination was determined by the inability to sustain ≥60% MVC torque. The fatigue protocol was immediately followed by a maximal twitch, with additional maximal twitches and MVCs assessed at 30 s and 2 min postfatigue. DPN patients fatigued ∼21% more quickly than controls (P < 0.05) and featured less relative electromyographic activity during the first one-third of the fatigue protocol compared with controls (P < 0.05). Immediately following fatigue, maximal twitch torque was reduced similarly (∼20%) in both groups, and concurrently CMAPs were reduced (∼12%) in DPN patients, whereas they were unaffected in controls (P > 0.05). Twitch torque and CMAP amplitude recovered to baseline 30 s postfatigue. Additionally, at 30 s postfatigue, both groups had similar (∼10%) reductions in MVC torque relative to baseline, and MVC strength recovered by 2 min postfatigue. We conclude DPN patients possess less endurance than controls, and neuromuscular transmission failure may contribute to this greater fatigability. PMID:25663671

Effects of a single whole body cryotherapy (-110°C) bout on neuromuscular performance of the elbow flexors during isokinetic exercise.

PubMed

Ferreira-Junior, J B; Vieira, C A; Soares, S R S; Guedes, R; Rocha Junior, V A; Simoes, H G; Brown, L E; Bottaro, M

2014-12-01

It has been demonstrated that body cooling may decrease neuromuscular performance. However, the effect of a single session of whole body cryotherapy (-110°C) on neuromuscular performance has not been well documented. Thus, the aim of this study was to evaluate the effects of a single exposure of WBC on elbow flexor neuromuscular performance. Thirteen physically active, healthy young men (age=27.9±4.2 years, mass=79.4±9.7 kg, height=176.7±5.2 cm) were randomly exposed to 2 different experimental conditions separated by a minimum of 72 h: 1) whole body cryotherapy- 3 min at -110°C; 2) control- 3 min at 21°C. All subjects were tested for maximal isokinetic elbow flexion at 60°.s(-1) 30 min before and 10 min after each condition. There were no significant differences in peak torque, average power, total work or muscle activity between conditions. Peak torque was lower at post-test compared to pre-test in both conditions (F=6.58, p=0.025). However, there were no differences between pre-test and post-test for any other variables. These results indicate that strength specialists, athletic trainers and physical therapists might utilize whole body cryotherapy before training or rehabilitation without compromising neuromuscular performance of the elbow flexors. © Georg Thieme Verlag KG Stuttgart · New York.

A survey of the current use of neuromuscular blocking drugs among the Middle Eastern anesthesiologists.

PubMed

Eldawlatly, Abdelazeem; El-Tahan, Mohamed R

2013-04-01

This survey aimed to assess the extent of practice of the Middle Eastern anesthesiologists in the use of neuromuscular blocking agents (NMB) in 2012. We distributed an electronic survey among 577 members of the Triple-M Middle Eastern Yahoo anesthesia group, enquiring about their practice in the use of neuromuscular blocking agents. Questions concerned the routine first choice use of NMB, choice for tracheal intubation, the use of neuromuscular monitoring (NMT), type of NMB used in difficult airway, frequency of using suxamethonium, cisatracurium, rocuronium and sugammadex, observed side effects of rocuronium, residual curarization, and the reversal of residual curarization of rocuronium. A total of 71 responses from 22 Middle Eastern institutions were collected. Most of the Middle Eastern anesthesiologists were using cisatracurium and rocuronium frequently for tracheal intubation (39% and 35%, respectively). From the respondents, 2/3 were using suxamethonium for tracheal intubation in difficult airway, 1/3 were using rocuronium routinely and 17% have observed hypersensitivity reactions to rocuronium, 54% reported residual curarization from rocuronium, 78% were routinely using neostigmine to reverse the rocuronium, 21% used sugammadex occasionally, and 35% were using NMT routinely during the use of NMB. We believe that more could be done to increase the awareness of the Middle Eastern anesthesiologists about the high incidence of PROC (>20%) and the need for routine monitoring of neuromuscular function. This could be accomplished with by developing formal training programs and providing official guidelines.

Relationship between habitual physical activity and gross motor skills is multifaceted in 5- to 8-year-old children.

