Sample records for hindlimb unloading increases

  1. Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions (United States)

    Aviles, Hernan; Belay, Tesfaye; Fountain, Kimberly; Vance, Monique; Sonnenfeld, Gerald


    It has been reported that spaceflight conditions alter the immune system and resistance to infection [Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 170: 262-268, 2002; Hankins WR and Ziegelschmid JF. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 43-81. (NASA Spec. Rep. SP-368)]. Ground-based models, including the hindlimb-unloading model, have become important tools for increasing understanding of how spaceflight conditions can influence physiology. The objective of the present study was to determine the effect of hindlimb unloading on the susceptibility of mice to Pseudomonas aeruginosa infection. Hindlimb-unloaded and control mice were subcutaneously infected with 1 LD50 of P. aeruginosa. Survival, bacterial organ load, and antibody and corticosterone levels were compared among the groups. Hindlimb unloading had detrimental effects for infected mice. Animals in the hindlimb-unloaded group, compared with controls, 1). showed significantly increased mortality and reduced time to death, 2). had increased levels of corticosterone, and 3). were much less able to clear bacteria from the organs. These results suggest that hindlimb unloading may induce the production of corticosterone, which may play a critical role in the modulation of the immune system leading to increased susceptibility to P. aeruginosa infection.

  2. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats (United States)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.


    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  3. Hindlimb unloading results in increased predisposition to cardiac arrhythmias and alters left ventricular connexin 43 expression. (United States)

    Moffitt, Julia A; Henry, Matthew K; Welliver, Kathryn C; Jepson, Amanda J; Garnett, Emily R


    Hindlimb unloading (HU) is a well-established animal model of cardiovascular deconditioning. Previous data indicate that HU results in cardiac sympathovagal imbalance. It is well established that cardiac sympathovagal imbalance increases the risk for developing cardiac arrhythmias. The cardiac gap junction protein connexin 43 (Cx43) is predominately expressed in the left ventricle (LV) and ensures efficient cell-to-cell electrical coupling. In the current study we wanted to test the hypothesis that HU would result in increased predisposition to cardiac arrhythmias and alter the expression and/or phosphorylation of LV-Cx43. Electrocardiographic data using implantable telemetry were obtained over a 10- to 14-day HU or casted control (CC) condition and in response to a sympathetic stressor using isoproterenol administration and brief restraint. The arrhythmic burden was calculated using a modified scoring system to quantify spontaneous and provoked arrhythmias. In addition, Western blot analysis was used to measure LV-Cx43 expression in lysates probed with antibodies directed against the total and an unphosphorylated form of Cx43 in CC and HU rats. HU resulted in a significantly greater total arrhythmic burden during the sympathetic stressor with significantly more ventricular arrhythmias occurring. In addition, there was increased expression of total LV-Cx43 observed with no difference in the expression of unphosphorylated LV-Cx43. Specifically, the increased expression of LV-Cx43 was consistent with the phosphorylated form. These data taken together indicate that cardiovascular deconditioning produced through HU results in increased predisposition to cardiac arrhythmias and increased expression of phosphorylated LV-Cx43.

  4. Effects of hindlimb unloading on neuromuscular development of neonatal rats (United States)

    Huckstorf, B. L.; Slocum, G. R.; Bain, J. L.; Reiser, P. M.; Sedlak, F. R.; Wong-Riley, M. T.; Riley, D. A.


    We hypothesized that hindlimb suspension unloading of 8-day-old neonatal rats would disrupt the normal development of muscle fiber types and the motor innervation of the antigravity (weightbearing) soleus muscles but not extensor digitorum longus (EDL) muscles. Five rats were suspended 4.5 h and returned 1.5 h to the dam for nursing on a 24 h cycle for 9 days. To control for isolation from the dam, the remaining five littermates were removed on the same schedule but not suspended. Another litter of 10 rats housed in the same room provided a vivarium control. Fibers were typed by myofibrillar ATPase histochemistry and immunostaining for embryonic, slow, fast IIA and fast IIB isomyosins. The percentage of multiple innervation and the complexity of singly-innervated motor terminal endings were assessed in silver/cholinesterase stained sections. Unique to the soleus, unloading accelerated production of fast IIA myosin, delayed expression of slow myosin and retarded increases in standardized muscle weight and fiber size. Loss of multiple innervation was not delayed. However, fewer than normal motor nerve endings achieved complexity. Suspended rats continued unloaded hindlimb movements. These findings suggest that motor neurons resolve multiple innervation through nerve impulse activity, whereas the postsynaptic element (muscle fiber) controls endplate size, which regulates motor terminal arborization. Unexpectedly, in the EDL of unloaded rats, transition from embryonic to fast myosin expression was retarded. Suspension-related foot drop, which stretches and chronically loads EDL, may have prevented fast fiber differentiation. These results demonstrate that neuromuscular development of both weightbearing and non-weightbearing muscles in rats is dependent upon and modulated by hindlimb loading.

  5. Calcium balance in mature male rats with unloaded hindlimbs (United States)

    Navidi, Meena; Evans, Juliann; Wolinsky, Ira; Arnaud, Sara B.


    BACKGROUND: Calcium balances, regulated by the calcium endocrine system, are negative during spaceflight but have not been reported in flight simulation models using fully mature small animals. METHODS: We conducted two calcium (Ca) balance studies in 6-mo-old male rats exposed to a model that unloads the hindlimbs (HU) for 4 wk. Control (C) and HU rats were fed diets with 0.5% Ca in the first and 0.1% Ca in the second study. Housing in metabolic cages enabled daily food and water intake measurements as well as collections of urine and fecal specimens. At necropsy, blood was obtained for measures of Ca-regulating hormones. RESULTS: Both C and HU rats adjusted to housing and diets with decreases in body weight and negative Ca balances during the first week of each experiment. Thereafter, averages of Ca balances were more negative in the unloaded rats than controls: -8.1 vs. -1.6 mg x d(-1) in rats fed 0.5% (p Parathyroid hormone (PTH) was suppressed and 1,25-D increased in HU rats fed 0.5% Ca. C rats fed 0.1% Ca had increased PTH and 1,25-D was the same as in the HU group. CONCLUSION: After adaptation, Ca balances were more negative in mature male rats with unloaded hindlimbs than controls, an effect from increased secretion and loss of endogenous fecal Ca associated with increased 1,25-D in Ca-replete and Ca-restricted rats.

  6. Deoxypyridinoline in the Urine of Rats with Unloaded Hindlimbs (United States)

    Arnaud, Sara B.; Navidi, M.; Wren, J.; Holton, Emily M. (Technical Monitor)


    The urinary excretion of deoxypyridinoline (U-Dpd), a nonreducible collagen crosslink in bone released by osteoclastic activity, is thought to be an accurate marker of bone resorption. The role of increased resorption in the osteopenia of a space flight model which unloads the hindlimbs by suspending the tail is controversial. To assess skeletal resorption in the model we measured U-Dpd (Pyrilinks-D, Metro Biosystems, Inc.) in serial 24 hour urine specimens collected from 250 a (Y) and 450 a (M) male rats with unloaded hindlimbs for four weeks. Both groups of rats were fed AIN76 diets with calcium restricted to 0.2% in Y and to 0.1 % in M. Blood was obtained after 28 days for parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25-D) and alkaline phosphatase (Alkptase). Basal U-Dpd was higher and more variable in Y than M (475+/-200 vs 67+/-9, nM/mM creatinine, panimals exposed to the space flight model, 2 situations with opposite effects on bone resorption.

  7. Effects of the hindlimb-unloading model of spaceflight conditions on resistance of mice to infection with Klebsiella pneumoniae (United States)

    Belay, Tesfaye; Aviles, Hernan; Vance, Monique; Fountain, Kimberly; Sonnenfeld, Gerald


    BACKGROUND: It has been well documented in several studies that many immunologic parameters are altered in experimental animals and human subjects who have flown in space. However, it is not fully known whether these immunologic changes could result in increased susceptibility to infection. Hindlimb (antiorthostatic) unloading of rodents has been used successfully to simulate some of the effects of spaceflight on physiologic systems. OBJECTIVE: The objective of this study was to determine the effect of hindlimb unloading on the outcome of Klebsiella pneumoniae infection in mice. METHODS: Hindlimb-unloaded, hindlimb-restrained, and control mice were intraperitoneally infected with one 50% lethal dose of K pneumoniae 2 days after suspension. Mortality and bacterial load in several organs were compared among the groups. RESULTS: Unloaded mice showed significantly increased mortality and reduced mean time to death compared with that seen in the control groups. Kinetics of bacterial growth with smaller infective doses revealed that control mice were able to clear bacteria from the organs after 30 hours. In contrast, unloaded mice had continued bacterial growth at the same time point. CONCLUSION: The results of this study suggest that hindlimb unloading might enhance the dissemination of K pneumoniae, leading to increased mortality. The complex physiologic changes observed during hindlimb unloading, including stress, have a key role in the pathophysiology of this infection.

  8. Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading (United States)

    Ingalls, C. P.; Warren, G. L.; Armstrong, R. B.; Hamilton, S. L. (Principal Investigator)


    The objective of this study was to determine whether altered intracellular Ca(2+) handling contributes to the specific force loss in the soleus muscle after unloading and/or subsequent reloading of mouse hindlimbs. Three groups of female ICR mice were studied: 1) unloaded mice (n = 11) that were hindlimb suspended for 14 days, 2) reloaded mice (n = 10) that were returned to their cages for 1 day after 14 days of hindlimb suspension, and 3) control mice (n = 10) that had normal cage activity. Maximum isometric tetanic force (P(o)) was determined in the soleus muscle from the left hindlimb, and resting free cytosolic Ca(2+) concentration ([Ca(2+)](i)), tetanic [Ca(2+)](i), and 4-chloro-m-cresol-induced [Ca(2+)](i) were measured in the contralateral soleus muscle by confocal laser scanning microscopy. Unloading and reloading increased resting [Ca(2+)](i) above control by 36% and 24%, respectively. Although unloading reduced P(o) and specific force by 58% and 24%, respectively, compared with control mice, there was no difference in tetanic [Ca(2+)](i). P(o), specific force, and tetanic [Ca(2+)](i) were reduced by 58%, 23%, and 23%, respectively, in the reloaded animals compared with control mice; however, tetanic [Ca(2+)](i) was not different between unloaded and reloaded mice. These data indicate that although hindlimb suspension results in disturbed intracellular Ca(2+) homeostasis, changes in tetanic [Ca(2+)](i) do not contribute to force deficits. Compared with unloading, 24 h of physiological reloading in the mouse do not result in further changes in maximal strength or tetanic [Ca(2+)](i).

  9. Actin sliding velocity on pure myosin isoforms from hindlimb unloaded mice. (United States)

    Maffei, M; Longa, E; Qaisar, R; Agoni, V; Desaphy, J-F; Camerino, D Conte; Bottinelli, R; Canepari, M


    Notwithstanding the widely accepted idea that following disuse skeletal muscles become faster, an increase in shortening velocity was previously observed mostly in fibres containing type 1 myosin, whereas a decrease was generally found in fibres containing type 2B myosin. In this study, unloaded shortening velocity of pure type 1 and 2B fibres from hindlimb unloaded mice was determined and a decrease in type 2B fibres was found. To clarify whether the decrease in shortening velocity could depend on alterations of myosin motor function, an in vitro motility assay approach was applied to study pure type 1 and pure type 2B myosin from hindlimb unloaded mice. The latter approach, assessing actin sliding velocity on isolated myosin in the absence of other myofibrillar proteins, enabled to directly investigate myosin motor function. Actin sliding velocity was significantly lower on type 2B myosin following unloading (2.70 ± 0.32 μm s(-1)) than in control conditions (4.11 ± 0.35 μm s(-1)), whereas actin sliding velocity of type 1 myosin was not different following unloading (0.89 ± 0.04 μm s(-1)) compared with control conditions (0.84 ± 0.17 μm s(-1)). Myosin light chain (MLC) isoform composition of type 2B myosin from hindlimb unloaded and control mice was not different. No oxidation of either type 1 or 2B myosin was observed. Higher phosphorylation of regulatory MLC in type 2B myosin after unloading was found. Results suggest that the observed lower shortening velocity of type 2B fibres following unloading could be related to slowing of acto-myosin kinetics in the presence of MLC phosphorylation. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  10. Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading (United States)

    Aviles, Hernan; Belay, Tesfaye; Vance, Monique; Sonnenfeld, Gerald


    The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

  11. Time course of hepatic gluconeogenesis during hindlimb suspension unloading. (United States)

    Bederman, Ilya R; Chandramouli, Visvanathan; Sandlers, Yana; Henderson, Leigh; Cabrera, Marco E


    The goal of this work was to determine the time-dependent changes in fractional hepatic gluconeogenesis (GNG) during conditions of hindlimb suspension unloading (HSU), a 'ground-based' method for inducing muscular atrophy to simulate space flight. We hypothesized that GNG would increase in HSU conditions as a result of metabolic shifts in the liver and skeletal muscle. A significant and progressive atrophy was observed in the soleus (30, 47 and 55%) and gastrocnemius muscles (0, 15 and 17%) after 3, 7 and 14 days of HSU, respectively. Fractional hepatic GNG was determined following the incorporation of deuterium from deuterated water ((2)H(2)O) into C-H bonds of newly synthesized glucose after an 8 h fast. Enrichment of plasma glucose with (2)H was measured using the classic method of Landau et al. (the 'hexamethylenetetramine (HMT) method'), based on specific (2)H labelling of glucose carbons, and the novel method of Chacko et al. ('average method'), based on the assumption of equal (2)H enrichment on all glucose carbons (except C2). After 3 days of HSU, fractional GNG was significantly elevated in the HSU group, as determined by either method (∼13%, P enrichment, we postulated that the underestimation of gluconeogenic rate was as a result of differences in the measurements of product enrichment ((2)H labelling of plasma glucose). This could be explained by the following factors: (i) loss of deuterium via exchange between acetate and glucose; (ii) interference caused by fragment m/z 169, representing multiple isobaric species; and (iii) interference from other sugars at m/z 169. In conclusion, HSU caused a time-dependent increase in hepatic gluconeogenesis, irrespective of the analytical methods used.

  12. ERK is involved in the reorganization of somatosensory cortical maps in adult rats submitted to hindlimb unloading.

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    Erwan Dupont

    Full Text Available Sensorimotor restriction by a 14-day period of hindlimb unloading (HU in the adult rat induces a reorganization of topographic maps and receptive fields. However, the underlying mechanisms are still unclear. Interest was turned towards a possible implication of intracellular MAPK signaling pathway since Extracellular-signal-Regulated Kinase 1/2 (ERK1/2 is known to play a significant role in the control of synaptic plasticity. In order to better understand the mechanisms underlying cortical plasticity in adult rats submitted to a sensorimotor restriction, we analyzed the time-course of ERK1/2 activation by immunoblot and of cortical reorganization by electrophysiological recordings, on rats submitted to hindlimb unloading over four weeks. Immunohistochemistry analysis provided evidence that ERK1/2 phosphorylation was increased in layer III neurons of the somatosensory cortex. This increase was transient, and parallel to the changes in hindpaw cortical map area (layer IV. By contrast, receptive fields were progressively enlarged from 7 to 28 days of hindlimb unloading. To determine whether ERK1/2 was involved in cortical remapping, we administered a specific ERK1/2 inhibitor (PD-98059 through osmotic mini-pump in rats hindlimb unloaded for 14 days. Results demonstrate that focal inhibition of ERK1/2 pathway prevents cortical reorganization, but had no effect on receptive fields. These results suggest that ERK1/2 plays a role in the induction of cortical plasticity during hindlimb unloading.

  13. Contribution of social isolation, restraint, and hindlimb unloading to changes in hemodynamic parameters and motion activity in rats.

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    Darya Tsvirkun

    Full Text Available The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint, and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient.

  14. Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight (United States)

    Morey-Holton, E. R.; Globus, R. K.


    A model that uses hindlimb unloading of rats was developed to study the consequences of skeletal unloading and reloading as occurs during and following space flight. Studies using the model were initiated two decades ago and further developed at National Aeronautics and Space Administration (NASA)-Ames Research Center. The model mimics some aspects of exposure to microgravity by removing weightbearing loads from the hindquarters and producing a cephalic fluid shift. Unlike space flight, the forelimbs remain loaded in the model, providing a useful internal control to distinguish between the local and systemic effects of hindlimb unloading. Rats that are hindlimb unloaded by tail traction gain weight at the same rate as pairfed controls, and glucocorticoid levels are not different from controls, suggesting that systemic stress is minimal. Unloaded bones display reductions in cancellous osteoblast number, cancellous mineral apposition rate, trabecular bone volume, cortical periosteal mineralization rate, total bone mass, calcium content, and maturation of bone mineral relative to controls. Subsequent studies reveal that these changes also occur in rats exposed to space flight. In hindlimb unloaded rats, bone formation rates and masses of unloaded bones decline relative to controls, while loaded bones do not change despite a transient reduction in serum 1,25-dihydroxyvitamin D (1,25D) concentrations. Studies using the model to evaluate potential countermeasures show that 1,25D, growth hormone, dietary calcium, alendronate, and muscle stimulation modify, but do not completely correct, the suppression of bone growth caused by unloading, whereas continuous infusion of transforming growth factor-beta2 or insulin-like growth factor-1 appears to protect against some of the bone changes caused by unloading. These results emphasize the importance of local as opposed to systemic factors in the skeletal response to unloading, and reveal the pivotal role that osteoblasts play in

  15. Bowman-Birk inhibitor concentrate prevents atrophy, weakness, and oxidative stress in soleus muscle of hindlimb-unloaded mice. (United States)

    Arbogast, Sandrine; Smith, Jacqueline; Matuszczak, Yves; Hardin, Brian J; Moylan, Jennifer S; Smith, Jeffrey D; Ware, Jeffrey; Kennedy, Ann R; Reid, Michael B


    Antigravity muscles atrophy and weaken during prolonged mechanical unloading caused by bed rest or spaceflight. Unloading also induces oxidative stress in muscle, a putative cause of weakness. We tested the hypothesis that dietary supplementation with Bowman-Birk inhibitor concentrate (BBIC), a soy protein extract, would oppose these changes. Adult mice were fed a diet supplemented with 1% BBIC during hindlimb unloading for up to 12 days. Soleus muscles of mice fed the BBIC-supplemented diet weighed less, developed less force per cross-sectional area, and developed less total force after unloading than controls. BBIC supplementation was protective, blunting decrements in soleus muscle weight and force. Cytosolic oxidant activity was assessed using 2',7'-dichlorofluorescin diacetate. Oxidant activity increased in unloaded muscle, peaking at 3 days and remaining elevated through 12 days of unloading. Increases in oxidant activity correlated directly with loss of muscle mass and were abolished by BBIC supplementation. In vitro assays established that BBIC directly buffers reactive oxygen species and also inhibits serine protease activity. We conclude that dietary supplementation with BBIC protects skeletal muscle during prolonged unloading, promoting redox homeostasis in muscle fibers and blunting atrophy-induced weakness.

  16. Allopurinol mitigates muscle contractile dysfunction caused by hindlimb unloading in mice. (United States)

    Matuszczak, Yves; Arbogast, Sandrine; Reid, Michael B


    Prolonged mechanical unloading induces skeletal muscle weakness, a major problem following extended bed rest or spaceflight. Antioxidants are reported to partially inhibit the weakness caused by limb immobilization. The current study tested allopurinol, a xanthine oxidase inhibitor with antioxidant properties, for its capacity to protect the function of unloaded antigravity muscles. Adult mice conditioned by 12 d of hindlimb suspension, with or without allopurinol 50 mg x kg(-1) x d(-1), were compared with freely ambulating controls. Animals were anesthetized and soleus muscles were isolated for ex vivo analyses. Relative to control muscles, unloading decreased soleus weight (-44%; p muscle (p muscle atrophy. The drug also blunted compliance changes in the passive muscle (p muscle caused by prolonged unloading. However, allopurinol does lessen the contractile dysfunction caused by unloading, an action that may have potential benefit for astronauts and bedridden individuals.

  17. Hindlimb unloading induces a collagen isoform shift in the soleus muscle of the rat (United States)

    Miller, T. A.; Lesniewski, L. A.; Muller-Delp, J. M.; Majors, A. K.; Scalise, D.; Delp, M. D.


    To determine whether hindlimb unloading (HU) alters the extracellular matrix of skeletal muscle, male Sprague-Dawley rats were subjected to 0 (n = 11), 1 (n = 11), 14 (n = 13), or 28 (n = 11) days of unloading. Remodeling of the soleus and plantaris muscles was examined biochemically for collagen abundance via measurement of hydroxyproline, and the percentage of cross-sectional area of collagen was determined histologically with picrosirius red staining. Total hydroxyproline content in the soleus and plantaris muscles was unaltered by HU at any time point. However, the relative proportions of type I collagen in the soleus muscle decreased relative to control (Con) with 14 and 28 days HU (Con 68 +/- 5%; 14 days HU 53 +/- 4%; 28 days HU 53 +/- 7%). Correspondingly, type III collagen increased in soleus muscle with 14 and 28 days HU (Con 32 +/- 5%; 14 days HU 47 +/- 4%; 28 days HU 48 +/- 7%). The proportion of type I muscle fibers in soleus muscle was diminished with HU (Con 96 +/- 2%; 14 days HU 86 +/- 1%; 28 days HU 83 +/- 1%), and the proportion of hybrid type I/IIB fibers increased (Con 0%; 14 days HU 8 +/- 2%; 28 days HU 14 +/- 2%). HU had no effect on the proportion of type I and III collagen or muscle fiber composition in plantaris muscle. The data demonstrate that HU induces a shift in the relative proportion of collagen isoform (type I to III) in the antigravity soleus muscle, which occurs concomitantly with a slow-to-fast myofiber transformation.

  18. Preventive effects of nucleoprotein supplementation combined with intermittent loading on capillary regression induced by hindlimb unloading in rat soleus muscle. (United States)

    Hirayama, Yusuke; Nakanishi, Ryosuke; Maeshige, Noriaki; Fujino, Hidemi


    Physical inactivity leads to muscle atrophy and capillary regression in the skeletal muscle. Intermittent loading during hindlimb unloading attenuates the muscle atrophy, meanwhile the capillary regression in the skeletal muscle is not suppressed. Nucleoprotein has antioxidant capacity and may prevent capillary regression. Therefore, we assessed the combined effects of intermittent loading with nucleoprotein supplementation on capillary regression induced by hindlimb unloading. Five groups of rats were assigned: control (CON), 7 days hindlimb unloading (HU), HU plus nucleoprotein supplementation (HU + NP), intermittent loading during HU (HU + IL), and intermittent loading combined with nucleoprotein supplementation during HU (HU + IL + NP). Seven days HU resulted in decrease in capillary number-to-fiber number (C/F) ratio accompanied with disuse-associated changes in fetal liver kinase-1 (Flk-1), a proangiogenesis factor, and thrombospondin-1 (TSP-1), an antiangiogenesis factor, in the soleus muscle. In addition, citrate synthase (CS) activity was decreased and protein level of superoxide dismutase (SOD)-2 was increased. Neither nucleoprotein supplementation nor intermittent loading prevented the decrease in the C/F ratio, whereas nucleoprotein supplementation combined with intermittent loading prevented the regression of capillary during unloading. Moreover, the levels of Flk-1, TSP-1, and SOD-2 protein and the CS activity were maintained up to control levels. These results suggested that nucleoprotein supplementation combined with intermittent loading was effective to prevent capillary regression induced by muscle atrophy. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  19. Eccentric exercise prior to hindlimb unloading attenuated reloading muscle damage in rats. (United States)

    Prisby, Rhonda D; Nelson, Arnold G; Latsch, Elizabeth


    Antigravity muscles that are reloaded subsequent to hindlimb unloading (HU) are prone to injury. Similarities exist between muscle damage elicited from HU and subsequent reloading and damage induced by eccentric exercise (EE). Conditioning bouts of EE reduce muscle damage following a repeat bout of EE. Since damage to reloaded skeletal muscle is comparable to damage observed after EE, the mechanisms of damage are presumably similar. Therefore, EE prior to HU may attenuate reloading muscle damage. This study evaluated the effects of prior EE on rat soleus muscles (SOL) subsequent to 7 d of HU and 16-19 h of reloading. Sprague Dawley rats were randomly assigned to the following groups: eccentric exercise + hindlimb unloading + reloading (EEHUR; n = 9); hindlimb unloading + reloading (HUR; n = 10); eccentric exercise (EE; n = 12), or control (CON; n = 12). The exercise protocol was performed 5 d x wk(-1) for 2 wks followed by HU and reloading. Fiber areas were lower in both suspended groups vs. the EE and CON groups. There was no difference in percent interstitial area among groups. However, percent myofibrillar damage was higher in the HUR group vs. all other groups. Further, glucose-6-phospate dehydrogenase activity, an indicator of muscle damage, was higher in the HUR group compared with the EE and CON groups. These results provide some evidence that prior EE reduced muscle damage subsequent to HU and reloading. Therefore, EE may prove effective in minimizing recovery time in individuals suffering from muscle damage following periods of bed rest and spaceflight.

  20. A hypomagnetic field aggravates bone loss induced by hindlimb unloading in rat femurs.

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    Bin Jia

    Full Text Available A hypomagnetic field is an extremely weak magnetic field--it is considerably weaker than the geomagnetic field. In deep-space exploration missions, such as those involving extended stays on the moon and interplanetary travel, astronauts will experience abnormal space environments involving hypomagnetic fields and microgravity. It is known that microgravity in space causes bone loss, which results in decreased bone mineral density. However, it is unclear whether hypomagnetic fields affect the skeletal system. In the present study, we aimed to investigate the complex effects of a hypomagnetic field and microgravity on bone loss. To study the effects of hypomagnetic fields on the femoral characteristics of rats in simulated weightlessness, we established a rat model of hindlimb unloading that was exposed to a hypomagnetic field. We used a geomagnetic field-shielding chamber to generate a hypomagnetic field of <300 nT. The results show that hypomagnetic fields can exacerbate bone mineral density loss and alter femoral biomechanical characteristics in hindlimb-unloaded rats. The underlying mechanism might involve changes in biological rhythms and the concentrations of trace elements due to the hypomagnetic field, which would result in the generation of oxidative stress responses in the rat. Excessive levels of reactive oxygen species would stimulate osteoblasts to secrete receptor activator of nuclear factor-κB ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption.

  1. Antioxidant treatment of hindlimb-unloaded mouse counteracts fiber type transition but not atrophy of disused muscles. (United States)

    Desaphy, Jean-François; Pierno, Sabata; Liantonio, Antonella; Giannuzzi, Viviana; Digennaro, Claudio; Dinardo, Maria Maddalena; Camerino, Giulia M; Ricciuti, Patrizia; Brocca, Lorenza; Pellegrino, Maria Antonietta; Bottinelli, Roberto; Camerino, Diana Conte


    Oxidative stress was proposed as a trigger of muscle impairment in various muscle diseases. The hindlimb-unloaded (HU) rodent is a model of disuse inducing atrophy and slow-to-fast transition of postural muscles. Here, mice unloaded for 14 days were chronically treated with the selective antioxidant trolox. After HU, atrophy was more pronounced in the slow-twitch soleus muscle (Sol) than in the fast-twitch gastrocnemius and tibialis anterior muscles, and was absent in extensor digitorum longus muscle. In accord with the phenotype transition, HU Sol showed a reduced expression of myosin heavy chain type 2A (MHC-2A) and increase in MHC-2X and MHC-2B isoforms. In parallel, HU Sol displayed an increased sarcolemma chloride conductance related to an increased expression of ClC-1 channels, changes in excitability parameters, a positive shift of the mechanical threshold, and a decrease of the resting cytosolic calcium concentration. Moreover, the level of lipoperoxidation increased proportionally to the degree of atrophy of each muscle type. As expected, trolox treatment fully prevented oxidative stress in HU mice. Atrophy was not prevented but the drug significantly attenuated Sol phenotypic transition and excitability changes. Trolox treatment had no effect on control mice. These results suggest possible benefits of antioxidants in protecting muscle against disuse. (c) 2010 Elsevier Ltd. All rights reserved.

  2. Potential benefits of taurine in the prevention of skeletal muscle impairment induced by disuse in the hindlimb-unloaded rat. (United States)

    Pierno, Sabata; Liantonio, Antonella; Camerino, Giulia M; De Bellis, Michela; Cannone, Maria; Gramegna, Gianluca; Scaramuzzi, Antonia; Simonetti, Simonetta; Nicchia, Grazia Paola; Basco, Davide; Svelto, Maria; Desaphy, Jean-François; Camerino, Diana Conte


    Hindlimb unloading (HU) in rats induces severe atrophy and a slow-to-fast phenotype transition in postural slow-twitch muscles, as occurs in human disuse conditions, such as spaceflight or bed rest. In rats, a reduction of soleus muscle weight and a decrease of cross-sectional area (CSA) were observed as signs of atrophy. An increased expression of the fast-isoform of myosin heavy chain (MHC) showed the phenotype transition. In parallel the resting cytosolic calcium concentration (restCa) was decreased and the resting chloride conductance (gCl), which regulates muscle excitability, was increased toward the values of the fast-twitch muscles. Here, we investigated the possible role of taurine, which is known to modulate calcium homeostasis and gCl, in the restoration of muscle impairment due to 14-days-HU. We found elevated taurine content and higher expression of the taurine transporter TauT in the soleus muscle as compared to the fast-twitch extensor digitorum longus (EDL) muscle of control rats. Taurine level was reduced in the HU soleus muscle, although, TauT expression was not modified. Taurine oral supplementation (5 g/kg) fully prevented this loss, and preserved resting gCl and restCa together with the slow MHC phenotype. Taurine supplementation did not prevent the HU-induced drop of muscle weight or fiber CSA, but it restored the expression of MURF-1, an atrophy-related gene, suggesting a possible early protective effect of taurine. In conclusion, taurine prevented the HU-induced phenotypic transition of soleus muscle and might attenuate the atrophic process. These findings argue for the beneficial use of taurine in the treatment of disuse-induced muscle dysfunction.

  3. Gene expression patterns in bone after 4 days of hind-limb unloading in two inbred strains of mice. (United States)

    Zhong, Nan; Garman, Russell A; Squire, Maria E; Donahue, Leah Rae; Rubin, Clinton T; Hadjiargyrou, Michael; Judex, Stefan


    An improved understanding of the interdependence of transcriptional and genomic control of bone loss is critical for the design of effective and safe countermeasures for osteoporosis in space and on Earth. In an effort to test whether molecular pathways modulating the loss of functional weight bearing are dependent on genetic makeup, we quantified the differential expression of genes critical to the early stages of bone remodeling in two different strains of mice. Adult (4-mo-old) female BALB/cByJ (BALB) and C3H/HeJ (C3H) mice, strains with different sensitivities to unloading, were subjected to hind-limb unloading (HLU) or normal cage activities. RNA was extracted from the tibia following 4 d of HLU and expression levels were determined. In the BALB mice, HLU significantly altered transcriptional levels of osterix (-36%), alkaline phosphatase (-36%), osteonectin (-44%), collagen type 1 (-55%), MMP2 (-36%), osteocalcin (-68%), and osteopontin (+28%). This expression pattern was highly correlated (R2 = 0.75) with altered expression levels in the C3H mice, but the magnitude of altered mRNA levels was less than half of those in the BALB mice. These strain-specific changes in gene expression were consistent with the differential changes in bone formation, as determined in a second group of BALB and C3H mice. These data indicate that genetics may influence the absolute changes in gene expression of genes during spaceflight, but that the molecular pathways targeted by countermeasures of bone loss may not need to be specific to an individual's genetic makeup.

  4. Recovery of the soleus muscle after short- and long-term disuse induced by hindlimb unloading: effects on the electrical properties and myosin heavy chain profile. (United States)

    Desaphy, Jean-François; Pierno, Sabata; Liantonio, Antonella; De Luca, Annamaria; Didonna, M Paola; Frigeri, Antonio; Nicchia, G Paola; Svelto, Maria; Camerino, Claudia; Zallone, Alberta; Camerino, Diana Conte


    The hindlimb unloading (HU) rat is a model of muscle disuse characterized by atrophy and slow-to-fast phenotype transition of the postural muscles, such as the soleus. We previously found that the resting sarcolemmal chloride conductance (gCl) that is typically lower in slow-twitch myofibers than in fast ones increased in soleus fibers following 1 to 3 weeks of HU in accord with the slow-to-fast transition of myosin heavy chain (MHC) isoforms. Nevertheless, the gCl already raised after a 3-day HU, whereas no change in MHC expression was detected. The present work evaluates the ability of soleus muscle to recover on return to normal load after a short (3 days) or long (2 weeks) disuse period. The changes observed after a 2-week HU were slowly reversible, since 3-4 weeks of reloading were needed to completely recover gCl, fiber diameter, MHC expression pattern, as well as the mechanical threshold Rheobase, an index of calcium homeostasis. After 3-day HU, the gCl increased homogeneously in most of the soleus muscle fibers and gCl recovery was rapidly completed after 4-day reloading. These results suggest different induction mechanisms for gCl augmentation after the short and long HU periods, as well as a possible role for gCl in the slow muscle adaptation to disuse.

  5. Local vibration enhanced the efficacy of passive exercise on mitigating bone loss in hindlimb unloading rats (United States)

    Huang, Yunfei; Luan, Huiqin; Sun, Lianwen; Bi, Jingfang; Wang, Ying; Fan, Yubo


    Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the

  6. Tetramethylpyrazine ameliorated disuse-induced gastrocnemius muscle atrophy in hindlimb unloading rats through suppression of Ca2+/ROS-mediated apoptosis. (United States)

    Hu, Nai-Fei; Chang, Hui; Du, Bei; Zhang, Quan-Wang; Arfat, Yasir; Dang, Kai; Gao, Yun-Fang


    The purpose of this study was to examine the possible mechanism underlying the protective effect of tetramethylpyrazine (TMP) against disuse-induced muscle atrophy. Sprague-Dawley rats were randomly assigned to receive 14 days of hindlimb unloading (HLU, a model of disuse atrophy) or cage controls. The rats were given TMP (60 mg/kg body mass) or vehicle (water) by gavage. Compared with vehicle treatment, TMP significantly attenuated the loss of gastrocnemius muscle mass (-33.56%, P < 0.01), the decrease of cross-sectional area of slow fiber (-10.99%, P < 0.05) and fast fiber (-15.78%, P < 0.01) during HLU. Although TMP failed to further improve recovery of muscle function or fatigability compared with vehicle treatment, it can suppress the higher level of lactate (-22.71%, P < 0.01) induced by HLU. Besides, TMP could effectually reduce the increased protein expression of muscle RING-finger protein 1 induced by HLU (-14.52%, P < 0.01). Furthermore, TMP can ameliorate the calcium overload (-54.39%, P < 0.05), the increase of malondialdehyde content (-19.82%, P < 0.05), the decrease of superoxide dismutase activity (21.34%, P < 0.05), and myonuclear apoptosis (-78.22%, P < 0.01) induced by HLU. Moreover, TMP significantly reduced HLU-induced increase of Bax to B-cell lymphoma 2 (-36.36%, P < 0.01) and cytochrome c release (-36.16%, P < 0.05). In conclusion, TMP attenuated HLU-induced gastrocnemius muscle atrophy through suppression of Ca2+/reactive oxygen species increase and consequent proteolysis and apoptosis. Therefore, TMP might exhibit therapeutic effect against oxidative stress, cytosolic calcium overload, and mitochondrial damage in disuse-induced muscle atrophy.

  7. Three weeks of murine hindlimb unloading induces shifts from B to T and from th to tc splenic lymphocytes in absence of stress and differentially reduces cell-specific mitogenic responses.

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    Fanny Gaignier

    Full Text Available Extended space missions are known to induce stress and immune dysregulation. Hindlimb unloading is a ground-based model used to reproduce most spaceflight conditions. The aim of this study was to better characterize the consequences of prolonged exposure to hindlimb unloading on murine splenic lymphocyte sub-populations. To ensure that the observed changes were not due to tail restraint but to the antiorthostatic position, three groups of mice were used: control (C, orthostatic restrained (R and hindlimb unloaded (HU. After 21 days of exposure, no difference in serum corticosterone levels nor in thymus and spleen weights were observed between HU mice and their counterparts, revealing a low state of stress. Interestingly, flow cytometric analyses showed that B cells were drastically reduced in HU mouse spleens by 59% and, while the T cells number did not change, the Th/Tc ratio was decreased. Finally, the use of a fluorescent dye monitoring lymphoproliferation demonstrated that lymphocyte response to mitogen was reduced in Th and Tc populations and to a greater extent in B cells. Thus, we showed for the first time that, even if restraint has its own effects on the animals and their splenic lymphocytes, the prolonged antiorthostatic position leads, despite the absence of stress, to an inversion of the B/T ratio in the spleen. Furthermore, the lymphoproliferative response was impaired with a strong impact on B cells. Altogether, these results suggest that B cells are more affected by hindlimb unloading than T cells which may explain the high susceptibility to pathogens, such as gram-negative bacteria, described in animal models and astronauts.

  8. Anodisation Increases Integration of Unloaded Titanium Implants in Sheep Mandible

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    Warwick J. Duncan


    Full Text Available Spark discharge anodic oxidation forms porous TiO2 films on titanium implant surfaces. This increases surface roughness and concentration of calcium and phosphate ions and may enhance early osseointegration. To test this, forty 3.75 mm × 13 mm titanium implants (Megagen, Korea were placed into healed mandibular postextraction ridges of 10 sheep. There were 10 implants per group: RBM surface (control, RBM + anodised, RBM + anodised + fluoride, and titanium alloy + anodised surface. Resonant frequency analysis (RFA was measured in implant stability quotient (ISQ at surgery and at sacrifice after 1-month unloaded healing. Mean bone-implant contact (% BIC was measured in undemineralised ground sections for the best three consecutive threads. One of 40 implants showed evidence of failure. RFA differed between groups at surgery but not after 1 month. RFA values increased nonsignificantly for all implants after 1 month, except for controls. There was a marked difference in BIC after 1-month healing, with higher values for alloy implants, followed by anodised + fluoride and anodised implants. Anodisation increased early osseointegration of rough-surfaced implants by 50–80%. RFA testing lacked sufficient resolution to detect this improvement. Whether this gain in early bone-implant contact is clinically significant is the subject of future experiments.

  9. Muscle sarcomere lesions and thrombosis after spaceflight and suspension unloading

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    Riley, D.A.; Ellis, S.; Giometti, C.S.; Hoh, J.F.Y.; Ilyina-Kakueva, E.I.; Oganov, V.S.; Slocum, G.R.; Bain, J.L.W.; Sedlak, F.R. (Argonne National Lab., IL (United States))


    Extended exposure of humans to spaceflight produces a progressive loss of skeletal muscle strength. This process must be understood to design effective countermeasures. The present investigation examined hindlimb muscles from flight rats killed as close to landing as possible. Spaceflight and tail suspension-hindlimb unloading (unloaded) produced significant decreases in fiber cross-sectional areas of the adductor longus (AL), a slow-twitch antigravity muscle. However, the mean wet weight of the flight AL muscles was near normal, whereas that of the suspension unloaded AL muscles was significantly reduced. Interstitial edema within the flight AL, but not in the unloaded AL, appeared to account for this apparent disagreement.In both conditions, the slow-twitch oxidative fibers atrophied more than the fast-twitch oxidative-glycolytic fibers. Microcirculation was also compromised by spaceflight, such that there was increased formation of thrombi in the postcapillary venules and capillaries.