PubMed

Laukkanen, A; Pesola, A; Havu, M; Sääkslahti, A; Finni, T

2014-04-01

Adequate motor skills are essential for children participating in age-related physical activities, and gross motor skills may play an important role for maintaining sufficient level of physical activity (PA) during life course. The purpose of this study was to examine the relationship between gross motor skills and PA in children when PA was analyzed by both metabolic- and neuromuscular-based methods. Gross motor skills (KTK--Körperkoordinationstest für Kinder and APM inventory--manipulative skill test) of 84 children aged 5-8 years (53 preschoolers, 28 girls; 31 primary schoolers, 18 girls) were measured, and accelerometer-derived PA was analyzed using in parallel metabolic counts and neuromuscular impact methods. The gross motor skills were associated with moderate-to-high neuromuscular impacts, PA of vigorous metabolic intensity, and mean level of PA in primary school girls (0.5 < r < 0.7, P < 0.05), and with high impacts in preschool girls (0.3 < r < 0.5, P < 0.05). In preschool boys, moderate impacts, light-to-vigorous PA, and mean level of PA were associated with gross motor skills (0.4 < r < 0.7, P < 0.05). In conclusion, the result emphasizes an important relationship between gross motor skills and PA stressing both metabolic and neuromuscular systems in children. Furthermore, PA highly stressing neuromuscular system interacts with gross motor proficiency in girls especially. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Targeting NADPH oxidase decreases oxidative stress in the transgenic sickle cell mouse penis.

PubMed

Musicki, Biljana; Liu, Tongyun; Sezen, Sena F; Burnett, Arthur L

2012-08-01

Sickle cell disease (SCD) is a state of chronic vasculopathy characterized by endothelial dysfunction and increased oxidative stress, but the sources and mechanisms responsible for reactive oxygen species (ROS) production in the penis are unknown. We evaluated whether SCD activates NADPH oxidase, induces endothelial nitric oxide synthase (eNOS) uncoupling, and decreases antioxidants in the SCD mouse penis. We further tested the hypothesis that targeting NADPH oxidase decreases oxidative stress in the SCD mouse penis. SCD transgenic (sickle) mice were used as an animal model of SCD. Hemizygous (hemi) mice served as controls. Mice received an NADPH oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Penes were excised at baseline for molecular studies. Markers of oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NADPH oxidase subunits p67(phox) , p47(phox) , and gp91(phox) ), and enzymatic antioxidants (superoxide dismutase [SOD]1, SOD2, catalase, and glutathione peroxidase-1 [GPx1]) were measured by Western blot in penes. Sources of ROS, oxidative stress, and enzymatic antioxidants in the SCD penis. Relative to hemi mice, SCD increased (P<0.05) protein expression of NADPH oxidase subunits p67(phox) , p47(phox) , and gp91(phox) , 4-HNE-modified proteins, induced eNOS uncoupling, and reduced Gpx1 expression in the penis. Apocynin treatment of sickle mice reversed (P<0.05) the abnormalities in protein expressions of p47(phox) , gp91(phox) (but not p67(phox) ) and 4-HNE, but only slightly (P>0.05) prevented eNOS uncoupling in the penis. Apocynin treatment of hemi mice did not affect any of these parameters. NADPH oxidase and eNOS uncoupling are sources of oxidative stress in the SCD penis; decreased GPx1 further contributes to oxidative stress. Inhibition of NADPH oxidase upregulation decreases oxidative stress, implying a major role for NADPH oxidase as a ROS source and a potential target for improving vascular function in the SCD mouse penis. © 2012 International Society for Sexual Medicine.

Targeting NADPH Oxidase Decreases Oxidative Stress in the Transgenic Sickle Cell Mouse Penis

PubMed Central

Musicki, Biljana; Liu, Tongyun; Sezen, Sena F.; Burnett, Arthur L.

2012-01-01

Introduction Sickle cell disease (SCD) is a state of chronic vasculopathy characterized by endothelial dysfunction and increased oxidative stress, but the sources and mechanisms responsible for reactive oxygen species (ROS) production in the penis are unknown. Aims We evaluated whether SCD activates NADPH oxidase, induces endothelial nitric oxide synthase (eNOS) uncoupling, and decreases antioxidants in the SCD mouse penis. We further tested the hypothesis that targeting NADPH oxidase decreases oxidative stress in the SCD mouse penis. Methods SCD transgenic (sickle) mice were used as an animal model of SCD. Hemizygous (hemi) mice served as controls. Mice received an NADPH oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Penes were excised at baseline for molecular studies. Markers of oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NADPH oxidase subunits p67phox, p47phox, and gp91phox), and enzymatic antioxidants (superoxide dismutase [SOD]1, SOD2, catalase, and glutathione peroxidase-1 [GPx1]) were measured by Western blot in penes. Main Outcome Measures Sources of ROS, oxidative stress, and enzymatic antioxidants in the SCD penis. Results Relative to hemi mice, SCD increased (P < 0.05) protein expression of NADPH oxidase subunits p67phox, p47phox, and gp91phox, 4-HNE-modified proteins, induced eNOS uncoupling, and reduced Gpx1 expression in the penis. Apocynin treatment of sickle mice reversed (P < 0.05) the abnormalities in protein expressions of p47phox, gp91phox (but not p67phox) and 4-HNE, but only slightly (P > 0.05) prevented eNOS uncoupling in the penis. Apocynin treatment of hemi mice did not affect any of these parameters. Conclusion NADPH oxidase and eNOS uncoupling are sources of oxidative stress in the SCD penis; decreased GPx1 further contributes to oxidative stress. Inhibition of NADPH oxidase upregulation decreases oxidative stress, implying a major role for NADPH oxidase as a ROS source and a potential target for improving vascular function in the SCD mouse penis. PMID:22620981

Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urra, Félix A., E-mail: felix.urra@qf.uchile.cl; Córdova-Delgado, Miguel; Lapier, Michel

2016-01-15

Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cellmore » line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3{sub ADP}), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells. - Highlights: • Small changes on a hydroquinone scaffold modify the action on OXPHOS of cancer cells. • Complex I Inhibitors, uncoupler of OXPHOS and agents with dual action are described. • Cpd. 9 is an uncoupler agent of OXPHOS with selective anti-proliferative effects. • Useful information to design agents with a selective mechanism on OXPHOS is provided.« less

Simulation skill of APCC set of global climate models for Asian summer monsoon rainfall variability

NASA Astrophysics Data System (ADS)

Singh, U. K.; Singh, G. P.; Singh, Vikas

2015-04-01

The performance of 11 Asia-Pacific Economic Cooperation Climate Center (APCC) global climate models (coupled and uncoupled both) in simulating the seasonal summer (June-August) monsoon rainfall variability over Asia (especially over India and East Asia) has been evaluated in detail using hind-cast data (3 months advance) generated from APCC which provides the regional climate information product services based on multi-model ensemble dynamical seasonal prediction systems. The skill of each global climate model over Asia was tested separately in detail for the period of 21 years (1983-2003), and simulated Asian summer monsoon rainfall (ASMR) has been verified using various statistical measures for Indian and East Asian land masses separately. The analysis found a large variation in spatial ASMR simulated with uncoupled model compared to coupled models (like Predictive Ocean Atmosphere Model for Australia, National Centers for Environmental Prediction and Japan Meteorological Agency). The simulated ASMR in coupled model was closer to Climate Prediction Centre Merged Analysis of Precipitation (CMAP) compared to uncoupled models although the amount of ASMR was underestimated in both models. Analysis also found a high spread in simulated ASMR among the ensemble members (suggesting that the model's performance is highly dependent on its initial conditions). The correlation analysis between sea surface temperature (SST) and ASMR shows that that the coupled models are strongly associated with ASMR compared to the uncoupled models (suggesting that air-sea interaction is well cared in coupled models). The analysis of rainfall using various statistical measures suggests that the multi-model ensemble (MME) performed better compared to individual model and also separate study indicate that Indian and East Asian land masses are more useful compared to Asia monsoon rainfall as a whole. The results of various statistical measures like skill of multi-model ensemble, large spread among the ensemble members of individual model, strong teleconnection (correlation analysis) with SST, coefficient of variation, inter-annual variability, analysis of Taylor diagram, etc. suggest that there is a need to improve coupled model instead of uncoupled model for the development of a better dynamical seasonal forecast system.

Ammonia modifies enteric neuromuscular transmission through glial γ-aminobutyric acid signaling.