  10. Paracrine effects of IGF-1 overexpression on the functional decline due to skeletal muscle disuse: molecular and functional evaluation in hindlimb unloaded MLC/mIgf-1 transgenic mice. (United States)

    Pierno, Sabata; Camerino, Giulia M; Cannone, Maria; Liantonio, Antonella; De Bellis, Michela; Digennaro, Claudio; Gramegna, Gianluca; De Luca, Annamaria; Germinario, Elena; Danieli-Betto, Daniela; Betto, Romeo; Dobrowolny, Gabriella; Rizzuto, Emanuele; Musarò, Antonio; Desaphy, Jean-François; Camerino, Diana Conte


    Slow-twitch muscles, devoted to postural maintenance, experience atrophy and weakness during muscle disuse due to bed-rest, aging or spaceflight. These conditions impair motion activities and can have survival implications. Human and animal studies demonstrate the anabolic role of IGF-1 on skeletal muscle suggesting its interest as a muscle disuse countermeasure. Thus, we tested the role of IGF-1 overexpression on skeletal muscle alteration due to hindlimb unloading (HU) by using MLC/mIgf-1 transgenic mice expressing IGF-1 under the transcriptional control of MLC promoter, selectively activated in skeletal muscle. HU produced atrophy in soleus muscle, in terms of muscle weight and fiber cross-sectional area (CSA) reduction, and up-regulation of atrophy gene MuRF1. In parallel, the disuse-induced slow-to-fast fiber transition was confirmed by an increase of the fast-type of the Myosin Heavy Chain (MHC), a decrease of PGC-1α expression and an increase of histone deacetylase-5 (HDAC5). Consistently, functional parameters such as the resting chloride conductance (gCl) together with ClC-1 chloride channel expression were increased and the contractile parameters were modified in soleus muscle of HU mice. Surprisingly, IGF-1 overexpression in HU mice was unable to counteract the loss of muscle weight and the decrease of fiber CSA. However, the expression of MuRF1 was recovered, suggesting early effects on muscle atrophy. Although the expression of PGC-1α and MHC were not improved in IGF-1-HU mice, the expression of HDAC5 was recovered. Importantly, the HU-induced increase of gCl was fully contrasted in IGF-1 transgenic mice, as well as the changes in contractile parameters. These results indicate that, even if local expression does not seem to attenuate HU-induced atrophy and slow-to-fast phenotype transition, it exerts early molecular effects on gene expression which can counteract the HU-induced modification of electrical and contractile properties. MuRF1 and HDAC5

  11. The regulation of iron metabolism by hepcidin contributes to unloading-induced bone loss. (United States)

    Xu, Zi; Sun, Weijia; Li, Yuheng; Ling, Shukuan; Zhao, Chenyang; Zhong, Guohui; Zhao, Dingsheng; Song, Jinping; Song, Hailin; Li, Jinqiao; You, Linhao; Nie, Guangjun; Chang, Yanzhong; Li, Yingxian


    Iron overload inhibits osteoblast function and promotes osteoclastogenesis. Hepcidin plays an important role in this process. The changes in iron content and the regulation of hepcidin under unloading-induced bone loss remain unknown. A hindlimb suspension model was adopted to simulate unloading-induced bone loss in mice. The results showed that iron deposition in both liver and bone was markedly increased in hindlimb unloaded mice, and was accompanied by the upregulation of osteoclast activity and downregulation of osteoblast activity. The iron chelator deferoxamine mesylate (DFO) reduced the iron content in bone and alleviated unloading-induced bone loss. The increased iron content in bone was mainly a result of the upregulation of transferrin receptor 1 (TfR1) and divalent metal transporter 1 with iron response element (DMT1+IRE), rather than changes in the iron transporter ferroportin 1 (FPN1). The hepcidin level in the liver was significantly higher, while the FPN1 level in the duodenum was substantially reduced. However, there were no changes in the FPN1 level in bone tissue. During hindlimb unloading, downregulation of hepcidin by siRNA increased iron uptake in bone and liver, which aggravated unloading-induced bone loss. In summary, these data show that unloading-induced bone loss was orchestrated by iron overload and coupled with the regulation of hepcidin by the liver. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments

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    Martinez Daniel A


    Full Text Available Abstract Background Insulin-like growth factor-I (IGF-I plays a crucial role in wound healing and tissue repair. We tested the hypotheses that systemic administration of IGF-I, or growth hormone (GH, or both (GH+IGF-I would improve healing in collagenous connective tissue, such as ligament. These hypotheses were examined in rats that were allowed unrestricted activity after injury and in animals that were subjected to hindlimb disuse. Male rats were assigned to three groups: ambulatory sham-control, ambulatory-healing, and hindlimb unloaded-healing. Ambulatory and hindlimb unloaded animals underwent surgical disruption of their knee medial collateral ligaments (MCLs, while sham surgeries were performed on control animals. Healing animals subcutaneously received systemic doses of either saline, GH, IGF-I, or GH+IGF-I. After 3 weeks, mechanical properties, cell and matrix morphology, and biochemical composition were examined in control and healing ligaments. Results Tissues from ambulatory animals receiving only saline had significantly greater strength than tissue from saline receiving hindlimb unloaded animals. Addition of IGF-I significantly improved maximum force and ultimate stress in tissues from both ambulatory and hindlimb unloaded animals with significant increases in matrix organization and type-I collagen expression. Addition of GH alone did not have a significant effect on either group, while addition of GH+IGF-I significantly improved force, stress, and modulus values in MCLs from hindlimb unloaded animals. Force, stress, and modulus values in tissues from hindlimb unloaded animals receiving IGF-I or GH+IGF-I exceeded (or were equivalent to values in tissues from ambulatory animals receiving only saline with greatly improved structural organization and significantly increased type-I collagen expression. Furthermore, levels of IGF-receptor were significantly increased in tissues from hindlimb unloaded animals treated with IGF

  13. [Parameters of fibers cell respiration and desmin content in rat soleus muscle at early stages of gravitational unloading]. (United States)

    Mirzoev, T M; Biriukov, N S; Veselova, O M; Larina, I M; Shenkman, B S; Ogneva, I V


    The aim of the work was to study the parameters of fibers cell respiration and desmin content in Wistar rat soleus muscle after 1, 3, 7 and 14 days of gravitational unloading. Gravitational unloading was simulated by antiorthostatic hindlimb suspension. The parameters of cell respiration were determined using the polarography, and desmin content was assessed by means of Western blotting. The results showed that the intensity of cell respiration is reduced after three days of gravitational unloading, reaches a minimum level after seven days and slightly increases by the fourteenth day of hindlimb unloading, as well as the content of desmin, which, however, to the fourteenth day returns to the control level. Taking into account that mitochondrial function depends on the state of cytoskeleton the data allow us to assume that early reduction of the intensity of cell respiration under unloading could be caused by degradation of the protein desmin that determines intracellular localization of mitochondria.

  14. Key Markers of mTORC1-Dependent and mTORC1-Independent Signaling Pathways Regulating Protein Synthesis in Rat Soleus Muscle During Early Stages of Hindlimb Unloading

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    Timur Mirzoev


    Full Text Available Background/Aims: The purpose of the study was to assess the amount of rRNA and phosphorylation status of the key markers of mTORC1-dependent (70s6k, 4E-BP1 and mTORC1-independent (GSK-3β, AMPK signaling pathways controlling protein synthesis in rat soleus during early stages of mechanical unloading (hindlimb suspension (HS for 1-, 3- and 7 days. Methods: The content of the key signaling molecules of various anabolic signaling pathways was determined by Western-blotting. The amount of 28S rRNA was evaluated by RT-PCR. The rate of protein synthesis was assessed using in-vivo SUnSET technique. Results: HS for 3 and 7 days induced a significant (pConclusion: Taken together, the results of our study suggest that a decline in the global rate of protein synthesis in rat soleus during early stages of simulated microgravity is associated with impaired ribosome biogenesis as well as reduced activity of mTORC1-independent signaling pathways.

  15. Haemodynamic unloading increases the survival and affects the differentiation of cardiac stem cells after implantation into an infarcted heart. (United States)

    Kurazumi, Hiroshi; Li, Tao-Sheng; Takemoto, Yoshihiro; Suzuki, Ryo; Mikamo, Akihito; Guo, Chang-Ying; Murata, Tomoaki; Hamano, Kimikazu


    It has been anticipated that stem cell therapy is capable of repairing an injured heart but is currently limited by its marginal efficacy. We believe that mechanical stress due to haemodynamic loading may negate the therapeutic potency of stem cells and therefore investigated how haemodynamic unloading affects the survival and differentiation of stem cells after implantation into an infarcted heart. A left ventricular (LV) haemodynamic unloading model was implemented by heterotopic transplantation of an infarcted donor heart into another healthy mouse. An in situ infarcted heart with general haemodynamic loading was used as control. A total of 5 million cardiac stem cells expanded from green fluorescence protein (GFP)-transgenic mouse were intramyocardially implanted into the infarcted LVs of haemodynamically unloaded donor heart or general haemodynamic loaded heart. The survival and differentiation of the implanted cardiac stem cells were evaluated by histological analyses at 3 and 21 days after cell implantation (n = 5-6 in each time points per group). Compared with the general haemodynamic loading condition, haemodynamic unloading of the infarcted hearts significantly improved the survival, increased the proliferation and inhibited the apoptosis of cardiac stem cells at 21 days after cell implantation (P cells was much higher in the unloaded hearts than in the loaded hearts at 21 days after cell implantation, although the difference was not statistically significant (5.67 ± 5.10 vs 0.75 ± 0.50, P = 0.051). Among the surviving GFP(+) donor cells 21 days after implantation, the expressions of platelet endothelial cell adhesion molecule-1, smooth muscle actin and sarcomeric alpha actin were ~7, 38 and 27% in the loaded heart and ~19, 14 and 55% in the unloaded heart, respectively. Haemodynamic unloading favours the survival/engraftment of donor stem cells and affects their differentiation after implantation into an infarcted heart. Although further studies in a

  16. Effect of hindlimb suspension and clenbuterol treatment on polyamine levels in skeletal muscle (United States)

    Abukhalaf, Imad K.; von Deutsch, Daniel A.; Wineski, Lawrence E.; Silvestrov, Natalia A.; Abera, Saare A.; Sahlu, Sinafikish W.; Potter, David E.; Thierry-Palmer, M. (Principal Investigator)


    Polyamines are unbiquitous, naturally occurring small aliphatic, polycationic, endogenous compounds. They are involved in many cellular processes and may serve as secondary or tertiary messengers to hormonal regulation. The relationship of polyamines and skeletal muscle mass of adductor longus, extensor digitorum longus, and gastrocnemius under unloading (hindlimb suspension) conditions was investigated. Unloading significantly affected skeletal muscle polyamine levels in a fiber-type-specific fashion. Under loading conditions, clenbuterol treatment increased all polyamine levels, whereas under unloading conditions, only the spermidine levels were consistently increased. Unloading attenuated the anabolic effects of clenbuterol in predominately slow-twitch muscles (adductor longus), but had little impact on clenbuterol's action as a countermeasure in fast- twitch muscles such as the extensor digitorum longus. Spermidine appeared to be the primary polyamine involved in skeletal muscle atrophy/hypertrophy. Copyright 2002 S. Karger AG, Basel.

  17. Hindlimb heating increases vascular access of large molecules to murine tibial growth plates measured by in vivo multiphoton imaging. (United States)

    Serrat, Maria A; Efaw, Morgan L; Williams, Rebecca M


    Advances in understanding the molecular regulation of longitudinal growth have led to development of novel drug therapies for growth plate disorders. Despite progress, a major unmet challenge is delivering therapeutic agents to avascular-cartilage plates. Dense extracellular matrix and lack of penetrating blood vessels create a semipermeable "barrier," which hinders molecular transport at the vascular-cartilage interface. To overcome this obstacle, we used a hindlimb heating model to manipulate bone circulation in 5-wk-old female mice (n = 22). Temperatures represented a physiological range of normal human knee joints. We used in vivo multiphoton microscopy to quantify temperature-enhanced delivery of large molecules into tibial growth plates. We tested the hypothesis that increasing hindlimb temperature from 22°C to 34°C increases vascular access of large systemic molecules, modeled using 10, 40, and 70 kDa dextrans that approximate sizes of physiological regulators. Vascular access was quantified by vessel diameter, velocity, and dextran leakage from subperichondrial plexus vessels and accumulation in growth plate cartilage. Growth plate entry of 10 kDa dextrans increased >150% at 34°C. Entry of 40 and 70 kDa dextrans increased vascular carrying capacity and bioavailability of large molecules around growth plates, suggesting that temperature could be a noninvasive strategy for modulating delivery of therapeutics to impaired growth plates of children.

  18. Robot-assisted hindlimb extension increases the probability of swing initiation during treadmill walking by spinal cord contused rats. (United States)

    Nessler, Jeff A; Minakata, Koyiro; Sharp, Kelli; Reinkensmeyer, David J


    Training and evaluation of locomotion in animals with spinal cord injury will likely be improved with the development of techniques that increase stepping activity. We hypothesized that robot-assisted extension of the hindlimbs of spinal cord injured rats during stance would increase the probability that the swing phase of gait would be initiated. Thirty-three adult, Sprague-Dawley rats received a contusion injury to the mid-thoracic spinal cord. The animals' hindlimbs were pulled into extension using small robotic arms to pull at the ankle, as the rat stepped on either a reciprocating, robotic paw platform or a conventional treadmill belt. The animals demonstrated an increase in the probability of swing initiation with spontaneous recovery during the first 4 weeks following injury (p probability of swing initiation was found to be greater with the use of robot-assisted extension versus no extension force at the ankle (75+/-16.9% versus 38.9+/-16.6%, p robot-assisted extension, thereby providing possible benefits to evaluation and training of gait following SCI.

  19. Passive stretch reduces calpain activity through nitric oxide pathway in unloaded soleus muscles. (United States)

    Xu, Peng-Tao; Li, Quan; Sheng, Juan-Juan; Chang, Hui; Song, Zhen; Yu, Zhi-Bin


    Unloading in spaceflight or long-term bed rest induces to pronounced atrophy of anti-gravity skeletal muscles. Passive stretch partially resists unloading-induced atrophy of skeletal muscle, but the mechanism remains elusive. The aims of this study were to investigate the hypotheses that stretch tension might increase protein level of neuronal nitric oxide synthase (nNOS) in unloaded skeletal muscle, and then nNOS-derived NO alleviated atrophy of skeletal muscle by inhibiting calpain activity. The tail-suspended rats were used to unload rat hindlimbs for 2 weeks, at the same time, left soleus muscle was stretched by applying a plaster cast to fix the ankle at 35° dorsiflexion. Stretch partially resisted atrophy and inhibited the decreased protein level and activity of nNOS in unloaded soleus muscles. Unloading increased frequency of calcium sparks and elevated intracellular resting and caffeine-induced Ca(2+) concentration ([Ca(2+)]i) in unloaded soleus muscle fibers. Stretch reduced frequency of calcium sparks and restored intracellular resting and caffeine-induced Ca(2+) concentration to control levels in unloaded soleus muscle fibers. The increased protein level and activity of calpain as well as the higher degradation of desmin induced by unloading were inhibited by stretch in soleus muscles. In conclusion, these results suggest that stretch can preserve the stability of sarcoplasmic reticulum Ca(2+) release channels which prevents the elevated [Ca(2+)]i by means of keeping nNOS activity, and then the enhanced protein level and activity of calpain return to control levels in unloaded soleus muscles. Therefore, stretch can resist in part atrophy of unloaded soleus muscles.

  20. Regulation of contractile protein gene expression in unloaded mouse skeletal muscle (United States)

    Criswell, D. S.; Carson, J. A.; Booth, F. W.


    Hindlimb unloading was performed on mice in an effort to study the regulation of contractile protein genes. In particular, the regulation of myosin heavy chain IIb was examined. During unloading, muscle fibers undergo a type conversion. Preliminary data from this study does not support the hypothesis that the fiber type conversion is due to an increase in promoter activity of fast isoform genes, such as myosin heavy chain IIb. The consequences of this finding are examined, with particular focus on other factors controlling gene regulation.

  1. Metabolic adaptation of skeletal muscles to gravitational unloading (United States)

    Ohira, Y.; Yasui, W.; Kariya, F.; Wakatsuki, T.; Nakamura, K.; Asakura, T.; Edgerton, V. R.

    Responses of high-energy phosphates and metabolic properties to hindlimb suspension were studied in adult rats. The relative content of phosphocreatine (PCr) in the calf muscles was significantly higher in rats suspended for 10 days than in age-matched cage controls. The Pi/PCr ratio, where Pi is inorganic phosphate, in suspended muscles was less than controls. The absolute weights of soleus and medial gastrocnemius (MG) were approximately 40% less than controls. Although the % fiber distribution in MG was unchanged, the % slow fibers decreased and the % fibers which were classified as both slow and fast was increased in soleus. The activities (per unit weight or protein) of succinate dehydrogenase and lactate dehydrogenase in soleus were unchanged but those of cytochrome oxidase, β-hydroxyacyl CoA dehydrogenase, and citrate synthase were decreased following unloading. None of these enzyme activities in MG changed. However, the total levels of all enzymes in whole muscles decreased by suspension. It is suggested that shift of slow muscle toward fast type by unloading is associated with a decrease in mitochondrial biogenesis. Further, gravitational unloading affected the levels of muscle proteins differently even in the same mitochondrial enzymes. Unloading-related atrophy is prominent in red muscle or slow-twitch fiber 1, 2. Such atrophy is accompanied by a shift of contractile properties toward fast-twitch type 2-9. Further, inhibition of mitochondrial metabolism in these muscles is also reported by some studies 10-14 suggesting a lowered mitochondrial biogenesis, although results from some studies do not necessarily agree 1, 7, 15. However, the precise mechanism responsible for such alterations of muscle properties in response to gravitational unloading is unclear. On the contrary, mitochondrial biogenesis, suggested by mitochondrial enzyme activities and/or mass, is stimulated in muscles with depleted high-energy phosphates by cold exposure 16 and/or by feeding

  2. Deterioration of bone quality in the tibia and fibula in growing mice during skeletal unloading: gender-related differences. (United States)

    Ko, Chang-Yong; Seo, Dong Hyun; Kim, Han Sung


    Skeletal unloading causes bone loss in both men and women; however, only a few studies have been performed on the effects of gender differences on bone quality during skeletal unloading. Moreover, although the fibula also plays an important role in load bearing and ankle stability, the effects of unloading on the fibula have been rarely investigated. The present study aimed to investigate the effects of skeletal unloading on bone quality of the tibia and fibula in growing animals and to determine whether differences existed between genders. Six-week-old female and male mice were randomly allocated into two groups. The right hindlimb of each mouse in the skeletal unloading group was subjected to sciatic neurectomy. After two weeks of skeletal unloading, the structural characteristics of the tibia and fibula in both genders were worsened. In addition, the bone mineralization density distribution (MDD) of the tibia and fibula in both genders were altered. However, the magnitude of deterioration and alteration of the MDD in the bones of females were larger than in those of males. These results demonstrate that skeletal unloading diminishes bone quality in the tibia and fibula, leading to an increase in bone fracture risks, particularly in females.

  3. Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation (United States)

    Bikle, D. D.; Harris, J.; Halloran, B. P.; Morey-Holton, E.


    Spaceflight leads to osteopenia, in part by inhibiting bone formation. Using an animal model (hindlimb elevation) that simulates the weightlessness of spaceflight, we and others showed a reversible inhibition of bone formation and bone mineralization. In this study, we have measured the mRNA levels of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), alkaline phosphatase, and osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space Administration Shuttle Flight STS-54 and compared the results with those obtained from their ground-based controls and from the bones of hindlimb-elevated animals. Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF-I, IGF-IR, and alkaline phosphatase but decrease the mRNA levels for osteocalcin. The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent with a shift toward decreased maturation, whereas the rise in IGF-I and IGF-IR mRNA levels may indicate a compensatory response to the fall in bone formation. We conclude that skeletal unloading during spaceflight or hindlimb elevation resets the pattern of gene expression in the osteoblast, giving it a less mature profile.

  4. Impact of skeletal unloading on bone formation: Role of systemic and local factors (United States)

    Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

    We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

  5. Chronic skeletal unloading of the rat femur: mechanisms and functional consequences of vascular remodeling. (United States)

    Stabley, John N; Prisby, Rhonda D; Behnke, Bradley J; Delp, Michael D


    Chronic skeletal unloading diminishes hindlimb bone blood flow. The purpose of the present investigation was to determine 1) whether 7 and 14days of skeletal unloading alter femoral bone and marrow blood flow and vascular resistance during reloading, and 2) whether putative changes in bone perfusion are associated with a gross structural remodeling of the principal nutrient artery (PNA) of the femur. Six-month old male Sprague-Dawley rats were assigned to 7-d or 14-d hindlimb unloading (HU) or weight-bearing control groups. Bone perfusion was measured following 10min of standing (reloading) following the unloading treatment. Histomorphometry was used to determine PNA media wall thickness and maximal diameter. Bone blood flow, arterial pressure and PNA structural characteristics were used to calculate arterial shear stress and circumferential wall stress. During reloading, femoral perfusion was lower in the distal metaphyseal region of 7-d HU rats, and in the proximal and distal metaphyses, diaphysis and diaphyseal marrow of 14-d HU animals relative to that in control rats. Vascular resistance was also higher in all regions of the femur in 14-d HU rats during reloading relative to control animals. Intraluminal diameter of PNAs from 14-d HU rats (138±5μm) was smaller than that of control PNAs (162±6μm), and medial wall thickness was thinner in PNAs from 14-d HU (14.3±0.6μm) versus that of control (18.0±0.8μm) rats. Decreases in both shear stress and circumferential stress occurred in the PNA with HU that later returned to control levels with the reductions in PNA maximal diameter and wall thickness, respectively. The results demonstrate that chronic skeletal unloading attenuates the ability to increase blood flow and nutrient delivery to bone and marrow with immediate acute reloading due, in part, to a remodeling of the bone resistance vasculature. © 2013.

  6. Rat soleus muscle satellite cells during the recovery after gravitational unloading (United States)

    Turtikova, Olga; Shenkman, Boris; Altaeva, Erzhena; Leinsoo, Toomas

    In this study the attempt was made to assess alterations of rat soleus satellite cell (SC) population during muscle regrowth after 14-day gravitational unloading (using the hindlimb suspension model). Myofiber size increases during the recovery period. SCs are supposed to participate in muscle growth by fusion with myofibers and supplying them with new myonuclei [Mitchell PO, Pavlath GK, 2001; Oishi Y., 2008]. Other points of view are known about SC participation in the recovery of atrophied muscle mass during the readaptation period [Bruusgaard J.C. et al., 2011; Jackson JR et al., 2012]. After 2 weeks of hindlimb suspension mki67 expression was fivefold lower as compared to control animals and increased gradually up to 28 times by the day 7 of reloading. Cdh15 was decreased after hindlimb unloading and rose from the 1st day of reloading. The expression reached control level to the day 7th of reloading. Cellular response was going on concurrently with the spike of IGF-1 blood level and the increase in muscle IGF-1 concentration. It is possible that in the early days of reloading period differentiation and fusion of satellite cells which were active by the end of hindlimb suspension occurred. Satellite cell incorporation was assessed by counting the amount of BrdU+ myonuclei under myofiber dystrophin layer. It came more intensively in the 1st day of readaptation. It is in accordance with the 4,5 time increase in myogenin expression as compared to hindlimb suspended animals detected at the same time point. Myogenin expression 3 fold decreased by 3rd day of readaptation. We observed only the tendency of resizing but no significant changes in in myonuclear domain size. The number of myonuclei per myofiber cross section was decreased after hindlimb suspension and was not restored by the day 14th of readaptation. Cdh15 and myogenin expression at some extent stabilized after 7 days of readaptation, but high mki67 level pointed to intensive proliferation, which could

  7. Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting (United States)

    Allen, D. L.; Linderman, J. K.; Roy, R. R.; Bigbee, A. J.; Grindeland, R. E.; Mukku, V.; Edgerton, V. R.