PubMed

Fried, David E; Watson, Ralph E; Robson, Simon C; Gulbransen, Brian D

2017-12-01

Impaired gut motility may contribute, at least in part, to the development of systemic hyperammonemia and systemic neurological disorders in inherited metabolic disorders, or in severe liver and renal disease. It is not known whether enteric neurotransmission regulates intestinal luminal and hence systemic ammonia levels by induced changes in motility. Here, we propose and test the hypothesis that ammonia acts through specific enteric circuits to influence gut motility. We tested our hypothesis by recording the effects of ammonia on neuromuscular transmission in tissue samples from mice, pigs, and humans and investigated specific mechanisms using novel mutant mice, selective drugs, cellular imaging, and enzyme-linked immunosorbent assays. Exogenous ammonia increased neurogenic contractions and decreased neurogenic relaxations in segments of mouse, pig, and human intestine. Enteric glial cells responded to ammonia with intracellular Ca 2+ responses. Inhibition of glutamine synthetase and the deletion of glial connexin-43 channels in hGFAP :: Cre ER T2+/- /connexin43 f/f mice potentiated the effects of ammonia on neuromuscular transmission. The effects of ammonia on neuromuscular transmission were blocked by GABA A receptor antagonists, and ammonia drove substantive GABA release as did the selective pharmacological activation of enteric glia in GFAP::hM3Dq transgenic mice. We propose a novel mechanism whereby local ammonia is operational through GABAergic glial signaling to influence enteric neuromuscular circuits that regulate intestinal motility. Therapeutic manipulation of these mechanisms may benefit a number of neurological, hepatic, and renal disorders manifesting hyperammonemia. NEW & NOTEWORTHY We propose that local circuits in the enteric nervous system sense and regulate intestinal ammonia. We show that ammonia modifies enteric neuromuscular transmission to increase motility in human, pig, and mouse intestine model systems. The mechanisms underlying the effects of ammonia on enteric neurotransmission include GABAergic pathways that are regulated by enteric glial cells. Our new data suggest that myenteric glial cells sense local ammonia and directly modify neurotransmission by releasing GABA. Copyright © 2017 the American Physiological Society.

Effects of an 8-Week Body-Weight Neuromuscular Training on Dynamic Balance and Vertical Jump Performances in Elite Junior Skiing Athletes: A Randomized Controlled Trial.

PubMed

Vitale, Jacopo A; La Torre, Antonio; Banfi, Giuseppe; Bonato, Matteo

2018-04-01

Vitale, JA, La Torre, A, Banfi, G, and Bonato, M. Effects of an 8-week body-weight neuromuscular training on dynamic balance and vertical jump performances in elite junior skiing athletes: a randomized controlled trial. J Strength Cond Res 32(4): 911-920, 2018-The aim of the present randomized controlled trial was to evaluate the effects of an 8-week neuromuscular training program focused on core stability, plyometric, and body-weight strengthening exercises on dynamic postural control and vertical jump performance in elite junior skiers. Twenty-four Italian elite junior male skiers were recruited and randomized to either an experimental group (EG), performing neuromuscular warm-up exercises, (EG; n = 12; age 18 ± 1 years; body mass 66 ± 21 kg; height 1.70 ± 0.1 m) or a control group (CG) involved in a standard warm-up (CG; n = 12; age 18 ± 1 years; body mass 62 ± 14 kg; height 1.73 ± 0.1 m). lower quarter Y-Balance Test (YBT), countermovement jump (CMJ), and drop jump (DJ) at baseline (PRE) and at the end (POST) of the experimental procedures were performed. No significant differences between EG and CG were observed at baseline. Results showed that EG achieved positive effects from PRE to POST measures in the anterior, posteromedial, posterolateral directions, and composite score of YBT for both lower limbs, whereas no significant differences were detected for CG. Furthermore, 2-way analysis of variance with Bonferroni's multiple comparisons test did not reveal any significant differences in CMJ and DJ for both EG and CG. The inclusion of an 8-week neuromuscular warm-up program led to positive effects in dynamic balance ability but not in vertical jump performance in elite junior skiers. Neuromuscular training may be an effective intervention to specifically increase lower limb joint awareness and postural control.