    The role of apoptosis in the elimination of myonuclei during hindlimb unloading-induced atrophy and the inhibition of apoptosis in the prevention of muscle atrophy were examined. The number of nuclei demonstrating double-stranded DNA fragmentation seen by terminal deoxynucleotidyl transferase (TDT) histochemical staining, an indicator of apoptosis, was significantly increased after 14 days of suspension. Double staining with TDT and antilaminin immunohistochemistry revealed that some TDT-positive nuclei were within the fiber lamina and were most likely myonuclei. The number of fibers containing morphologically abnormal nuclei was also significantly greater in suspended compared with control rats. Combined treatment with growth hormone and insulin-like growth factor I (GH/ IGF-I) and resistance exercise attenuated the increase in TDT-positive nuclei (approximately 26%, P > 0.05) and significantly decreased the number of fibers with morphologically abnormal nuclei. The data suggest that 1) "programmed nuclear death" contributes to the elimination of myonuclei and/or satellite cells from atrophying fibers, and 2) GH/IGF-I administration plus muscle loading ameliorates the apoptosis associated with hindlimb unloading.

  8. The effect of unloading and reloading on the extracellular matrix in skeletal muscle: changes in muscle strength and motor activity

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    TES Takala


    Full Text Available During three weeks of hindlimb suspension muscle mass decreased 36%(p<0.05 in Soleus (Sol muscle, 17%(p<0.05 in Gastrocnemius (GM and had tendences to decrease in plantaris (Pla (15% and in extensor digitorum longus (EDL (8% muscles. Hindlimb grip strength decreased gradually during three weeks of unloading. Specific mRNA level for type I collagen decreased during three weeks of unloading in Sol muscle by 28%(p<0.05 and in GM muscle by 34%(p<0.05. mRNA level for type III collagen decreased in Sol by 22%(p<0.05 and in GM by 51%(p<0.001. Non-fibrillar type IV collagen mRNA level decreased in both above-described muscles about 25%(p<0.05. Lysyl oxidase (LO mRNA level decreased by 46%(p<0.05 during three weeks of unloading only in Sol muscle. Matrix metalloproteinase-2 (MMP-2 mRNA level increased during reloading period in Sol and GM muscles subsequently 28%(p<0.05 and 49%(p<0.001. During unloading the activity of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2 in slow-twitch (ST and fast-twitch (FT muscles changed in different directions: during first week of suspension, their expression decreased in Sol muscle by 31%(p<0.05 and increased in Pla and GM muscle subsequently by 24%(p<0.05 and 31%(p<0.001. The pretranslational level of changes in fibrillar and non-fibrillar collagen, MMP-2, LO, TIMP-1 and TIMP-2 -are shown for first time together with changes in muscle strength and motor activity during unloading and reloading

  9. Growth hormone plus resistance exercise attenuate structural changes in rat myotendinous junctions resulting from chronic unloading

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    D. Curzi


    Full Text Available Myotendinous junctions (MTJs are specialized sites on the muscle surface where forces generated by myofibrils are transmitted across the sarcolemma to the extracellular matrix. At the ultrastructural level, the interface between the sarcolemma and extracellular matrix is highly folded and interdigitated at these junctions. In this study, the effect of exercise and growth hormone (GH treatments on the changes in MTJ structure that occur during muscle unloading, has been analyzed. Twenty hypophysectomized rats were assigned randomly to one of five groups: ambulatory control, hindlimb unloaded, hindlimb unloaded plus exercise (3 daily bouts of 10 climbs up a ladder with 50% body wt attached to the tail, hindlimb unloaded plus GH (2 daily injections of 1 mg/kg body wt, i.p., and hindlimb unloaded plus exercise plus GH. MTJs of the plantaris muscle were analyzed by electron microscopy and the contact between muscle and tendon was evaluated using an IL/B ratio, where B is the base and IL is the interface length of MTJ’s digit-like processes. After 10 days of unloading, the mean IL/B ratio was significantly lower in unloaded (3.92, unloaded plus exercise (4.18, and unloaded plus GH (5.25 groups than in the ambulatory control (6.39 group. On the opposite, the mean IL/B ratio in the group treated with both exercise and GH (7.3 was similar to control. These findings indicate that the interaction between exercise and GH treatments attenuates the changes in MTJ structure that result from chronic unloading and thus can be used as a countermeasure to these adaptations.

  10. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats (United States)

    Steffen, J. M.; Musacchia, X. J.


    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  11. FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension

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    Gerrard Dave


    Full Text Available Abstract Background Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. The mechanisms by which unloading of muscle is sensed and translated into signals controlling tissue reduction remains a major question in the field of musculoskeletal research. While the fibroblast growth factors (FGFs and their receptors are synthesized by, and intimately involved in, embryonic skeletal muscle growth and repair, their role maintaining adult muscle status has not been examined. Methods We examined the effects of ectopic expression of FGFR1 during disuse-mediated skeletal muscle atrophy, utilizing hindlimb suspension and DNA electroporation in mice. Results We found skeletal muscle FGF4 and FGFR1 mRNA expression to be modified by hind limb suspension,. In addition, we found FGFR1 protein localized in muscle fibers within atrophying mouse muscle which appeared to be resistant to atrophy. Electroporation and ectopic expression of FGFR1 significantly inhibited the decrease in muscle fiber area within skeletal muscles of mice undergoing suspension induced muscle atrophy. Ectopic FGFR1 expression in muscle also significantly stimulated protein synthesis in muscle fibers, and increased protein degradation in weight bearing muscle fibers. Conclusion These results support the theory that FGF signaling can play a role in regulation of postnatal skeletal muscle maintenance, and could offer potentially novel and efficient therapeutic options for attenuating muscle atrophy during aging, illness and spaceflight.

  12. Effects of skeletal unloading on the vasomotor properties of the rat femur principal nutrient artery. (United States)

    Prisby, Rhonda D; Behnke, Bradley J; Allen, Matthew R; Delp, Michael D


    Spaceflight and prolonged bed rest induce deconditioning of the cardiovascular system and bone loss. Previous research has shown declines in femoral bone and marrow perfusion during unloading and with subsequent reloading in hindlimb-unloaded (HU) rats, an animal model of chronic disuse. We hypothesized that the attenuated bone and marrow perfusion may result from altered vasomotor properties of the bone resistance vasculature. Therefore, the purpose of this study was to determine the effects of unloading on the vasoconstrictor and vasodilator properties of the femoral principal nutrient artery (PNA), the main conduit for blood flow to the femur, in 2 wk HU and control (CON) rats. Vasoconstriction of the femoral PNA was assessed in vitro using norepinephrine, phenylephrine, clonidine, KCl, endothelin-1, arginine vasopressin, and myogenic responsiveness. Vasodilation through endothelium-dependent [acetylcholine, bradykinin, and flow-mediated dilation (FMD)] and endothelium-independent mechanisms [sodium nitroprusside (SNP) and adenosine] were also determined. Vasoconstrictor responsiveness of the PNA from HU rats was not enhanced through any of the mechanisms tested. Endothelium-dependent vasodilation to acetylcholine (CON, 86 ± 3%; HU, 48 ± 7% vasodilation) and FMD (CON, 61 ± 9%; HU, 11 ± 11% vasodilation) were attenuated in PNAs from HU rats, while responses to bradykinin were not different between groups. Endothelium-independent vasodilation to SNP and adenosine were not different between groups. These data indicate that unloading-induced decrements in bone and marrow perfusion and increases in vascular resistance are not the result of enhanced vasoconstrictor responsiveness of the bone resistance arteries but are associated with reductions in endothelium-dependent vasodilation. Copyright © 2015 the American Physiological Society.

  13. Bone Proteoglycan Changes During Skeletal Unloading (United States)

    Yamauchi, M.; Uzawa, K.; Pornprasertsuk, S.; Arnaud, S.; Grindeland, R.; Grzesik, W.


    Skeletal adaptability to mechanical loads is well known since the last century. Disuse osteopenia due to the microgravity environment is one of the major concerns for space travelers. Several studies have indicated that a retardation of the mineralization process and a delay in matrix maturation occur during the space flight. Mineralizing fibrillar type I collagen possesses distinct cross-linking chemistries and their dynamic changes during mineralization correlate well with its function as a mineral organizer. Our previous studies suggested that a certain group of matrix proteoglycans in bone play an inhibitory role in the mineralization process through their interaction with collagen. Based on these studies, we hypothesized that the altered mineralization during spaceflight is due in part to changes in matrix components secreted by cells in response to microgravity. In this study, we employed hindlimb elevation (tail suspension) rat model to study the effects of skeletal unloading on matrix proteoglycans in bone.

  14. Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy (United States)

    Criswell, D. S.; Booth, F. W.; DeMayo, F.; Schwartz, R. J.; Gordon, S. E.; Fiorotto, M. L.


    This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced (P muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.

  15. CD44 deficiency inhibits unloading-induced cortical bone loss through downregulation of osteoclast activity. (United States)

    Li, Yuheng; Zhong, Guohui; Sun, Weijia; Zhao, Chengyang; Zhang, Pengfei; Song, Jinping; Zhao, Dingsheng; Jin, Xiaoyan; Li, Qi; Ling, Shukuan; Li, Yingxian


    The CD44 is cellular surface adhesion molecule that is involved in physiological processes such as hematopoiesis, lymphocyte homing and limb development. It plays an important role in a variety of cellular functions including adhesion, migration, invasion and survival. In bone tissue, CD44 is widely expressed in osteoblasts, osteoclasts and osteocytes. However, the mechanisms underlying its role in bone metabolism remain unclear. We found that CD44 expression was upregulated during osteoclastogenesis. CD44 deficiency in vitro significantly inhibited osteoclast activity and function by regulating the NF-κB/NFATc1-mediated pathway. In vivo, CD44 mRNA levels were significantly upregulated in osteoclasts isolated from the hindlimb of tail-suspended mice. CD44 deficiency can reduce osteoclast activity and counteract cortical bone loss in the hindlimb of unloaded mice. These results suggest that therapeutic inhibition of CD44 may protect from unloading induced bone loss by inhibiting osteoclast activity.

  16. Preserved gait kinematics during controlled body unloading. (United States)

    Awai, L; Franz, M; Easthope, C S; Vallery, H; Curt, A; Bolliger, M


    Body weight supported locomotor training was shown to improve walking function in neurological patients and is often performed on a treadmill. However, walking on a treadmill does not mimic natural walking for several reasons: absent self-initiation, less active retraction of leg required and altered afferent input. The superiority of overground training has been suggested in humans and was shown in rats demonstrating greater plasticity especially in descending pathways compared to treadmill training. We therefore developed a body weight support system allowing unrestricted overground walking with minimal interfering forces to train neurological patients. The present study investigated the influence of different amounts of body weight support on gait in healthy individuals. Kinematic and electromyographic data of 19 healthy individuals were recorded during overground walking at different levels of body weight support (0, 10, 20, 30, 40, and 50%). Upper body inclination, lower body joint angles and multi-joint coordination as well as time-distance parameters were calculated. Continuous data were analyzed with regard to distinct changes within a gait cycle across all unloading conditions. Temporal gait parameters were most sensitive to changes in body unloading while spatial variables (step length, joint angles) showed modest responses when unloaded by as much as 50% body weight. The activation of the gastrocnemius muscle showed a gradual decrease with increasing unloading while the biceps femoris muscle showed increased activity levels at 50% unloading. These changes occurred during stance phase while swing phase activity remained unaltered. Healthy individuals were able to keep their walking kinematics strikingly constant even when unloaded by half of their body weight, suggesting that the weight support system permits a physiological gait pattern. However, maintaining a given walking speed using close-to-normal kinematics while being unloaded was achieved by

  17. Osteophytes and fracture calluses share developmental milestones and are diminished by unloading. (United States)

    Hsia, Allison W; Emami, Armaun J; Tarke, Franklin D; Cunningham, Hailey C; Tjandra, Priscilla M; Wong, Alice; Christiansen, Blaine A; Collette, Nicole M


    Osteophytes are a typical radiographic finding during osteoarthritis (OA), but the mechanisms leading to their formation are not well known. Comparatively, fracture calluses have been studied extensively; therefore, drawing comparisons between osteophytes and fracture calluses may lead to a deeper understanding of osteophyte formation. In this study, we compared the time courses of osteophyte and fracture callus formation, and investigated mechanisms contributing to development of these structure. Additionally, we investigated the effect of mechanical unloading on the formation of both fracture calluses and osteophytes. Mice underwent either transverse femoral fracture or non-invasive anterior cruciate ligament rupture. Fracture callus and osteophyte size and ossification were evaluated after 3, 5, 7, 14, 21, or 28 days. Additional mice were subjected to hindlimb unloading after injury for 3, 7, or 14 days. Protease activity and gene expression profiles after injury were evaluated after 3 or 7 days of normal ambulation or hindlimb unloading using in vivo fluorescence reflectance imaging (FRI) and quantitative PCR. We found that fracture callus and osteophyte growth achieved similar developmental milestones, but fracture calluses formed and ossified at earlier time points. Hindlimb unloading ultimately led to a threefold decrease in chondro/osteophyte area, and a twofold decrease in fracture callus area. Unloading was also associated with decreased inflammation and protease activity in injured limbs detected with FRI, particularly following ACL rupture. qPCR analysis revealed disparate cellular responses in fractured femurs and injured joints, suggesting that fracture calluses and osteophytes may form via different inflammatory, anabolic, and catabolic pathways. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Changes in ?B-crystallin, tubulin, and MHC isoforms by hindlimb unloading show different expression patterns in various hindlimb muscles


    Jee, Hyunseok; Sakurai, Takashi; Lim, Jae-Young; Hatta, Hideo


    [Purpose] ?B-crystallin is a small heat shock protein that acts as a molecular chaperone under various stress conditions. Microtubules, which consist of tubulin, are related to maintain the intracellular organelles and cellular morphology. These two proteins have been shown to be related to the properties of different types of myofibers based on their contractile properties. The response of these proteins during muscular atrophy, which induces a myofibril component change, is not clearly unde...

  19. [Changes in cell respiration of postural muscle fibers under long-term gravitational unloading after dietary succinate supplementation]. (United States)

    Ogneva, I V; Veselova, O M; Larina, I M


    The intensity of cell respiration of the rat m. soleus, m. gastrocnemius c.m. and tibialis anterior fibers during 35-day gravitational unloading, with the addition of succinate in the diet at a dosage rate of 50 mg per 1 kg animal weight has been investigated. The gravitational unloading was modeled by antiorthostatic hindlimb suspension. The intensity of cell respiration was estimated by polarography. It was shown that the rate of oxygen consumption by soleus and gastrocnemius fibers on endogenous and exogenous substrates and with the addition of ADP decreases after the discharge. This may be associated with the transition to the glycolytic energy path due to a decrease in the EMG-activity. At the same time, the respiration rate after the addition of exogenous substrates in soleus fibers did not increase, indicating a disturbance in the function of the NCCR-section of the respiratory chain and more pronounced changes in the structure of muscle fibers. In tibialis anterior fibers, no changes in oxygen consumption velocity were observed. The introduction of succinate to the diet of rats makes it possible to prevent the negative effects of hypokinesia, although it reduces the basal level of intensity of cell respiration.

  20. Vestibular nucleus neurons respond to hindlimb movement in the decerebrate cat. (United States)

    Arshian, Milad S; Hobson, Candace E; Catanzaro, Michael F; Miller, Daniel J; Puterbaugh, Sonya R; Cotter, Lucy A; Yates, Bill J; McCall, Andrew A


    The vestibular nuclei integrate information from vestibular and proprioceptive afferents, which presumably facilitates the maintenance of stable balance and posture. However, little is currently known about the processing of sensory signals from the limbs by vestibular nucleus neurons. This study tested the hypothesis that limb movement is encoded by vestibular nucleus neurons and described the changes in activity of these neurons elicited by limb extension and flexion. In decerebrate cats, we recorded the activity of 70 vestibular nucleus neurons whose activity was modulated by limb movements. Most of these neurons (57/70, 81.4%) encoded information about the direction of hindlimb movement, while the remaining neurons (13/70, 18.6%) encoded the presence of hindlimb movement without signaling the direction of movement. The activity of many vestibular nucleus neurons that responded to limb movement was also modulated by rotating the animal's body in vertical planes, suggesting that the neurons integrated hindlimb and labyrinthine inputs. Neurons whose firing rate increased during ipsilateral ear-down roll rotations tended to be excited by hindlimb flexion, whereas neurons whose firing rate increased during contralateral ear-down tilts were excited by hindlimb extension. These observations suggest that there is a purposeful mapping of hindlimb inputs onto vestibular nucleus neurons, such that integration of hindlimb and labyrinthine inputs to the neurons is functionally relevant. Copyright © 2014 the American Physiological Society.

  1. Interplay Between Aging and Unloading on Oxidative Stress in Fast-Twitch Muscles (United States)


    This study evaluated the effect of aging on the adaptation potential of antioxidants and the accumulation of oxidative damage in fast-twitch muscles in response to non–weight-bearing conditions. Adult and old rats were randomized into 4 groups: normal weight bearing, hind-limb unloading for 3, 7, and 14 days. Activities of manganese superoxide dismutase, copper–zinc superoxide dismutase, catalase, and glutathione peroxidase and contents of glutathione, carbonylated proteins, and malondialdehyde were determined in tibialis anterior muscles. We found that the adaptability of most antioxidants in fast-twitch muscles with unloading is intact in aged rats except copper–zinc superoxide dismutase where its activity decreased with 14 days of unloading. Additionally, malondialdehyde accumulated in aged muscles with 14 days of unloading but not adult muscles. Collectively, the adaptation of copper–zinc superoxide dismutase in fast-twitch muscles with unloading is impaired with aging, which may be related to the greater accumulation of malondialdehyde. PMID:23213028

  2. l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats. (United States)

    Jang, Jiwoong; Park, Jonghoon; Chang, Hyukki; Lim, Kiwon


    l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg -1 ·day -1 ) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

  3. Current state of unloading braces for knee osteoarthritis. (United States)

    Steadman, J Richard; Briggs, Karen K; Pomeroy, Shannon M; Wijdicks, Coen A


    Unicompartmental knee osteoarthritis (OA) is often treated with the prescription of an unloading knee brace to decrease pain and stiffness. Braces have been shown to improve the quality of life by applying an external moment to offset increased compressive tibiofemoral contact loads, but evidence regarding mechanical efficacy at the joint is controversial. Thus, the purpose of this study was to review the current state of unloading braces on knee mechanics, clinical impact, and long-term disease progression. A literature search was performed through the PubMed MEDLINE database for the search terms "osteoarthritis," "knee," "brace," and derivatives of the keyword "unload." Articles published since January 1, 1980 were reviewed for their relevance. Evidence for the effectiveness of unloading braces for disease management both biomechanically and clinically was considered. While significant research has been done to show improvement in OA symptoms with the use of an unloading brace, current literature suggests a debate regarding the effectiveness of these braces for biomechanical change. Clinical findings reveal overall improvements in parameters such as pain, instability, and quality of life. Although clinical evidence supports brace use to improve pain and functional ability, current biomechanical evidence suggests that unloading of the affected knee compartment does not significantly hinder disease progression. III.

  4. Force-velocity and power characteristics of rat soleus muscle fibers after hindlimb suspension (United States)

    Mcdonald, K. S.; Blaser, C. A.; Fitts, R. H.


    The effects of 1, 2, and 3 wk of hindlimb suspension (HS) on force-velocity and power characteristics of single rat soleus fibers were determined. After 1, 2, or 3 wk of HA, small fiber bundles were isolated, placed in skinning solution, and stored at -20 C until studied. Single fibers were isolated and placed between a motor arm and force transducer, functional properties were studied, and fiber protein content was subsequently analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Additional fibers were isolated from soleus of control after 1 and 3 wk of HS, and fiber type distribution and myosin light chain stoichiometry were determined from SDS-PAGE analysis. After 1 wk of HS, percent type I fibers declined from 82 to 74%, whereas hybrid fibers increased from 10 to 18%. Percent fast type II fibers increased from 8% in control and 1 wk of HS to 26% by 3 wk of HS. Most fibers showed an increased unloaded maximal shortening velocity (V sub O)), but myosin heavy chain remained entirely slow type I. The mechanism for increased V(sub O) is unknown. There was a progressive decrease in fiber diameter and peak force after 1, 2, and 3 wk of HS, respectively. One week of HS resulted in a shift of the force-velocity curve, and between 2 and 3 wk of HS the curve shifted further such that V(sub O) was higher than control at all relative loads less than 45% peak isometric force. Peak absolute power output of soleus fibers progressively decreased through 2 wk of HS but showed no further change at 3 wk. The results suggest that between 2 and 3 wk the HS-induced alterations in the force-velocity relationship act to maintain the power output of single soleus fibers despite a continued reduction in fiber force.

  5. Time-Course of Muscle Mass Loss, Damage, and Proteolysis in Gastrocnemius following Unloading and Reloading: Implications in Chronic Diseases.