The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm

PubMed Central

Kim, Seung Soo; Chung, Chan Jong; Lee, Seung-Cheol

2011-01-01

Background Neostigmine augments clindamycin-induced neuromuscular block and antagonizes rocuronium-induced neuromuscular block; however, it remains unclear whether neostigmine enhances the neuromuscular blocking (NMB) that is caused by combinations of rocuronium and clindamycin. The intent of this study was to determine whether neostigmine potentiates the muscle relaxation that is induced by combinations of rocuronium and clindamycin and to estimate whether both clindamycin and rocuronium have synergistic actions on NMB. Methods Forty-one left phrenic nerve-hemidiaphragms (from male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Three consecutive single twitches (ST, 0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained for each increase in concentration of rocuronium or clindamycin. The concentrations of rocuronium were cumulatively increased until an 80% to 90% reduction in ST was attained in the Krebs solutions pre-treated with 0 (n = 5), 0.1 (n = 1), 0.25 (n = 1), 0.5 (n = 4), or 1.0 (n = 1) mM clindamycin or with 0 (n = 4), 0.1 (n = 1), 0.5 (n = 5), 1.0 (n = 5), or 2.0 (n = 4) mM clindamycin in combination with 250 nM neostigmine, and so were the concentrations of clindamycin in the Krebs solutions pre-treated with 0 (n = 6) or 250 nM (n = 6) neostigmine. Results Clindamycin increased the potency of rocuronium for ST and tetanic fade, irrespective of the presence of neostigmine. Neostigmine shifted the concentration-response curve of rocuronium to the right in the presence or absence of clindamycin. The interaction between rocuronium and clindamycin was synergistic when clindamycin concentrations were in excess of 0.5 mM, irrespective of the presence of neostigmine. Conclusions Neostigmine may partially antagonize the neuromuscular block that is induced by a combination of clindamycin and rocuronium. Clinicians are advised to be aware that clindamycin synergistically increases the degree of rocuronium-induced neuromuscular block, even when neostigmine is present. PMID:22110886

Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)†,.

PubMed

Kaufhold, N; Schaller, S J; Stäuble, C G; Baumüller, E; Ulm, K; Blobner, M; Fink, H

2016-02-01

The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block, that is, a train-of-four ratio (TOFR) ≥0.2. Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1) i.v. for tracheal intubation and, if necessary, incremental doses of 0.1-0.2 mg kg(-1). Neuromuscular monitoring was performed by calibrated electromyography. Once the TOFR recovered to 0.2, patients were randomized to receive sugammadex (0.25, 0.5, 0.75, 1.0, or 1.25 mg kg(-1) i.v.), neostigmine (10, 25, 40, 55, or 70 µg kg(-1) i.v.), or saline (n=9 per group). Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95% of patients, respectively. Neostigmine was not able to fulfil the end points. Based on the best-fitting model, the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95% of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1), respectively. A residual neuromuscular block of a TOFR of 0.2 cannot be reversed reliably with neostigmine within 10 min. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2. NCT01006720. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuromuscular performance in the hip joint of elderly fallers and non-fallers.

PubMed

Morcelli, Mary Hellen; LaRoche, Dain Patrick; Crozara, Luciano Fernandes; Marques, Nise Ribeiro; Hallal, Camilla Zamfolini; Rossi, Denise Martineli; Gonçalves, Mauro; Navega, Marcelo Tavella

2016-06-01

Low strength and neuromuscular activation of the lower limbs have been associated with falls making it an important predictor of functional status in the elderly. To compare the rate of neuromuscular activation, rate of torque development, peak torque and reaction time between young and elderly fallers and non-fallers for hip flexion and extension. We evaluated 44 elderly people who were divided into two groups: elderly fallers (n = 20) and elderly non-fallers (n = 24); and 18 young people. The subjects performed three isometric hip flexion and extension contractions. Electromyography data were collected for the rectus femoris, gluteus maximus and biceps femoris muscles. The elderly had 49 % lower peak torque and 68 % lower rate of torque development for hip extension, 28 % lower rate of neuromuscular activation for gluteus maximus and 38 % lower rate of neuromuscular activation for biceps femoris than the young (p < 0.05). Furthermore, the elderly had 42 % lower peak torque and 62 % lower rate of torque development for hip flexion and 48 % lower rate of neuromuscular for rectus femoris than the young (p < 0.05). The elderly fallers showed consistent trend toward a lower rate of torque development than elderly non-fallers for hip extension at 50 ms (29 %, p = 0.298, d = 0.76) and 100 ms (26 %, p = 0.452, d = 0.68).The motor time was 30 % slower for gluteus maximus, 42 % slower for rectus femoris and 50 % slower for biceps femoris in the elderly than in the young. Impaired capacity of the elderly, especially fallers, may be explained by neural and morphological aspects of the muscles. The process of senescence affects the muscle function of the hip flexion and extension, and falls may be related to lower rate of torque development and slower motor time of biceps femoris.

Outcomes and complications of S2 alar iliac fixation technique in patients with neuromuscular scoliosis: experience in a third level pediatric hospital.

PubMed

Montero, Carlos Segundo; Meneses, David Alberto; Alvarado, Fernando; Godoy, Wilmer; Rosero, Diana Isabel; Ruiz, Jose Manuel

2017-12-01

Multiple techniques are utilized for distal fixation in patients with neuromuscular scoliosis. Although there is evidence of benefit with S2 alar iliac (S2AI) fixation, this remains controversial. The objective of this study is to evaluate the radiological outcomes and complications associated with this surgical technique in a pediatric population. An observational retrospective case series study was performed. All pediatric patients between January 2011 and February 2014 diagnosed with neuromuscular scoliosis associated with pelvic obliquity, which required surgery with fixation unto S2AI, were included. Clinical, radiological findings, and adverse events were presented with measures of central tendency. Comparison of deformity correction was carried out using a non-parametric analysis for related samples (Wilcoxon signed-rank test). Significance was set at P<0.05. A total of 31 patients diagnosed with neuromuscular scoliosis that met inclusion criteria were analyzed. The leading cause of neuromuscular scoliosis in 23 (74.2%) patients was spastic cerebral palsy (CP). The correction of pelvic obliquity in the immediate postoperative period was of 76%, which is statistically significant. The extent of correction that patients maintained at the end of the follow-up was analyzed, and it was found that there were no significant differences in this magnitude, compared with the immediate postoperative pelvic obliquity. The mean follow-up time was 9±7 months. Regarding postoperative adverse events, occurred in 64.5% of patients, the most common outcome was pneumonia (14.8%). The overall rate of complications related to instrumentation was low (1.9%), which corresponds to one patient with an intra-articular screw in the left hip that required repositioning. S2AI fixation for the treatment of neuromuscular scoliosis is a safe alternative, in which the onset of adverse events is related to the comorbidities of patients instead of the surgical procedure itself. An approximate correction of 76% of pelvic obliquity is maintained during the follow-up.

A comparison of hamstring muscle activity during different screening tests for non-contact ACL injury.

PubMed

Husted, Rasmus S; Bencke, Jesper; Andersen, Lars L; Myklebust, Grethe; Kallemose, Thomas; Lauridsen, Hanne B; Hölmich, Per; Aagaard, Per; Zebis, Mette K

2016-06-01

Reduced ability to activate the medial hamstring muscles during a sports-specific sidecutting movement has been found to be a potential risk factor for non-contact ACL injury. However, whether a reduced ability to activate the medial hamstring muscle is a general neuromuscular phenomenon and thereby observable independently of the type of clinical screening tests used is not known. This cross sectional study investigated the rank correlation of knee joint neuromuscular activity between three different ACL injury risk screening tests. Sixty-two adolescent female elite football and handball players (16.7±1.3years) participated in the study. Using surface electromyography (EMG) assessment, the neuromuscular activity of medial hamstring muscle (semitendinosus, ST), lateral hamstring muscle (biceps femoris, BF) and quadriceps muscle (vastus lateralis, VL) were monitored during three standardized screening tests - i.e. one-legged horizontal hop (OLH), drop vertical jump (DJ) and sidecutting (SC). Neuromuscular pre-activity was measured in the time interval 10ms prior to initial contact on a force plate. For neuromuscular hamstring muscle pre-activity, correlation analysis (Spearman correlation coefficient) showed low-to-moderate correlations between SC and 1) DJ (rs=0.34-0.36, P<0.05) and 2) OLH (rs=0.40-0.41, P<0.05), respectively. In conclusion, the present data suggest that hamstring pre-activity share some common variance during the examined tests. However, a lack of strong correlation suggests that we cannot generalize one risk factor during one test to another test. The present data demonstrate that one-legged horizontal hop and drop vertical jump testing that are commonly used in the clinical setting does not resemble the specific neuromuscular activity patterns known to exist during sidecutting, a well known high risk movement for non-contact ACL injury. Copyright © 2016 Elsevier B.V. All rights reserved.