    Directory of Open Access Journals (Sweden)

    Alba Chacon-Cabrera

    Full Text Available Disuse muscle atrophy is a major comorbidity in patients with chronic diseases including cancer. We sought to explore the kinetics of molecular mechanisms shown to be involved in muscle mass loss throughout time in a mouse model of disuse muscle atrophy and recovery following immobilization.Body and muscle weights, grip strength, muscle phenotype (fiber type composition and morphometry and muscle structural alterations, proteolysis, contractile proteins, systemic troponin I, and mitochondrial content were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days of non-invasive hindlimb immobilization (plastic splint, I cohorts and in those exposed to reloading for different time-points (1, 3, 7, 15, and 30 days, R cohorts following a seven-day period of immobilization. Groups of control animals were also used.Compared to non-exposed controls, muscle weight, limb strength, slow- and fast-twitch cross-sectional areas, mtDNA/nDNA, and myosin content were decreased in mice of I cohorts, whereas tyrosine release, ubiquitin-proteasome activity, muscle injury and systemic troponin I levels were increased. Gastrocnemius reloading following splint removal improved muscle mass loss, strength, fiber atrophy, injury, myosin content, and mtDNA/nDNA, while reducing ubiquitin-proteasome activity and proteolysis.A consistent program of molecular and cellular events leading to reduced gastrocnemius muscle mass and mitochondrial content and reduced strength, enhanced proteolysis, and injury, was seen in this non-invasive mouse model of disuse muscle atrophy. Unloading of the muscle following removal of the splint significantly improved the alterations seen during unloading, characterized by a specific kinetic profile of molecular events involved in muscle regeneration. These findings have implications in patients with chronic diseases including cancer in whom physical activity may be severely compromised.

  6. Modification of a Rodent Hindlimb Model of Secondary Lymphedema: Surgical Radicality versus Radiotherapeutic Ablation

    Directory of Open Access Journals (Sweden)

    Hyung Sub Park


    Full Text Available Secondary lymphedema is an intractable disease mainly caused by damage of the lymphatic system during surgery, yet studies are limited by the lack of suitable animal models. The purpose of this study was to create an improved model of secondary lymphedema in the hindlimbs of rodents with sustained effects and able to mimic human lymphedema. This was achieved by combining previously reported surgical methods and radiation to induce chronic lymphedema. Despite more radical surgical destruction of superficial and deep lymphatic vessels, surgery alone was not enough to sustain increased hindlimb volume. Radiotherapy was necessary to prolong these effects, with decreased lymphatic flow on lymphoscintigraphy, but hindlimb necrosis occurred after 4 weeks due to radiation toxicity. The applicability of this model for studies of therapeutic lymphangiogenesis was subsequently tested by injecting muscle-derived stem cells previously cocultured with the supernatant of human lymphatic endothelial cells in vitro. There was a tendency for increased lymphatic flow which significantly increased lymphatic vessel formation after cell injection, but attenuation of hindlimb volume was not observed. These results suggest that further refinement of the rodent hindlimb model is needed by titration of adequate radiation dosage, while stem cell lymphangiogenesis seems to be a promising approach.

  7. Lymph Drainage During Wound Healing in a Hindlimb Lymphedema Mouse Model. (United States)

    Komatsu, Emi; Nakajima, Yukari; Mukai, Kanae; Urai, Tamae; Asano, Kimi; Okuwa, Mayumi; Sugama, Junko; Nakatani, Toshio


    Although lymphedematous skin exhibits delayed wound healing, little is known about lymph drainage during wound healing. We investigated the wound healing process in the presence of lymphatic dysfunction. The right inguinal lymph nodes (iLNs) and the surrounding tissue were excised in each mouse (the operation side), and a sham operation was performed in the left hindlimb (the control side). The next day, full-thickness wounds were made on both hindlimbs. The right hindlimb exhibited acute edema until day 3; however, it started to improve after day 4, and the wound area and epithelialization ratio were similar on both sides. Indocyanine green (ICG) was injected into both hindlimbs to observe lymph flow. On the operation side, ICG leaked out of the surgical site or remained at the injection site until day 2. Some lymph flow toward the existing lymph vessels was seen on day 3, and on day 10, lymph flow toward the axial LNs was detected on the operation side in all mice. On the operation side, the number of dermal lymph vessels was significantly increased on days 3 and 15. The dermal lymph vessel area of the peripheral wound was significantly smaller on the operation side. In a hindlimb lymphedema mouse model, lymph transiently accumulated in subcutaneous tissue, and then was gradually absorbed by the existing lymph vessels. The increase in the number of lymph vessels contributes to lymph drainage during wound healing. Acute lymphedema because of transient lymphatic dysfunction has little effect on wound healing.

  8. Vulnerability to dysfunction and muscle injury after unloading (United States)

    Ploutz-Snyder, L. L.; Tesch, P. A.; Hather, B. M.; Dudley, G. A.


    OBJECTIVE: To test whether unloading increases vulnerability to eccentric exercise-induced dysfunction and muscle injury. DESIGN: Before-after trial. SETTING: General community. PATIENTS OR OTHER PARTICIPANTS: Two women and 5 men (73 +/- 3kg [mean +/- SE]) who were active college students but were not trained in lower body resistance exercise volunteered. INTERVENTION: Five weeks of unilateral lower limb suspension (ULLS), which has been shown to decrease strength and size of the unloaded, left, but not load-bearing, right quadriceps femoris muscle group (QF) by 20% and 14%, respectively; performance of 10 sets of ten eccentric actions with each QF immediately after the ULLS strength tests with a load equivalent to 65% of the post-ULLS eccentric 1-repetition maximum. MAIN OUTCOME MEASURE(S): Concentric and eccentric 1-repetition maximum for the left, unloaded and the right, load-bearing QF measured immediately after ULLS and 1,4,7,9, and 11 days later; cross-sectional area and spin-spin relaxation time (T2) of each QF as determined by magnetic resonance imaging and measured the last day of ULLS and 3 days later. RESULTS: The mean load used for eccentric exercise was 23 +/- 2 and 30 +/- 3kg for the left, unloaded and right, load-bearing QF, respectively. The concentric and eccentric 1-repetition maximum for the unloaded and already weakened left QF was further decreased by 18% (p = .000) and 27% (p = .000), respectively, 1 day after eccentric exercise. Strength did not return to post-ULLS levels until 7 days of recovery. The right, load-bearing QF showed a 4% decrease (p = .002) in the eccentric 1-repetition maximum 1 day after eccentric exercise. The left, unloaded QF showed an increase in T2 (p = .002) in 18% of its cross-sectional area 3 days after the eccentric exercise, thus indicating muscle injury. The right, load-bearing QF showed no elevation in T2 (p = .280). CONCLUSION: Unloading increases vulnerability to eccentric exercise-induced dysfunction and muscle

  9. Excitability changes in sacral afferents innervating the urethra, perineum and hindlimb skin of the cat during micturition (United States)

    Buss, R R; Shefchyk, S J


    Excitability changes in afferents innervating the urethra, perineum and hindlimb were measured in decerebrated cats during micturition and in response to stimulation of lumbosacral afferents. Increases in excitability were interpreted as primary afferent depolarization (PAD) and decreases as primary afferent hyperpolarization.Excitability increases were observed in 11 of 19 urethral pudendal afferents during micturition. Four of these 11 afferents showed an excitability increase during voiding. Seven of these showed a biphasic change with a decrease in excitability when sphincter activity resumed at the end of the void. Three of 19 afferents showed an excitability decrease during micturition and no change was detected in five afferents.During micturition, the peak amplitude of urethral afferent-evoked excitatory postsynaptic potentials in seven of eight sphincter motoneurones was diminished to a mean of 36% of control values.Eighty per cent of hindlimb cutaneous afferents and 50% of dorsal penile/clitoral and superficial perineal nerve afferents in the sacral cord showed increased excitability during voiding. No excitability increases were measured in 13 hindlimb cutaneous fibres examined in the lumbar segments.PAD was observed in sacral urethral, perineal and hindlimb cutaneous afferents in response to electrical stimulation of other perineal, urethral, hindlimb cutaneous and group II muscle afferents.It is concluded that control of transmission from urethral afferents by the micturition circuitry is different to that by sensory transmission from hindlimb and perineal regions during micturition. We hypothesize that more than one population of sacral PAD-mediating interneurones is involved. PMID:9852338

  10. Comparative hindlimb myology of foot-propelled swimming birds. (United States)

    Clifton, Glenna T; Carr, Jennifer A; Biewener, Andrew A


    Several groups of birds have convergently evolved the ability to swim using their feet despite facing trade-offs with walking. However, swimming relative to terrestrial performance varies across these groups. Highly specialized divers, such as loons and grebes, excel at swimming underwater but struggle to stand on land, whereas species that primarily swim on the water surface, such as Mallards, retain the ability to move terrestrially. The identification of skeletal features associated with a swimming style and conserved across independent groups suggests that the hindlimb of foot-propelled swimming birds has adapted to suit the physical challenges of producing propulsive forces underwater. But in addition to skeletal features, how do hindlimb muscles reflect swimming ability and mode? This paper presents the first comparative myology analysis associated with foot-based swimming. Our detailed dissections of 35 specimens representing eight species reveal trends in hindlimb muscle size and attachment location across four independent lineages of extant swimming birds. We expand upon our dissections by compiling data from historical texts and provide a key to any outdated muscle nomenclature used in these sources. Our results show that highly diving birds tuck the femur and proximal tibiotarsus next to the ribcage and under the skin covering the abdomen, streamlining the body. Several hindlimb muscles exhibit dramatic anatomical variation in diving birds, including the flexor cruris lateralis (FCL) and iliofibularis (IF), which reduce in size and shift distally along the tibiotarsus. The femorotibialis medius (FTM) extends along an expanded cnemial crest. The resulting increased moment arms of these muscles likely help stabilize the hip and knee while paddling. Additionally, distal ankle plantarflexors, including the gastrocnemius and digital flexors, are exceptionally large in diving birds in order to power foot propulsion. These patterns exist within distantly

  11. Properties of primary motor cortex output to hindlimb muscles in the macaque monkey (United States)

    Hudson, Heather M.; Griffin, Darcy M.; Belhaj-Saïf, Abderraouf


    The cortical control of forelimb motor function has been studied extensively, especially in the primate. In contrast, cortical control of the hindlimb has been relatively neglected. This study assessed the output properties of the primary motor cortex (M1) hindlimb representation in terms of the sign, latency, magnitude, and distribution of effects in stimulus-triggered averages (StTAs) of electromyography (EMG) activity recorded from 19 muscles, including hip, knee, ankle, digit, and intrinsic foot muscles, during a push-pull task compared with data reported previously on the forelimb. StTAs (15, 30, and 60 μA at 15 Hz) of EMG activity were computed at 317 putative layer V sites in two rhesus macaques. Poststimulus facilitation (PStF) was distributed equally between distal and proximal muscles, whereas poststimulus suppression (PStS) was more common in distal muscles than proximal muscles (51/49%, respectively, for PStF; 72/28%, respectively, for PStS) at 30 μA. Mean PStF and PStS onset latency generally increased the more distal the joint of a muscle's action. Most significantly, the average magnitude of hindlimb poststimulus effects was considerably weaker than the average magnitude of effects from forelimb M1. In addition, forelimb PStF magnitude increased consistently from proximal to distal joints, whereas hindlimb PStF magnitude was similar at all joints except the intrinsic foot muscles, which had a magnitude of approximately double that of all of the other muscles. The results suggest a greater monosynaptic input to forelimb compared with hindlimb motoneurons, as well as a more direct synaptic linkage for the intrinsic foot muscles compared with the other hindlimb muscles. PMID:25411454

  12. Effect of trotting speed, load and incline on hindlimb stance-phase kinematics. (United States)

    Hoyt, D F; Molinari, M; Wickler, S J; Cogger, E A


    The objective was to understand how the stance-phase kinematics of the hindlimb of trotting horses change with speed under 3 conditions (level, loaded and incline), to compare our results with the predictions of the spring-mass model and to help focus our future studies of muscle function. Video recordings were made of 5 Arabian horses trotting on a treadmill. Five consecutive strides were digitised and averaged for each trial. The angle-time diagrams were qualitatively similar to those reported previously. As speed increases, the range of motion of the hindlimb increases, as predicted by the spring-mass model. This is the result of increased range of motion in the coxofemoral and tarsal joints. The hindlimb does not 'land short-take off long'. When trotting up an incline, the hindlimb undergoes a greater range of motion because of increased retraction resulting from increased extension of the coxofemoral joint. At hoof contact on an incline, the 3 proximal joints are more flexed than on the level. Carrying a load had no effect on kinematics. These results suggest that there may be larger changes in strain with speed in muscles acting at the coxofemoral and tarsal joints than at the femorotibial joint, and that locomotion up an incline will change muscle strain more than carrying a load.

  13. Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia (United States)

    Musacchia, X. J.; Steffen, J. M.; Deavers, D. R.


    Hypokinetic/hyupodynamic (H/H) whole body suspension of rats eliminates hindlimb load bearing functions while permitting continued use of the forelimbs. Responses of hindlimb muscles were assessed in terms of absolute and relative weights during 1 and 2 weeks of H/H suspension. Muscle mass loss was in the order soleus greater than gastrocnemius equal to plantaris greater than extensor digitorum longus (EDL). The soleus, a postural antigravity muscle composed mainly of slow twitch fibers, was most sensitive, losing 35 and 45 percent of its weight during the first and second weeks, respectively. The gastrocnemius and plantaris showed losses during the first week but no significant loss during the second wee. The EDL showed little or no weight loss. During post suspension recovery all muscles showed a weight gain. H/H suspended rats failed to grow; following removal from suspension they gained weight linearly, comparable to controls. Products of muscle metabolism including urea, ammonia, and 3-methylhistidine increased in the urine during H/H suspension and were significantly reduced approaching control levels during recovery. This suspension model offers considerable promise for comparison with H/H responses during weightlessness.

  14. Influence of mechanical unloading on histological changes of the patellar tendon insertion in rabbits. (United States)

    Mutsuzaki, Hirotaka; Nakajima, Hiromi; Wadano, Yasuyoshi; Takahashi, Hikaru; Sakane, Masataka


    The purpose of this study was to clarify the influence of mechanical unloading on histological changes of the patellar tendon (PT) insertion in rabbits. The PT was completely released from stress by drawing the patella toward the tibial tubercle with a stainless steel wire installed between the patella and tibial tubercle (mechanical unloading group, n=28). The animals of the sham group underwent the same surgical procedure; however, the wire was not tightened (n=28). The average thickness of the Safranin O-stained glycosaminoglycan (GAG) area, chondrocyte apoptosis rate and chondrocyte proliferation rate of the cartilage layer at the insertion were measured at one, two, four, and six weeks. The chondrocyte apoptosis rate in the mechanical unloading group was significantly higher than that in the sham group at one and four weeks (pmechanical unloading group was significantly lower than that in the sham group at four and six weeks (pmechanical unloading group was significantly lower than that in the sham group at six weeks (pMechanical unloading significantly affected the increase in the chondrocyte apoptosis rate, decrease in the chondrocyte proliferation rate, and decrease in the GAG layer thickness at the PT insertion for up to six weeks in rabbits. We suggest that more than 6 weeks of mechanical unloading should be avoided to prevent degeneration at the PT insertion. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Vasopressin and angiotensin II stimulate oxygen uptake in the perfused rat hindlimb

    DEFF Research Database (Denmark)

    Colquhoun, E Q; Hettiarachchi, M; Ye, J M


    uptake and pressure were not inhibited by either phentolamine, propranolol or a combination of the two, but were completely inhibited by the vasodilator, nitroprusside. Nitroprusside also inhibited flow-induced increases in hindlimb oxygen uptake and perfusion pressure. The findings indicate a key role...

  16. Bradykinin does not acutely sensitize the reflex pressor response during hindlimb skeletal muscle stretch in decerebrate rats. (United States)

    Rollins, Korynne S; Smith, Joshua R; Esau, Peter J; Kempf, Evan A; Hopkins, Tyler D; Copp, Steven W


    Hindlimb skeletal muscle stretch (i.e., selective activation of the muscle mechanoreflex) in decerebrate rats evokes reflex increases in blood pressure and sympathetic nerve activity. Bradykinin has been found to sensitize mechanogated channels through a bradykinin B2 receptor-dependent mechanism. Moreover, bradykinin B2 receptor expression on sensory neurons is increased following chronic femoral artery ligation in the rat (a model of simulated peripheral artery disease). We tested the hypothesis that injection of bradykinin into the arterial supply of a hindlimb in decerebrate, unanesthetized rats would acutely augment (i.e., sensitize) the increase in blood pressure and renal sympathetic nerve activity during hindlimb muscle stretch to a greater extent in rats with a ligated femoral artery than in rats with a freely perfused femoral artery. The pressor response during static hindlimb muscle stretch was compared before and after hindlimb arterial injection of 0.5 µg of bradykinin. Injection of bradykinin increased blood pressure to a greater extent in "ligated" (n = 10) than "freely perfused" (n = 10) rats. The increase in blood pressure during hindlimb muscle stretch, however, was not different before vs. after bradykinin injection in freely perfused (14 ± 2 and 15 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.62) or ligated (15 ± 3 and 14 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.80) rats. Likewise, the increase in renal sympathetic nerve activity during stretch was not different before vs. after bradykinin injection in either group of rats. We conclude that bradykinin did not acutely sensitize the pressor response during hindlimb skeletal muscle stretch in freely perfused or ligated decerebrate rats. Copyright © 2017 the American Physiological Society.

  17. Anatomy and histochemistry of hindlimb flight posture in birds. I. The extended hindlimb posture of shorebirds. (United States)

    McFarland, Joshua C; Meyers, Ron A


    Birds utilize one of two hindlimb postures during flight: an extended posture (with the hip and knee joints flexed, while the ankle joint is extended caudally) or a flexed posture (with the hip, knee, and ankle joints flexed beneath the body). American Avocets (Recurvirostra americana) and Black-necked Stilts (Himantopus mexicanus) extend their legs caudally during flight and support them for extended periods. Slow tonic and slow twitch muscle fibers are typically found in muscles functioning in postural support due to the fatigue resistance of these fibers. We hypothesized that a set of small muscles composed of high percentages of slow fibers and thus dedicated to postural support would function in securing the legs in the extended posture during flight. This study examined the anatomy and histochemical profile of eleven hindlimb muscles to gain insight into their functional roles during flight. Contrary to our hypothesis, all muscles possessed both fast twitch and slow twitch or slow tonic fibers. We believe this finding is due to the versatility of dynamic and postural functions the leg muscles must facilitate, including standing, walking, running, swimming, and hindlimb support during flight. Whether birds use an extended or flexed hindlimb flight posture may be related to the aerodynamic effect of leg position or may reflect evolutionary history. (c) 2008 Wiley-Liss, Inc.

  18. Mechanical unloading reduces microtubule actin crosslinking factor 1 expression to inhibit β-catenin signaling and osteoblast proliferation. (United States)

    Yin, Chong; Zhang, Yan; Hu, Lifang; Tian, Ye; Chen, Zhihao; Li, Dijie; Zhao, Fan; Su, Peihong; Ma, Xiaoli; Zhang, Ge; Miao, Zhiping; Wang, Liping; Qian, Airong; Xian, Cory J


    Mechanical unloading was considered a major threat to bone homeostasis, and has been shown to decrease osteoblast proliferation although the underlying mechanism is unclear. Microtubule actin crosslinking factor 1 (MACF1) is a cytoskeletal protein that regulates cellular processes and Wnt/β-catenin pathway, an essential signaling pathway for osteoblasts. However, the relationship between MACF1 expression and mechanical unloading, and the function and the associated mechanisms of MACF1 in regulating osteoblast proliferation are unclear. This study investigated effects of mechanical unloading on MACF1 expression levels in cultured MC3T3-E1 osteoblastic cells and in femurs of mice with hind limb unloading; and it also examined the role and potential action mechanisms of MACF1 in osteoblast proliferation in MACF1-knockdown, overexpressed or control MC3T3-E1 cells treated with or without the mechanical unloading condition. Results showed that the mechanical unloading condition inhibited osteoblast proliferation and MACF1 expression in MC3T3-E1 osteoblastic cells and mouse femurs. MACF1 knockdown decreased osteoblast proliferation, while MACF1 overexpression increased it. The inhibitory effect of mechanical unloading on osteoblast proliferation also changed with MACF1 expression levels. Furthermore, MACF1 was found to enhance β-catenin expression and activity, and mechanical unloading decreased β-catenin expression through MACF1. Moreover, β-catenin was found an important regulator of osteoblast proliferation, as its preservation by treatment with its agonist lithium attenuated the inhibitory effects of MACF1-knockdown or mechanical unloading on osteoblast proliferation. Taken together, mechanical unloading decreases MACF1 expression, and MACF1 up-regulates osteoblast proliferation through enhancing β-catenin signaling. This study has thus provided a mechanism for mechanical unloading-induced inhibited osteoblast proliferation. © 2017 Wiley Periodicals, Inc.

  19. Scale effects and morphological diversification in hindlimb segment mass proportions in neognath birds. (United States)

    Kilbourne, Brandon M


    In spite of considerable work on the linear proportions of limbs in amniotes, it remains unknown whether differences in scale effects between proximal and distal limb segments has the potential to influence locomotor costs in amniote lineages and how changes in the mass proportions of limbs have factored into amniote diversification. To broaden our understanding of how the mass proportions of limbs vary within amniote lineages, I collected data on hindlimb segment masses - thigh, shank, pes, tarsometatarsal segment, and digits - from 38 species of neognath birds, one of the most speciose amniote clades. I scaled each of these traits against measures of body size (body mass) and hindlimb size (hindlimb length) to test for departures from isometry. Additionally, I applied two parameters of trait evolution (Pagel's λ and δ) to understand patterns of diversification in hindlimb segment mass in neognaths. All segment masses are positively allometric with body mass. Segment masses are isometric with hindlimb length. When examining scale effects in the neognath subclade Land Birds, segment masses were again positively allometric with body mass; however, shank, pedal, and tarsometatarsal segment masses were also positively allometric with hindlimb length. Methods of branch length scaling to detect phylogenetic signal (i.e., Pagel's λ) and increasing or decreasing rates of trait change over time (i.e., Pagel's δ) suffer from wide confidence intervals, likely due to small sample size and deep divergence times. The scaling of segment masses appears to be more strongly related to the scaling of limb bone mass as opposed to length, and the scaling of hindlimb mass distribution is more a function of scale effects in limb posture than proximo-distal differences in the scaling of limb segment mass. Though negative allometry of segment masses appears to be precluded by the need for mechanically sound limbs, the positive allometry of segment masses relative to body mass may

  20. Regional responsiveness of the tibia to intermittent administration of parathyroid hormone as affected by skeletal unloading (United States)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Tanner, S.; Curren, T.; Morey-Holton, E.


    To determine whether the acute inhibition of bone formation and deficit in bone mineral induced by skeletal unloading can be prevented, we studied the effects of intermittent parathyroid hormone (PTH) administration (8 micrograms/100 g/day) on growing rats submitted to 8 days of skeletal unloading. Loss of weight bearing decreased periosteal bone formation by 34 and 51% at the tibiofibular junction and tibial midshaft, respectively, and reduced the normal gain in tibial mass by 35%. Treatment with PTH of normally loaded and unloaded animals increased mRNA for osteocalcin (+58 and +148%, respectively), cancellous bone volume in the proximal tibia (+41 and +42%, respectively), and bone formation at the tibiofibular junction (+27 and +27%, respectively). Formation was also stimulated at the midshaft in unloaded (+47%, p animals (-3%, NS). Although cancellous bone volume was preserved in PTH-treated, unloaded animals, PTH did not restore periosteal bone formation to normal nor prevent the deficit in overall tibial mass induced by unloading. We conclude that the effects of PTH on bone formation are region specific and load dependent. PTH can prevent the decrease in cancellous bone volume and reduce the decrement in cortical bone formation induced by loss of weight bearing.

  1. Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats (United States)

    Zhao, Fan; Li, Dijie; Arfat, Yasir; Chen, Zhihao; Liu, Zonglin; Lin, Yu; Ding, Chong; Sun, Yulong; Hu, Lifang; Shang, Peng; Qian, Airong


    Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones. After HLU for 4 weeks, the rats were then subjected to reloading for 1 week, 2 weeks and 3 weeks, and then the BMD of the femur, tibia and lumbar spine in rats were assessed by dual energy X-ray absorptiometry (DXA) every week. The mechanical properties of the femur were determined by three-point bending test. Dry bone and bone ash of femur were obtained through Oven-Drying method and were weighed respectively. Serum alkaline phosphatase (ALP) and serum calcium were examined through ELISA and Atomic Absorption Spectrometry. The results showed that 4 weeks of HLU significantly decreased body weight of rats and reloading for 1 week, 2 weeks or 3 weeks did not recover the weight loss induced by HLU. However, after 2 weeks of reloading, BMD of femur and tibia of HLU rats partly recovered (+10.4%, +2.3%). After 3 weeks of reloading, the reduction of BMD, energy absorption, bone mass and mechanical properties of bone induced by HLU recovered to some extent. The changes in serum ALP and serum calcium induced by HLU were also recovered after reloading. Our results indicate that a short period of reloading could not completely recover bone after a period of unloading, thus some interventions such as mechanical vibration or pharmaceuticals are necessary to help bone recovery.

  2. Pitx1 determines characteristic hindlimb morphologies in cartilage micromass culture.

    Directory of Open Access Journals (Sweden)

    Natalie C Butterfield

    Full Text Available The shapes of homologous skeletal elements in the vertebrate forelimb and hindlimb are distinct, with each element exquisitely adapted to their divergent functions. Many of the signals and signalling pathways responsible for patterning the developing limb bud are common to both forelimb and hindlimb. How disparate morphologies are generated from common signalling inputs during limb development remains poorly understood. We show that, similar to what has been shown in the chick, characteristic differences in mouse forelimb and hindlimb cartilage morphology are maintained when chondrogenesis proceeds in vitro away from the endogenous limb bud environment. Chondrogenic nodules that form in high-density micromass cultures derived from forelimb and hindlimb buds are consistently different in size and shape. We described analytical tools we have developed to quantify these differences in nodule morphology and demonstrate that characteristic hindlimb nodule morphology is lost in the absence of the hindlimb-restricted limb modifier gene Pitx1. Furthermore, we show that ectopic expression of Pitx1 in the forelimb is sufficient to generate nodule patterns characteristic of the hindlimb. We also demonstrate that hindlimb cells are less adhesive to the tissue culture substrate and, within the limb environment, to the extracellular matrix and to each other. These results reveal autonomously programmed differences in forelimb and hindlimb cartilage precursors of the limb skeleton are controlled, at least in part, by Pitx1 and suggest this has an important role in generating distinct limb-type morphologies. Our results demonstrate that the micromass culture system is ideally suited to study cues governing morphogenesis of limb skeletal elements in a simple and experimentally tractable in vitro system that reflects in vivo potential.

  3. Pitx1 determines characteristic hindlimb morphologies in cartilage micromass culture. (United States)

    Butterfield, Natalie C; Qian, Chen; Logan, Malcolm P O


    The shapes of homologous skeletal elements in the vertebrate forelimb and hindlimb are distinct, with each element exquisitely adapted to their divergent functions. Many of the signals and signalling pathways responsible for patterning the developing limb bud are common to both forelimb and hindlimb. How disparate morphologies are generated from common signalling inputs during limb development remains poorly understood. We show that, similar to what has been shown in the chick, characteristic differences in mouse forelimb and hindlimb cartilage morphology are maintained when chondrogenesis proceeds in vitro away from the endogenous limb bud environment. Chondrogenic nodules that form in high-density micromass cultures derived from forelimb and hindlimb buds are consistently different in size and shape. We described analytical tools we have developed to quantify these differences in nodule morphology and demonstrate that characteristic hindlimb nodule morphology is lost in the absence of the hindlimb-restricted limb modifier gene Pitx1. Furthermore, we show that ectopic expression of Pitx1 in the forelimb is sufficient to generate nodule patterns characteristic of the hindlimb. We also demonstrate that hindlimb cells are less adhesive to the tissue culture substrate and, within the limb environment, to the extracellular matrix and to each other. These results reveal autonomously programmed differences in forelimb and hindlimb cartilage precursors of the limb skeleton are controlled, at least in part, by Pitx1 and suggest this has an important role in generating distinct limb-type morphologies. Our results demonstrate that the micromass culture system is ideally suited to study cues governing morphogenesis of limb skeletal elements in a simple and experimentally tractable in vitro system that reflects in vivo potential.

  4. Dense distributed processing in a hindlimb scratch motor network

    DEFF Research Database (Denmark)

    Guzulaitis, Robertas; Hounsgaard, Jørn Dybkjær


    In reduced preparations, hindlimb movements can be generated by a minimal network of neurons in the limb innervating spinal segments. The network of neurons that generates real movements is less well delineated. In an ex vivo carapace-spinal cord preparation from adult turtles (Trachemys scripta...... elegans), we show that ventral horn interneurons in mid-thoracic spinal segments are functionally integrated in the hindlimb scratch network. First, mid-thoracic interneurons receive intense synaptic input during scratching and behave like neurons in the hindlimb enlargement. Second, some mid...... of a distributed motor network that secures motor coherence....

  5. Time course changes in [Ca2+]i, force, and protein content in hindlimb-suspended mouse soleus muscles (United States)

    Ingalls, C. P.; Wenke, J. C.; Armstrong, R. B.; Hamilton, S. L. (Principal Investigator)


    BACKGROUND: Exposure to reduced gravitational forces during spaceflight is associated with significant reductions in skeletal muscle mass and strength. The purpose of this study was to test the hypothesis that increases in resting cytosolic free calcium concentration ([Ca2+]i) would precede reductions in protein content and maximal isometric tetanic force (Po) in mouse soleus muscle after initiation of hindlimb suspension. METHODS: Female ICR mice (n = 42) were hindlimb suspended for 1, 2, 3, 5, or 7 d; weight-matched mice were used as controls. Following the hindlimb suspension, the left soleus muscle was used to determine Po in vitro and the right soleus muscle was used to determine protein content and [Ca2+]i via confocal laser scanning microscopy. RESULTS: Compared with controls, [Ca2+]i was elevated by 38% at 2 d, and 117% at 7 d. Compared with controls, soleus muscle total and myofibrillar protein contents were reduced 27-29% and 30-34%, respectively, at 5-7 d after initiation of hindlimb suspension. Compared with controls, soleus muscle Po was decreased by 24% at 3 d, and 38% at 7 d. CONCLUSION: It appears that resting cytosolic Ca2+ homeostasis is disturbed soon after the initiation of hindlimb suspension, and these elevations in [Ca2+]i may play a role in initiating soleus muscle atrophy.

  6. MAFbx/Atrogin-1 is required for atrophic remodeling of the unloaded heart (United States)

    Baskin, Kedryn K.; Rodriguez, Meredith R.; Kansara, Seema; Chen, Wenhao; Carranza, Sylvia; Frazier, O. Howard; Glass, David J.; Taegtmeyer, Heinrich


    Background Mechanical unloading of the failing human heart induces profound cardiac changes resulting in the reversal of a distorted structure and function. In this process, cardiomyocytes break down unneeded proteins and replace those with new ones. The specificity of protein degradation via the ubiquitin proteasome system is regulated by ubiquitin ligases. Over-expressing the ubiquitin ligase MAFbx/Atrogin-1 in the heart inhibits the development of cardiac hypertrophy, but the role of MAFbx/Atrogin-1 in the unloaded heart is not known. Methods and Results Mechanical unloading, by heterotopic transplantation, decreased heart weight and cardiomyocyte cross-sectional area in wild type mouse hearts. Unexpectedly, MAFbx/Atrogin-1−/− hearts hypertrophied after transplantation (n=8–10). Proteasome activity and markers of autophagy were increased to the same extent in WT and MAFbx/Atrogin-1−/− hearts after transplantation (unloading). Calcineurin, a regulator of cardiac hypertrophy, was only upregulated in MAFbx/Atrogin-1−/− transplanted hearts, while the mTOR pathway was similarly activated in unloaded WT and MAFbx/Atrogin-1−/− hearts. MAFbx/Atrogin-1−/− cardiomyocytes exhibited increased calcineurin protein expression, NFAT transcriptional activity, and protein synthesis rates, while inhibition of calcineurin normalized NFAT activity and protein synthesis. Lastly, mechanical unloading of failing human hearts with a left ventricular assist device (n=18) also increased MAFbx/Atrogin-1 protein levels and expression of NFAT regulated genes. Conclusions MAFbx/Atrogin-1 is required for atrophic remodeling of the heart. During unloading, MAFbx/Atrogin-1 represses calcineurin-induced cardiac hypertrophy. Therefore, MAFbx/Atrogin-1 not only regulates protein degradation, but also reduces protein synthesis, exerting a dual role in regulating cardiac mass. PMID:24650875

  7. Body weight unloading modifications on frontal plane joint moments, impulses and Center of Pressure during overground gait. (United States)

    Fischer, Arielle G; Wolf, Alon


    Body weight unloading is a common method of gait rehabilitation. However, little is known about its effects on the overground gait biomechanical parameters which were often confounded by the walking modality (treadmill) or the speed variability when subjects walked overground while having to pull the body weight unloading system to which they were attached. By designing a mechanical device that pulled the system at a constant speed, we were able to assess the unique effects of body weight unloading on healthy subjects' kinetics during overground gait. Fifteen healthy subjects walked overground under three (0%, 15%, and 30%) body weight unloading experimental conditions. Kinetic measures included hip and knee frontal plane moments and impulses and the foot center of pressure. A significant inverse relationship was shown between increased body weight unloading levels (0% to 30%) and a decrease in the hip and knee first adduction moments and impulses and an increase in the lateral shift of the foot center of pressure. Frontal plane hip and knee kinetic curvature patterns remained similar as evidenced by low normalized RMSE under paired comparisons of the experimental conditions. Overground gait with up to 30% body weight unloading stands out as an efficient method of reducing loads on joints without distorting kinetic gait curvature patterns. The relationship between increased unloading with decreased hip and knee moments and impulses and increased lateral shift of the center of pressure also suggests that this shift may be an important diagnostic tool in gait assessment and correction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Nutrition and resistance exercise during reconditioning from unloading. (United States)

    Hackney, Kyle J; Cook, Summer B; Ploutz-Snyder, Lori L


    The recovery of muscle size and function following musculoskeletal unloading has received little attention in the scientific literature. Nutritional factors such as total energy, protein intake, and the pre- and/or post-exercise consumption of amino acid-carbohydrate (AACHO) have been shown to be important for enhancing training adaptations in recreational exercisers. A preliminary study was conducted to explore the interaction between nutrition and resistance exercise during reconditioning from unloading. Muscle CSA, strength, and endurance were measured during a control period following 30 d of unilateral lower limb suspension (Post-ULLS) and after 18 d of reconditioning (ReCon). Six participants consumed either AACHO (979 kJ, 36 g carbohydrate, 22.5 g protein) or placebo (PLAC) prior to resistance exercise (3 d x wk(-1)) during reconditioning. Total daily energy and macronutrient intake were evaluated from dietary journals. From Post-ULLS to ReCon, muscle endurance increased 1.1 +/- 0.6 min in AACHO and decreased 1.3 +/- 0.7 min in PLAC. Muscle CSA (6 +/- 2 vs. 5 +/- 3 cm2) and strength (105 +/- 53 vs. 81 +/- 37 N) increased similarly in AACHO and PLAC, respectively. When groups were pooled there was a significant correlation between daily protein intake and the recovery of muscle CSA (r = 0.81). Although our findings are preliminary, timing AACHO intake during reconditioning was beneficial for muscular endurance, while overall protein intake was associated with increased muscle size. A systematic evaluation into the synergistic relationship between nutrition and exercise during muscular recovery from prolonged unloading is warranted.

  9. Apparatus and method for magnetically unloading a rotor bearing

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, Seth Robert


    An apparatus and method for unloading a rotor bearing is described. The apparatus includes an electromagnet for levitating the rotor. In one embodiment, a sensor of the magnetic field near the electromagnet is used to control the current to levitate the rotor. In another embodiment, a method is provided that includes rotating the rotor, increasing the current to levitate the rotor and decrease the gap between electromagnet and rotor, and then reducing the current to levitate the rotor with a minimal amount of electric power to the electromagnet.

  10. Spinal Health during Unloading and Reloading Associated with Spaceflight

    Directory of Open Access Journals (Sweden)

    David A. Green


    Full Text Available Spinal elongation and back pain are recognized effects of exposure to microgravity, however, spinal health has received relatively little attention. This changed with the report of an increased risk of post-flight intervertebral disc (IVD herniation and subsequent identification of spinal pathophysiology in some astronauts post-flight. Ground-based analogs, particularly bed rest, suggest that a loss of spinal curvature and IVD swelling may be factors contributing to unloading-induced spinal elongation. In flight, trunk muscle atrophy, in particular multifidus, may precipitate lumbar curvature loss and reduced spinal stability, but in-flight (ultrasound and pre- and post-flight (MRI imaging have yet to detect significant IVD changes. Current International Space Station missions involve short periods of moderate-to-high spinal (axial loading during running and resistance exercise, superimposed upon a background of prolonged unloading (microgravity. Axial loading acting on a dysfunctional spine, weakened by anatomical changes and local muscle atrophy, might increase the risk of damage/injury. Alternatively, regular loading may be beneficial. Spinal pathology has been identified in-flight, but there are few contemporary reports of in-flight back injury and no recent studies of post-flight back injury incidence. Accurate routine in-flight stature measurements, in- and post-flight imaging, and tracking of pain and injury (herniation for at least 2 years post-flight is thus warranted. These should be complemented by ground-based studies, in particular hyper buoyancy floatation (HBF a novel analog of spinal unloading, in order to elucidate the mechanisms and risk of spinal injury, and to evaluate countermeasures for exploration where injury could be mission critical.

  11. Growth hormone/IGF-I and/or resistive exercise maintains myonuclear number in hindlimb unweighted muscles (United States)

    Allen, D. L.; Linderman, J. K.; Roy, R. R.; Grindeland, R. E.; Mukku, V.; Edgerton, V. R.


    In the present study of rats, we examined the role, during 2 wk of hindlimb suspension, of growth hormone/insulin-like growth factor I (GH/IGF-I) administration and/or brief bouts of resistance exercise in ameliorating the loss of myonuclei in fibers of the soleus muscle that express type I myosin heavy chain. Hindlimb suspension resulted in a significant decrease in mean soleus wet weight that was attenuated either by exercise alone or by exercise plus GH/IGF-I treatment but was not attenuated by hormonal treatment alone. Both mean myonuclear number and mean fiber cross-sectional area (CSA) of fibers expressing type I myosin heavy chain decreased after 2 wk of suspension compared with control (134 vs. 162 myonuclei/mm and 917 vs. 2,076 micron2, respectively). Neither GH/IGF-I treatment nor exercise alone affected myonuclear number or fiber CSA, but the combination of exercise and growth-factor treatment attenuated the decrease in both variables. A significant correlation was found between mean myonuclear number and mean CSA across all groups. Thus GH/IGF-I administration and brief bouts of muscle loading had an interactive effect in attenuating the loss of myonuclei induced by chronic unloading.

  12. Musculoskeletal Geometry, Muscle Architecture and Functional Specialisations of the Mouse Hindlimb (Open Access) (United States)


    internal structure of these hindlimb muscles, as well as their functional roles in movement, will support both basic science and medicine . Previ- ous... Veterinary College, 4 Royal College Street, London, NW1 0TU, United Kingdom, 2 Structure and Motion Lab, Comparative Biomedical Sciences, Royal Veterinary ...fibres and its internal tendon or main line of action. A pennate fibre arrangement increases the number of muscle fibres which attach to this internal

  13. Patterns of global gene expression in rat skeletal muscle during unloading and low-intensity ambulatory activity (United States)

    Bey, Lionel; Akunuri, Nagabhavani; Zhao, Po; Hoffman, Eric P.; Hamilton, Deborah G.; Hamilton, Marc T.


    Physical inactivity and unloading lead to diverse skeletal muscle alterations. Our goal was to identify the genes in skeletal muscle whose expression is most sensitive to periods of unloading/reduced physical activity and that may be involved in triggering initial responses before phenotypic changes are evident. The ability of short periods of physical activity/loading as an effective countermeasure against changes in gene expression mediated by inactivity was also tested. Affymetrix microarrays were used to compare mRNA levels in the soleus muscle under three experimental treatments (n = 20-29 rats each): 12-h hindlimb unloading (HU), 12-h HU followed by 4 h of intermittent low-intensity ambulatory and postural activity (4-h reloading), and control (with ambulatory and postural activity). Using a combination of criteria, we identified a small set of genes (approximately 1% of 8,738 genes on the array or 4% of significant expressed genes) with the most reproducible and largest responses to altered activity. Analysis revealed a coordinated regulation of transcription for a large number of key signaling proteins and transcription factors involved in protein synthesis/degradation and energy metabolism. Most (21 of 25) of the gene expression changes that were downregulated during HU returned at least to control levels during the reloading. In surprising contrast, 27 of 38 of the genes upregulated during HU remained significantly above control, but most showed trends toward reversal. This introduces a new concept that, in general, genes that are upregulated during unloading/inactivity will be more resistant to periodic reloading than those genes that are downregulated. This study reveals genes that are the most sensitive to loading/activity in rat skeletal muscle and indicates new targets that may initiate muscle alterations during inactivity.