Reliability and validity of the Chinese version of the Pediatric Quality Of Life InventoryTM (PedsQLTM) 3.0 neuromuscular module in children with Duchenne muscular dystrophy.

PubMed

Hu, Jun; Jiang, Li; Hong, Siqi; Cheng, Li; Kong, Min; Ye, Yuanzhen

2013-03-15

The Pediatric Quality of Life Inventory(TM) (PedsQL(TM)) is a widely used instrument to measure pediatric health-related quality of life (HRQOL) in children aged 2 to 18 years. The current study aimed to evaluate the reliability and validity of the Chinese version of the PedsQL(TM) 3.0 Neuromuscular Module in children with Duchenne muscular dystrophy (DMD). The PedsQL(TM) 3.0 Neuromuscular Module was translated into Chinese following PedsQL(TM) Measurement Model Translation Methodology. The Chinese version scale was administered to 56 children with DMD and their parents, and the psychometric properties were evaluated. The missing value percentages for each item of the Chinese version scale ranged from 0.00% to 0.54%. Internal consistency reliability approached or exceeded the minimum reliability standard of α = 0.7 (child α = 0.81, parent α = 0.86). Test-retest reliability was satisfactory, with intraclass correlation coefficients (ICCs) of 0.66 for children and 0.88 for parents (P < 0.01). Correlation coefficients between iteims and their hypothesized subscales were higher than those with other subscales (P < 0.05). The subscale of "About My/My Child's Neuromuscular Disease" significantly related to mobility and stair climbing status (Child t = 2.21, Parent t = 2.83, P < 0.05). The inter-correlations among the Chinese version of the PedsQL(TM) 3.0 Neuromuscular Module and the PedsQL(TM) 4.0 Generic Core Scales had medium to large effect sizes (P < 0.05). The child self-report scores were in moderate agreement with the parent proxy-report scores (ICC = 0.51, P < 0.05). The Chinese version of the PedsQLTM 3.0 Neuromuscular Module has acceptable psychometric properties. It is a reliable measure of disease-specific HRQOL in Chinese children with DMD.

Neuromuscular electrical stimulation and the treatment of lower urinary tract dysfunction in multiple sclerosis--a double blind, placebo controlled, randomised clinical trial.

PubMed

McClurg, D; Ashe, R G; Lowe-Strong, A S

2008-01-01

Lower urinary tract dysfunction affects up to 75% of the multiple sclerosis population. Results from our recent Pilot Study (McClurg et al., 2006) indicated that a combined programme of pelvic floor muscle training, electromyography biofeedback and neuromuscular electrical stimulation modalities may alleviate some of the distressing symptoms within this population. This clinical trial aimed to evaluate further the efficacy of these interventions and to establish the benefit of neuromuscular electrical stimulation above and beyond that of EMG biofeedback and pelvic floor muscle training. 74 multiple sclerosis patients who presented with lower urinary tract dysfunction were randomly allocated to one of two groups - Group 1 received Pelvic Floor Muscle Training, Electromyography Biofeedback and Placebo Neuromuscular Electrical Stimulation (n=37), and Group 2 which received Pelvic Floor Muscle Training, Electromyography Biofeedback, and Active Neuromuscular Electrical Stimulation (n=37). Treatment was for nine weeks with outcome measures recorded at weeks 0, 9, 16 and 24. The Primary Outcome Measure was the number of leakage episodes. Within group analysis was by Paired Samples t-test. Group differences were analysed using Repeated Measures Analysis of Variance and Post-hoc tests were used to determine the significance of differences between Groups at each time point. The mean number of incontinence episodes were reduced in Group 2 by 85% (p=0.001) whereas in Group 1 a lesser reduction of 47% (p=0.001) was observed. However, there was a statistically superior benefit in Group 2 when compared to Group 1 (p=0.0028). This superior benefit was evident in all other outcome measures. The addition of Active Neuromuscular Electrical Stimulation to a programme of Pelvic Floor Muscle Training and Electromyography Biofeedback should be considered as a first-line option in alleviating some of the symptoms of lower urinary tract dysfunction associated with multiple sclerosis. (c) 2007 Wiley-Liss, Inc.