  14. Patterns of fusimotor activity during locomotion in the decerebrate cat deduced from recordings from hindlimb muscle spindles (United States)

    Taylor, A; Durbaba, R; Ellaway, P H; Rawlinson, S


    Recordings have been made from multiple single muscle spindle afferents from medial gastrocnemius (MG) and tibialis anterior (TA) muscles of one hindlimb in decerebrate cats, together with ankle rotation and EMG signals, during treadmill locomotion. Whilst the other three limbs walked freely, the experimental limb was denervated except for the nerves to MG and TA and secured so that it could rotate only at the ankle joint, without any external load. Each afferent was characterised by succinylcholine testing with regard to its intrafusal fibre contacts. Active movements were recorded and then replayed through a servo mechanism to reproduce the muscle length changes passively after using a barbiturate to suppress γ-motor firing. The difference in secondary afferent firing obtained by subtracting the discharge during passive movements from that during active movements was taken to represent the profile of static fusimotor activity. This indicated an increase before the onset of movement followed by a strongly modulated discharge in parallel with muscle shortening during locomotion. The pattern of static firing matched the pattern of unloaded muscle shortening very closely in the case of TA and with some phase advance in the case of MG. The same effects were observed in primary afferents. Primary afferents with bag1 (b1) contacts in addition showed higher firing frequencies during muscle lengthening in active than in passive movements. This indicated increased dynamic fusimotor firing during active locomotion. There was no evidence as to whether this fluctuated during the movement cycles. When the mean active minus passive difference profile of firing in bag2-chain (b2c) type primary afferents was subtracted from that for b1b2c afferents, the difference was dominated by a peak centred on the moment of maximum lengthening velocity (v). The component of the active minus passive difference firing due to b1 fibre contacts could be modelled by f(t) =av (where a is a

  15. Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats. (United States)

    Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Li, Feijiang; Xu, Qiaoling; Xie, Kangning; Tang, Chi; Liu, Juan; Guo, Wei; Wu, Xiaoming; Jiang, Maogang; Luo, Erping


    A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, β-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities

  16. Forelimb-hindlimb developmental timing changes across tetrapod phylogeny

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    Selwood Lynne


    Full Text Available Abstract Background Tetrapods exhibit great diversity in limb structures among species and also between forelimbs and hindlimbs within species, diversity which frequently correlates with locomotor modes and life history. We aim to examine the potential relation of changes in developmental timing (heterochrony to the origin of limb morphological diversity in an explicit comparative and quantitative framework. In particular, we studied the relative time sequence of development of the forelimbs versus the hindlimbs in 138 embryos of 14 tetrapod species spanning a diverse taxonomic, ecomorphological and life-history breadth. Whole-mounts and histological sections were used to code the appearance of 10 developmental events comprising landmarks of development from the early bud stage to late chondrogenesis in the forelimb and the corresponding serial homologues in the hindlimb. Results An overall pattern of change across tetrapods can be discerned and appears to be relatively clade-specific. In the primitive condition, as seen in Chondrichthyes and Osteichthyes, the forelimb/pectoral fin develops earlier than the hindlimb/pelvic fin. This pattern is either retained or re-evolved in eulipotyphlan insectivores (= shrews, moles, hedgehogs, and solenodons and taken to its extreme in marsupials. Although exceptions are known, the two anurans we examined reversed the pattern and displayed a significant advance in hindlimb development. All other species examined, including a bat with its greatly enlarged forelimbs modified as wings in the adult, showed near synchrony in the development of the fore and hindlimbs. Conclusion Major heterochronic changes in early limb development and chondrogenesis were absent within major clades except Lissamphibia, and their presence across vertebrate phylogeny are not easily correlated with adaptive phenomena related to morphological differences in the adult fore- and hindlimbs. The apparently conservative nature of this

  17. Forelimb-hindlimb developmental timing changes across tetrapod phylogeny. (United States)

    Bininda-Emonds, Olaf R P; Jeffery, Jonathan E; Sánchez-Villagra, Marcelo R; Hanken, James; Colbert, Matthew; Pieau, Claude; Selwood, Lynne; Ten Cate, Carel; Raynaud, Albert; Osabutey, Casmile K; Richardson, Michael K


    Tetrapods exhibit great diversity in limb structures among species and also between forelimbs and hindlimbs within species, diversity which frequently correlates with locomotor modes and life history. We aim to examine the potential relation of changes in developmental timing (heterochrony) to the origin of limb morphological diversity in an explicit comparative and quantitative framework. In particular, we studied the relative time sequence of development of the forelimbs versus the hindlimbs in 138 embryos of 14 tetrapod species spanning a diverse taxonomic, ecomorphological and life-history breadth. Whole-mounts and histological sections were used to code the appearance of 10 developmental events comprising landmarks of development from the early bud stage to late chondrogenesis in the forelimb and the corresponding serial homologues in the hindlimb. An overall pattern of change across tetrapods can be discerned and appears to be relatively clade-specific. In the primitive condition, as seen in Chondrichthyes and Osteichthyes, the forelimb/pectoral fin develops earlier than the hindlimb/pelvic fin. This pattern is either retained or re-evolved in eulipotyphlan insectivores (= shrews, moles, hedgehogs, and solenodons) and taken to its extreme in marsupials. Although exceptions are known, the two anurans we examined reversed the pattern and displayed a significant advance in hindlimb development. All other species examined, including a bat with its greatly enlarged forelimbs modified as wings in the adult, showed near synchrony in the development of the fore and hindlimbs. Major heterochronic changes in early limb development and chondrogenesis were absent within major clades except Lissamphibia, and their presence across vertebrate phylogeny are not easily correlated with adaptive phenomena related to morphological differences in the adult fore- and hindlimbs. The apparently conservative nature of this trait means that changes in chondrogenetic patterns may serve

  18. Does the beta2-agonist clenbuterol help to maintain myocardial potential to recover during mechanical unloading? (United States)

    Tsuneyoshi, Hiroshi; Oriyanhan, Wnimunk; Kanemitsu, Hideo; Shiina, Reiko; Nishina, Takeshi; Matsuoka, Satoshi; Ikeda, Tadashi; Komeda, Masashi


    Chronic mechanical unloading induces left ventricular (LV) atrophy, which may impair functional recovery during support with an LV-assist device. Clenbuterol, a beta2-adrenergic receptor (AR) agonist, is known to induce myocardial hypertrophy and might prevent LV atrophy during LV unloading. Furthermore, beta2-AR stimulation is reported to improve Ca2+ handling and contribute to antiapoptosis. However, there is little information on the effects of clenbuterol during LV unloading. We investigated LV atrophy and function after LV unloading produced by heterotopic heart transplantation in isogenic rats. After transplantation, rats were randomized to 1 of 2 groups (n=10 each). The clenbuterol group received 2 of the drug for 2 weeks; the control group received normal saline. The weight of unloaded control hearts was 48% less than that of host hearts after 2 weeks of unloading. Clenbuterol significantly increased the weight of the host hearts but did not prevent unloading-induced LV atrophy. Papillary muscles were isolated and stimulated, and there was no difference in developed tension between the 2 groups. However, the inotropic response to the beta-AR agonist isoproterenol significantly improved in the clenbuterol group. The mRNA expression of myocardial sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) and fetal gene shift (myosin heavy chain [MHC] mRNA isozyme) was also significantly improved by clenbuterol treatment. There was no difference in beta1-AR mRNA expression between the 2 groups. In contrast, beta2-AR mRNA was significantly decreased in the clenbuterol-treated, unloaded heart. This indicates that clenbuterol may downregulate beta2-ARs. In the evaluation of apoptosis, mRNA expression of caspase-3, which is the central pathway for apoptosis, tended to be better in the clenbuterol group. During complete LV unloading, clenbuterol did not prevent myocardial atrophy but improved gene expression (SERCA2a, beta-MHC) and beta

  19. Moderate-intensity rotating magnetic fields do not affect bone quality and bone remodeling in hindlimb suspended rats.

    Directory of Open Access Journals (Sweden)

    Da Jing

    Full Text Available Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF and static magnetic fields (SMF on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF, another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10, HU (n = 10 and HU with RMF exposure (HU+RMF, n = 12 groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates

  20. Moderate-intensity rotating magnetic fields do not affect bone quality and bone remodeling in hindlimb suspended rats. (United States)

    Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Zhai, Mingming; Tong, Shichao; Xu, Qiaoling; Xie, Kangning; Wu, Xiaoming; Tang, Chi; Xu, Xinmin; Liu, Juan; Guo, Wei; Jiang, Maogang; Luo, Erping


    Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF), another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates potentially

  1. Rat hindlimb joint immobilization with acrylic resin orthoses

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    C.A. da Silva


    Full Text Available The objective of the present study was to propose an orthosis of light material that would be functional for the animal and that would maintain only the ankle joint immobilized. Male Wistar rats (3 to 4 months old, 250-300 g were divided into 2 groups (N = 6: control and immobilized for 7 days. Rats were anesthetized with sodium pentobarbital (40 mg/kg weight and the left hindlimb was immobilized with the orthoses composed of acrylic resin model, abdominal belt and lateral supports. The following analyses were performed: glycogen content of the soleus, extensor digitorum longus, white gastrocnemius, red gastrocnemius, and tibialis anterior muscles by the phenol sulfuric method, and the weight, fiber area and intramuscular connective tissue of the soleus by the planimetric system. Data were analyzed statistically by the Kolmogorov-Smirnov, Student t and Wilcoxon tests. Immobilization decreased glycogen in all muscles (P < 0.05; soleus: 31.6%, white gastrocnemius: 56.6%, red gastrocnemius: 39%, extensor digitorum longus: 41.7%, tibialis anterior: 45.2% in addition to reducing soleus weight by 34% (P < 0.05. Furthermore, immobilization promoted reduction of the fiber area (43%, P < 0.05 and increased the connective tissue (200%, P < 0.05. The orthosis model was efficient comparing with another alternative immobilization model, like plaster casts, in promoting skeletal muscle alterations, indicating that it could be used as a new model in other studies related to muscle disuse.

  2. The hindlimb muscles of Rhea americana (Aves, Palaeognathae, Rheidae). (United States)

    Picasso, M B J


    The Greater Rhea is the largest cursorial Ratitae bird native to South America. Due to its increasing importance in farming and therefore in the sustainable use of this species, a comprehensive knowledge of their anatomy is essential. The goal of this study was to provide an anatomical description of the hindlimb muscles of Rhea americana. Six adult birds of both sexes were macroscopically studied analysing the origin and insertion of thigh and shank muscles. The thigh showed the highest number of muscles, whereas the shank showed the lowest number; this feature minimizes inertia and allows achieving high stride frequencies. The muscles of the shank showed long tendons of insertion that reduce the energetic cost during running. The major muscles responsible for extension of the hip and the ankle joints were massive and robust indicating their importance for cursorial locomotion. The pelvic limb muscles of Rhea americana resemble those of other cursorial Ratitae and their features are consistent with specialization for high-speed locomotion. © 2010 Blackwell Verlag GmbH.

  3. Cat hindlimb tactile dermatomes determined with single-unit recordings. (United States)

    Brown, P B; Koerber, H R


    1. Single-unit recording from dorsal root ganglia was used to determine the dermatomes of L4-S2 segments in the cat. Dermatomes for low-threshold myelinated mechanoreceptor afferents are smaller than those reported in earlier studies of whole-root dermatomes. There are also sufficient discrepancies among earlier studies and with the present data to merit reexamination of hindlimb whole-root dermatomes. 2. Receptive-field size varies directly with distance from toes. Length/width ratio is essentially constant for different parts of the hindlimb. 3. Estimates of innervation density verify the long-standing assumption that innervation density is greater for foot and toes than for proximal hindlimb, at least for low-threshold cutaneous myelinated afferents.

  4. Enhanced angiogenic effect of adipose-derived stromal cell spheroid with low-level light therapy in hindlimb ischemia mice (United States)

    Park, In-Su; Ahn, Jin-Chul; Chung, Phil-Sang


    Adipose-derived stromal cells (ASCs) are attractive cell source for tissue engineering. However, one obstacle to this approach is that the transplanted ASC population can decline rapidly in the recipient tissue. The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on transplanted human ASCs (hASCs) spheroid in a hindlimb ischemia animal model. LLLT, hASCs spheroid and hASCs spheroid transplantation with LLLT (spheroid + LLLT) were applied to the ischemic hindlimbs in athymic mice. The survival, differentiation and secretion of vascular endothelial growth (VEGF) of spheroid ASCs were evaluated by immunohistochemistry. The spheroid + LLLT group enhanced the tissue regeneration, including angiogenesis, compared with other groups. The spheroid contributed tissue regeneration via differentiation and secretion of growth factors. In the spheroid + LLLT group, the survival of spheroid hASCs was increased by the decreased apoptosis of spheroid hASCs in the ischemic hindlimb. The secretion of growth factors was stimulated in the spheroid + LLLT group compared with the ASCs group and spheroid group. These data suggest that LLLT is an effective biostimulator of spheroid hASCs in tissue regeneration that enhances the survival of ASCs and stimulates the secretion of growth factors in the ischemic hindlimb.

  5. Unloading knee brace is a cost-effective method to bridge and delay surgery in unicompartmental knee arthritis (United States)

    Lee, Paul YF; Winfield, Thomas G; Harris, Shaun RS; Storey, Emerald; Chandratreya, Amit


    Background Unloading knee braces can provide good short-term pain relief for some patients with unicompartmental osteoarthritis (UOA). Their cost is relatively small compared with surgical interventions. However, no previous studies have reported their use over a duration of 5 years or more. Methods Up to 8 years of prospective data were collected from 63 patients who presented with UOA. After conservative management with analgesia and physiotherapy, patients were offered an unloading brace. EQ-5D (EuroQol five dimensions) questionnaires were collected at baseline and after wearing the brace. Cost and quality-adjusted life years (QALYs) were compared with a total knee replacement (TKR) with an 8-month waiting duration and 8 years of results. Results Patients experienced a mean increase in EQ-5D of 0.42 with an average duration of wear of 26.1 months resulting in an increase of 0.44 in QALYs with a mean cost of £625. The adoption of an unloader knee brace was found to be a short-term cost-effective treatment option with an 8-month incremental cost effectiveness ratio of £9599. Compared with no treatment, the unloader knee brace can be considered cost effective at 4 months or more. At 8 years follow-up, the unloader knee brace demonstrated QALYs gain of 0.43 and with an incremental cost-effectiveness ratio of -£6467 compared with TKR. Conclusion Unloading knee braces are cost effective for the management of UOA. These findings strongly support the undertaking of further research into the long-term impact of unloading knee brace. The unloader knee brace has benefits to the National Health Service for capacity, budget, waiting list duration, frequency of surgery and reducing the required severity of surgical intervention. PMID:28879034

  6. Grain Unloading of Arsenic Species in Rice

    Energy Technology Data Exchange (ETDEWEB)

    Carey, Anne-Marie; Scheckel, Kirk G.; Lombi, Enzo; Newville, Matt; Choi, Yongseong; Norton, Gareth J.; Charnock, John M.; Feldmann, Joerg; Price, Adam H.; Meharg, Andrew A. (EPA); (U. South Australia); (Manchester); (Aberdeen); (UC)


    Rice (Oryza sativa) is the staple food for over half the world's population yet may represent a significant dietary source of inorganic arsenic (As), a nonthreshold, class 1 human carcinogen. Rice grain As is dominated by the inorganic species, and the organic species dimethylarsinic acid (DMA). To investigate how As species are unloaded into grain rice, panicles were excised during grain filling and hydroponically pulsed with arsenite, arsenate, glutathione-complexed As, or DMA. Total As concentrations in flag leaf, grain, and husk, were quantified by inductively coupled plasma mass spectroscopy and As speciation in the fresh grain was determined by x-ray absorption near-edge spectroscopy. The roles of phloem and xylem transport were investigated by applying a {+-} stem-girdling treatment to a second set of panicles, limiting phloem transport to the grain in panicles pulsed with arsenite or DMA. The results demonstrate that DMA is translocated to the rice grain with over an order magnitude greater efficiency than inorganic species and is more mobile than arsenite in both the phloem and the xylem. Phloem transport accounted for 90% of arsenite, and 55% of DMA, transport to the grain. Synchrotron x-ray fluorescence mapping and fluorescence microtomography revealed marked differences in the pattern of As unloading into the grain between DMA and arsenite-challenged grain. Arsenite was retained in the ovular vascular trace and DMA dispersed throughout the external grain parts and into the endosperm. This study also demonstrates that DMA speciation is altered in planta, potentially through complexation with thiols.

  7. Slow recovery of the impaired fatigue resistance in postunloading mouse soleus muscle corresponding to decreased mitochondrial function and a compensatory increase in type I slow fibers (United States)

    Feng, Han-Zhong; Chen, Xuequn; Malek, Moh H.


    Unloading or disuse rapidly results in skeletal muscle atrophy, switching to fast-type fibers, and decreased resistance to fatigue. The recovery process is of major importance in rehabilitation for various clinical conditions. Here we studied mouse soleus muscle during 60 days of reloading after 4 wk of hindlimb suspension. Unloading produced significant atrophy of soleus muscle with decreased contractile force and fatigue resistance, accompanied by switches of myosin isoforms from IIa to IIx and IIb and fast troponin T to more low-molecular-weight splice forms. The total mass, fiber size, and contractile force of soleus muscle recovered to control levels after 15 days of reloading. However, the fatigue resistance showed a trend of worsening during this period with significant infiltration of inflammatory cells at days 3 and 7, indicating reloading injuries that were accompanied by active regeneration with upregulations of filamin-C, αB-crystallin, and desmin. The fatigue resistance partially recovered after 30–60 days of reloading. The expression of peroxisome proliferator-activated receptor γ coactivator 1α and mitofusin-2 showed changes parallel to that of fatigue resistance after unloading and during reloading, suggesting a causal role of decreased mitochondrial function. Slow fiber contents in the soleus muscle were increased after 30–60 days of reloading to become significantly higher than the normal level, indicating a secondary adaption to compensate for the slow recovery of fatigue resistance. PMID:26447205

  8. Possible mechanism for changes in glycogen metabolism in unloaded soleus muscle (United States)

    Henriksen, E. J.; Tischler, M. E.


    Carbohydrate metabolism has been shown to be affected in a number of ways by different models of hypokinesia. In vivo glycogen levels in the soleus muscle are known to be increased by short-term denervation and harness suspension. In addition, exposure to 7 days of hypogravity also caused a dramatic increase in glycogen concentration in this muscle. The biochemical alterations caused by unloading that may bring about these increases in glycogen storage in the soleus were sought.

  9. Biomechanics and structural adaptations of the rat femur after hindlimb suspension and treadmill running

    Directory of Open Access Journals (Sweden)

    M.M. Shimano


    Full Text Available We microscopically and mechanically evaluated the femurs of rats subjected to hindlimb unloading (tail suspension followed by treadmill training. Female Wistar rats were randomly divided into five groups containing 12-14 rats: control I (118 days old, control II (139 days old, suspended (tail suspension for 28 days, suspended-released (released for 21 days after 28 days of suspension, and suspended-trained (trained for 21 days after 28 days of suspension. We measured bone resistance by bending-compression mechanical tests of the entire proximal half of the femur and three-point bending tests of diaphyseal cortical bone. We determined bone microstructure by tetracycline labeling of trabecular and cortical bone. We found that tail suspension weakened bone (ultimate load = 86.3 ± 13.5 N, tenacity modulus = 0.027 ± 0.011 MPa·m vs ultimate load = 101.5 ± 10.5 N, tenacity modulus = 0.019 ± 0.006 MPa·m in control I animals. The tenacity modulus for suspended and released animals was 0.023 ± 0.010 MPa·m vs 0.046 ± 0.018 MPa·m for trained animals and 0.035 ± 0.010 MPa·m for control animals. These data indicate that normal activity and training resulted in recovered bone resistance, but suspended-released rats presented femoral head flattening and earlier closure of the growth plate. Microscopically, we found that suspension inhibited new bone subperiosteal and endosteal formation. The bone disuse atrophy secondary to hypoactivity in rats can be reversed by an early regime of exercising, which is more advantageous than ordinary cage activities alone.

  10. Modulation of joint moments and work in the goat hindlimb with locomotor speed and surface grade. (United States)

    Arnold, Allison S; Lee, David V; Biewener, Andrew A


    Goats and other quadrupeds must modulate the work output of their muscles to accommodate the changing mechanical demands associated with locomotion in their natural environments. This study examined which hindlimb joint moments goats use to generate and absorb mechanical energy on level and sloped surfaces over a range of locomotor speeds. Ground reaction forces and the three-dimensional locations of joint markers were recorded as goats walked, trotted and galloped over 0, +15 and -15 deg sloped surfaces. Net joint moments, powers and work were estimated at the goats' hip, knee, ankle and metatarsophalangeal joints throughout the stance phase via inverse dynamics calculations. Differences in locomotor speed on the level, inclined and declined surfaces were characterized and accounted for by fitting regression equations to the joint moment, power and work data plotted versus non-dimensionalized speed. During level locomotion, the net work generated by moments at each of the hindlimb joints was small (less than 0.1 J kg(-1) body mass) and did not vary substantially with gait or locomotor speed. During uphill running, by contrast, mechanical energy was generated at the hip, knee and ankle, and the net work at each of these joints increased dramatically with speed (Pgoats generated larger knee extension moments in the first half of stance, absorbing energy as the knee flexed, and goats generated smaller ankle extension moments in the second half of stance, delivering less energy. The goats' hip extension moment in mid-stance was also diminished, contributing to the decrease in energy. These analyses offer new insight into quadrupedal locomotion, clarifying how the moments generated by hindlimb muscles modulate mechanical energy at different locomotor speeds and grades, as needed to accommodate the demands of variable terrain.

  11. The Hindlimb Myology of Tyto alba (Tytonidae, Strigiformes, Aves). (United States)

    Mosto, M C


    This work is the first myological dissection performed in detail on the hindlimb of Tyto alba. Six specimens were dissected and their muscle masses were obtained. T. alba has the classical myological pattern present in other species of Strigiformes, such as a well-developed m. flexor digitorum longus and the absence of the m. plantaris, flexor cruris lateralis and ambiens. Also, T. alba lacks the m. extensor propius digiti III, m. extensor propius digiti IV and m. lumbricalis, present in the Strigidae. Hindlimb muscle mass accounts for 14.13% of total body mass, which is within the range of values of both nocturnal (Strigiformes) and diurnal (Falconidae and Accipitridae) raptors. This study provides important information for future studies related to functional morphology and ecomorphology. © 2016 Blackwell Verlag GmbH.

  12. Research on automatic loading & unloading technology for vertical hot ring rolling process


    Xiaokai Wang; Dehui Wang; Xuesong Mei; Lin Hua; Yutong Dai; Jian Wu


    The automatic loading & unloading technology is the key to the automatic ring production line. In this paper, the automatic vertical hot ring rolling (VHRR) process is taken as the target, the method of the loading & unloading for VHRR is proposed, and the mechanical structure of loading & unloading system is designed, The virtual prototype model of VHRR mill and loading & unloading mechanism is established, and the coordinated control method of VHRR mill and loading & unloading auxiliaries i...

  13. Head pitch affects muscle activity in the decerebrate cat hindlimb during walking. (United States)

    Gottschall, Jinger S; Nichols, T Richard


    Our purpose was to quantify the effects of head pitch on muscle activity patterns of the decerebrate cat hindlimb during walking. Five decerebrate cats walked at 0.7 m/s on a treadmill positioned level with the head pitch either parallel to the treadmill, 50% nose down or 50% nose up. We collected electromyography data from six hindlimb muscles. During level walking, after we manipulated head pitch, our results were surprisingly equivalent to the research on slope walking. For instance, muscle activity during level walking with a 50% head pitch nose down mimicked uphill walking. The muscle activity of the iliopsoas and semitendinosus significantly increased. Muscle activity during level walking with a 50% head pitch nose up mimicked downhill walking. Specifically, the biceps femoris and semimembranosus were inactive during the entire step. These alterations in muscle activity occurred within one step of altering head pitch but dissipated as level walking continued. In conclusion, the time course of muscle activity patterns due to modifications in head pitch is immediate and transitory.

  14. The diaphragm is better protected from oxidative stress than hindlimb skeletal muscle during CLP-induced sepsis. (United States)

    Talarmin, Hélène; Derbré, Frédéric; Lefeuvre-Orfila, Luz; Léon, Karelle; Droguet, Mickaël; Pennec, Jean-Pierre; Giroux-Metgès, Marie-Agnès


    The aim of this study was to determine whether non-lethal sepsis induced by cecal ligation and puncture (CLP) modulates oxidative damage and enzymatic antioxidant defenses in diaphragm and hindlimb skeletal muscles (soleus and Extensor Digitorus Longus (EDL)). Female Wistar rats were divided into four experimental groups: (1) control animals, (2) animals sacrificed 2 hours or (3) 7 days after CLP, and (4) sham-operated animals. At the end of the experimental procedure, EDL, soleus, and diaphragm muscles were harvested and 4-hydroxynonenal (HNE)-protein adducts and protein carbonyl contents were examined in relation to superoxide dismutase and catalase expression and activities. We observed that both non-respiratory oxidative (i.e. soleus) and glycolytic skeletal muscles (i.e. EDL) are more susceptible to sepsis-induced oxidative stress than diaphragm, as attested by an increase in 4-HNE protein adducts and carbonylated proteins after 2 hours of CLP only in soleus and EDL. These differences could be explained by higher basal enzymatic antioxidant activities in diaphragm compared to hindlimb skeletal muscles. Together, these results demonstrate that diaphragm is better protected from oxidative stress than hindlimb skeletal muscles during CLP-induced sepsis.

  15. Accuracy of unloading with the anti-gravity treadmill. (United States)

    McNeill, David K P; de Heer, Hendrik D; Bounds, Roger G; Coast, J Richard


    Body weight (BW)-supported treadmill training has become increasingly popular in professional sports and rehabilitation. To date, little is known about the accuracy of the lower-body positive pressure treadmill. This study evaluated the accuracy of the BW support reported on the AlterG "Anti-Gravity" Treadmill across the spectrum of unloading, from full BW (100%) to 20% BW. Thirty-one adults (15 men and 16 women) with a mean age of 29.3 years (SD = 10.9), and a mean weight of 66.55 kg (SD = 12.68) were recruited. Participants were weighed outside the machine and then inside at 100-20% BW in 10% increments. Predicted BW, as presented by the AlterG equipment, was compared with measured BW. Significant differences between predicted and measured BW were found at all but 90% through 70% of BW. Differences were small (Anti-Gravity Treadmill®, with the largest differences (>5%) found at 100% BW and the greatest BW support (30 and 20% BW). These differences may be associated with changes in metabolic demand and maximum speed during walking or running and should be taken into consideration when using these devices for training and research purposes.

  16. Loading and Unloading Weaned Pigs: Effects of Bedding Types, Ramp Angle, and Bedding Moisture

    Directory of Open Access Journals (Sweden)

    Arlene Garcia


    Full Text Available The use of non-slip surfaces during loading and unloading of weaned pigs plays an important role in animal welfare and economics of the pork industry. Currently, the guidelines available only suggest the use of ramps below 20° to load and unload pigs. Three ramp angles (0°, 10° or 20°, five bedding materials (nothing, sand, feed, wood shavings or wheat straw hay, two moistures (dry or wet bedding; >50% moisture over two seasons (>23.9 °C summer, <23.9 °C winter were assessed for slips/falls/vocalizations (n = 6,000 pig observations. “Score” was calculated by the sum of slips, falls, and vocalizations. With the exception of using feed as a bedding, all beddings provided some protection against elevated slips, falls, and vocalizations (P < 0.01. Providing bedding reduced (P < 0.05 scores regardless of whether the bedding was dry or wet. Scores increased as the slope increased (P < 0.01. Provision of bedding, other than feed, at slopes greater than zero, decreased slips, falls and vocalizations. The total time it took to load and unload pigs was

  17. Encoding of temporal intervals in the rat hindlimb sensorimotor cortex

    Directory of Open Access Journals (Sweden)

    Eric Bean Knudsen


    Full Text Available The gradual buildup of neural activity over experimentally imposed delay periods, termed climbing activity, is well documented and is a potential mechanism by which interval time is encoded by distributed cortico-thalamico-striatal networks in the brain. Additionally, when multiple delay periods are incorporated, this activity has been shown to scale its rate of climbing proportional to the delay period. However, it remains unclear whether these patterns of activity occur within areas of motor cortex dedicated to hindlimb movement. Moreover, the effects of behavioral training (e.g. motor tasks under different reward conditions but with similar behavioral output are not well addressed. To address this, we recorded activity from the hindlimb sensorimotor cortex (HLSMC of two groups of rats performing a skilled hindlimb press task. In one group, rats were trained only to a make a valid press within a finite window after cue presentation for reward (non-interval trained, nIT; n=5, while rats in the second group were given duration-specific cues in which they had to make presses of either short or long duration to receive reward (interval trained, IT; n=6. Using PETH analyses, we show that cells recorded from both groups showed climbing activity during the task in similar proportions (35% IT and 47% nIT, however only climbing activity from IT rats was temporally scaled to press duration. Furthermore, using single trial decoding techniques (Wiener filter, we show that press duration can be inferred using climbing activity from IT animals (R=0.61 significantly better than nIT animals (R=0.507, p<0.01, suggesting IT animals encode press duration through temporally scaled climbing activity. Thus, if temporal intervals are behaviorally relevant then the activity of climbing neurons is temporally scaled to encode the passage of time.

  18. Sucrose Transporter Localization and Function in Phloem Unloading in Developing Stems. (United States)

    Milne, Ricky J; Perroux, Jai M; Rae, Anne L; Reinders, Anke; Ward, John M; Offler, Christina E; Patrick, John W; Grof, Christopher P L


    How sucrose transporters (SUTs) regulate phloem unloading in monocot stems is poorly understood and particularly so for species storing high Suc concentrations. To this end, Sorghum bicolor SUTs SbSUT1 and SbSUT5 were characterized by determining their transport properties heterologously expressed in yeast or Xenopus laevis oocytes, and their in planta cellular and subcellular localization. The plasma membrane-localized SbSUT1 and SbSUT5 exhibited a strong selectivity for Suc and high Suc affinities in X. laevis oocytes at pH 5-SbSUT1, 6.3 ± 0.7 mm, and SbSUT5, 2.4 ± 0.5 mm Suc. The Suc affinity of SbSUT1 was dependent on membrane potential and pH. In contrast, SbSUT5 Suc affinity was independent of membrane potential and pH but supported high transport rates at neutral pH. Suc transport by the tonoplast localized SbSUT4 could not be detected using yeast or X. laevis oocytes. Across internode development, SUTs, other than SbSUT4, were immunolocalized to sieve elements, while for elongating and recently elongated internodes, SUTs also were detected in storage parenchyma cells. We conclude that apoplasmic Suc unloading from de-energized protophloem sieve elements in meristematic zones may be mediated by reversal of SbSUT1 and/or by uniporting SWEETs. Storage parenchyma localized SbSUT1 and SbSUT5 may accumulate Suc from the stem apoplasms of elongating and recently elongated internodes, whereas SbSUT4 may function to release Suc from vacuoles. Transiting from an apoplasmic to symplasmic unloading pathway as the stem matures, SbSUT1 and SbSUT5 increasingly function in Suc retrieval into metaphloem sieve elements to maintain a high turgor to drive symplasmic unloading by bulk flow. © 2017 American Society of Plant Biologists. All Rights Reserved.

  19. The effect of induced hindlimb lameness on thoracolumbar kinematics during treadmill locomotion.

    NARCIS (Netherlands)

    Gomez Alvarez, C.B.; Bobbert, M.F.; Lamers, L.; Johnston, C.; Back, W.; van Weeren, P.R.


    Reasons for performing study: There are no detailed studies describing a relationship between hindlimb lameness and altered motion of the back. Objectives: To quantify the effect of induced subtle hindlimb lameness on thoracolumbar kinematics in the horse. Methods: Kinematics of 6 riding horses were

  20. Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

    NARCIS (Netherlands)

    DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.


    Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral

  1. Hindlimb suspension and SPE-like radiation impairs clearance of bacterial infections.

    Directory of Open Access Journals (Sweden)

    Minghong Li

    Full Text Available A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health.

  2. The hindlimb myology of Milvago chimango (Polyborinae, Falconidae). (United States)

    Mosto, María Clelia; Carril, Julieta; Picasso, Mariana Beatriz Julieta


    We describe the hindlimb myology of Milvago chimango. This member of the Falconidae: Polyborinae is a generalist and opportunist that can jump and run down prey on the ground, unlike Falconinae that hunt birds in flight and kill them by striking with its talons. Due to differences in the locomotion habits between the subfamilies, we hypothesized differences in their hindlimb myology. Gross dissections showed that the myology of M. chimango is concordant with that described of other falconids, except for the following differences: the m. flexor cruris medialis has one belly with a longitudinal division; the m. iliotibialis lateralis does not have a connection with the m. iliofibularis; the m. fibularis longus is strongly aponeurotic; the m. tibialis cranialis lacks an accessory tendons and the m. flexor hallucis longus has one place of origin, instead of two. The presence of the m. flexor cruris lateralis can be distinguished as it has been described absent for the Falconidae. We associated its presence with the predominant terrestrial habit of the M. chimango. Each muscle dissected was weighed and the relationship between flexors and extensors at each joint was assessed. The extensor muscles predominated in all joints in M. chimango. Among the flexors, the m. flexor hallucis longus was the heaviest, which could be related to the importance of the use of its talons to obtain food. Copyright © 2013 Wiley Periodicals, Inc.

  3. Non-skeletal multicentric chondrosarcoma in the hindlimb of a dog. (United States)

    Cohen, Liat; Dank, Gillian; Milgram, Joshua


    An eight-year-old, spayed, female golden retriever was presented with progressive right hindlimb lameness and polyuria/polydipsia. Multiple soft tissue masses were palpable within the hindlimb muscles. A tentative diagnosis of sarcoma was made on fine needle aspiration. A computed tomography scan of the hindlimb and thorax confirmed the presence and location of the masses, none of which were associated with the bones of the hindlimb. In addition, two pulmonary lesions were identified in the right cranial lung lobe. A diagnosis of chondrosarcoma was confirmed on histopathology with a final diagnosis of extraskeletal chondrosarcoma. A high, hindlimb amputation was performed, and chemotherapy was initiated. Polyuria and polydipsia resolved 2 weeks postoperatively. Numerous lung lesions, suspected to be metastases were found on routine followup radiographs, 73 days post surgery after which the dog was lost to follow-up. © 2010 British Small Animal Veterinary Association.

  4. Unloader knee braces for osteoarthritis: do patients actually wear them? (United States)

    Squyer, Emily; Stamper, Daniel L; Hamilton, Deven T; Sabin, Janice A; Leopold, Seth S


    Unloader braces are a nonsurgical approach for predominantly unicompartmental knee arthritis. Although noninvasive, braces are expensive and it is unclear whether clinical factors, if any, will predict regular brace use. We asked: (1) Do patients continue to use the unloader brace more than 1 year after it is prescribed? (2) Do any clinical or radiographic factors predict continued use of the unloader brace after the first year? (3) What are the most common subjective reasons that patients give for discontinuing the brace? We administered 110 surveys to all patients who were fitted for unloader knee braces for predominantly unicompartmental osteoarthritis 12 to 40 months before administration of the survey. Standardized indications and fitting protocols were used. The following parameters were tested for association with ongoing brace use: alignment, arthritis severity, compartment involved, BMI, weight, age, gender, pain and function, number of refittings, and problems with the brace. The survey response rate was 81% (89 of 110). Of the 89 responders, 28% reported regular brace use (twice per week, an hour at a time, or more); at 2 years, 25% used the brace regularly. No clinical or radiographic factors considered were associated with ongoing brace use. Patients reported lack of symptomatic relief, brace discomfort, poor fit, and skin irritation as reasons for discontinuing the brace. Surgeons and patients need to balance the benefits and absence of complications of bracing against cost and the low likelihood of ongoing use 1 year or more after the prescription of the brace.

  5. Stimulation of Myofibrillar Protein Synthesis in Hindlimb Suspended Rats by Resistance Exercise and Growth Hormone (United States)

    Linderman, Jon K.; Whittall, Justen B.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Booth, Frank W.; Grindeland, Richard E.


    The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85 deg.), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks was determined with a constant infusion of H-3-Leucine at 15', 60', 180', and 360' following exercise. Three days of HLS depressed Ks is approx. equal to 65% and 30-40% in the soleus and gastrocnemius muscles, respectively (p is less than or equal to 0.05). Exercise increased soleus Ks in saline-treated rats 149% 60' following exercise (p less than or equal to 0.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH + exercise increased soleus Ks 84%, 108%, and 72% at 15', 60' and 360' following exercise (p is less than or equal to 0.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360' post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis.

  6. Mechanisms of phloem unloading: shaped by cellular pathways, their conductances and sink function. (United States)

    Milne, Ricky J; Grof, Christopher Pl; Patrick, John W


    Phloem unloading represents a series of cell-to-cell transport steps transferring phloem-mobile constituents from phloem to sink tissues/organs to fuel their development or resource storage. Our analysis focuses on unloading of two major phloem-mobile constituents, sugars and water. Their unloading can occur across phloem plasma membranes (apoplasmic unloading), through plasmodesmata interconnecting phloem and sink cells (symplasmic unloading) or predominately symplasmically with an intervening post-phloem apoplasmic step. In planta studies of phloem unloading encounter substantial technical challenges in accessing phloem within a meshwork of vascular/ground tissues. Thus, current understanding of phloem-unloading mechanisms largely has been deduced from indirect experimental measures or modelling. Here we highlight recent advances in understanding phloem unloading mechanisms and identify where important knowledge gaps remain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Adaptation of bone and tendon to prolonged hindlimb suspension in rats (United States)

    Vailas, Arthur C.; Deluna, Diane M.; Lewis, Lisa L.; Curwin, Sandra L.; Roy, Roland R.


    The effect of a sustained deprivation of ground reaction forces on mineralized and soft connective tissues was investigated in rats subjected to 28-d-long hind-limb suspension. The results of morphological and biochemical studies carried out on femurs and patellar tendons obtained from suspended and nonsuspended 110-d-old rats showed that prolonged suspension led to an increase of the minimum diameter of the femur middiaphysis (by 12 percent), without any significant alterations in cortical area, density, mineral and collagen concentrations, femur wet weight, length, and DNA and uronic acid concentrations. However, in the patellar tendons of suspended rats, the collagen and proteoglycan concentrations were 28 percent lower than in tendons obtained from nonsuspended animals. These results suggest that ground reaction forces are important for the maintenance of cortical bone and patellar tendon homeostasis during weight-bearing conditions.

  8. Phloem unloading in Arabidopsis roots is convective and regulated by the phloem-pole pericycle

    DEFF Research Database (Denmark)

    Ross-Elliott, Timothy J.; Jensen, Kaare Hartvig; Haaning, Katrine S.


    , and mathematical modelling) to show that phloem unloading of solutes in Arabidopsis roots occurs through plasmodesmata by a combination of mass flow and diffusion (convective phloem unloading). During unloading, solutes and proteins are diverted into the phloem-pole pericycle, a tissue connected to the protophloem...

  9. Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer. (United States)

    Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin


    Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (Pcortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential therapeutic candidate to improve the function of lower extremity in patients with spastic hemiplegia. © 2016 The Author(s).

  10. Intermittent fasting in mice does not improve hindlimb motor performance after spinal cord injury. (United States)

    Streijger, Femke; Plunet, Ward T; Plemel, Jason Ryan; Lam, Clarrie K; Liu, Jie; Tetzlaff, Wolfram


    Previously, we reported that every-other-day-fasting (EODF) in Sprague-Dawley rats initiated after cervical spinal cord injury (SCI) effectively promoted functional recovery, reduced lesion size, and enhanced sprouting of the corticospinal tract. More recently, we also showed improved behavioral recovery with EODF after a moderate thoracic contusion injury in rats. In order to make use of transgenic mouse models to study molecular mechanisms of EODF, we tested here whether this intermittent fasting regimen was also beneficial in mice after SCI. Starting after SCI, C57BL/6 mice were fed a standard rodent chow diet either with unrestricted access or feeding every other day. Over a 14-week post-injury period, we assessed hindlimb locomotor function with the Basso Mouse Scale (BMS) open-field test and horizontal ladder, and the spinal cords were evaluated histologically to measure white and grey matter sparing. EODF resulted in an overall caloric restriction of 20% compared to animals fed ad libitum (AL). The EODF-treated animals exhibited a ∼ 14% reduction in body weight compared to AL mice, and never recovered to their pre-operative body weight. In contrast to rats on an intermittent fasting regimen, mice exhibited no increase in blood ketone bodies by the end of the second, third, and fourth day of fasting. EODF had no beneficial effect on tissue sparing and failed to improve behavioral recovery of hindlimb function. Hence this observation stands in stark contrast to our earlier observations in Sprague-Dawley rats. This is likely due to the difference in the metabolic response to intermittent fasting as evidenced by different ketone levels during the first week of the EODF regimen.

  11. Restoration of Hindlimb Movements after Complete Spinal Cord Injury Using Brain-Controlled Functional Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Eric B. Knudsen


    Full Text Available Single neuron and local field potential signals recorded in the primary motor cortex have been repeatedly demonstrated as viable control signals for multi-degree-of-freedom actuators. Although the primary source of these signals has been fore/upper limb motor regions, recent evidence suggests that neural adaptation underlying neuroprosthetic control is generalizable across cortex, including hindlimb sensorimotor cortex. Here, adult rats underwent a longitudinal study that included a hindlimb pedal press task in response to cues for specific durations, followed by brain machine interface (BMI tasks in healthy rats, after rats received a complete spinal transection and after the BMI signal controls epidural stimulation (BMI-FES. Over the course of the transition from learned behavior to BMI task, fewer neurons were responsive after the cue, the proportion of neurons selective for press duration increased and these neurons carried more information. After a complete, mid-thoracic spinal lesion that completely severed both ascending and descending connections to the lower limbs, there was a reduction in task-responsive neurons followed by a reacquisition of task selectivity in recorded populations. This occurred due to a change in pattern of neuronal responses not simple changes in firing rate. Finally, during BMI-FES, additional information about the intended press duration was produced. This information was not dependent on the stimulation, which was the same for short and long duration presses during the early phase of stimulation, but instead was likely due to sensory feedback to sensorimotor cortex in response to movement along the trunk during the restored pedal press. This post-cue signal could be used as an error signal in a continuous decoder providing information about the position of the limb to optimally control a neuroprosthetic device.

  12. Adaptations in muscle activity to induced, short-term hindlimb lameness in trotting dogs.

    Directory of Open Access Journals (Sweden)

    Stefanie Fischer

    Full Text Available Muscle tissue has a great intrinsic adaptability to changing functional demands. Triggering more gradual responses such as tissue growth, the immediate responses to altered loading conditions involve changes in the activity. Because the reduction in a limb's function is associated with marked deviations in the gait pattern, understanding the muscular responses in laming animals will provide further insight into their compensatory mechanisms as well as help to improve treatment options to prevent musculoskeletal sequelae in chronic patients. Therefore, this study evaluated the changes in muscle activity in adaptation to a moderate, short-term, weight-bearing hindlimb lameness in two leg and one back muscle using surface electromyography (SEMG. In eight sound adult dogs that trotted on an instrumented treadmill, bilateral, bipolar recordings of the m. triceps brachii, the m. vastus lateralis and the m. longissimus dorsi were obtained before and after lameness was induced. Consistent with the unchanged vertical forces as well as temporal parameters, neither the timing nor the level of activity changed significantly in the m. triceps brachii. In the ipsilateral m. vastus lateralis, peak activity and integrated SEMG area were decreased, while they were significantly increased in the contralateral hindlimb. In both sides, the duration of the muscle activity was significantly longer due to a delayed offset. These observations are in accordance with previously described kinetic and kinematic changes as well as changes in muscle mass. Adaptations in the activity of the m. longissimus dorsi concerned primarily the unilateral activity and are discussed regarding known alterations in trunk and limb motions.

  13. Extracellular Matrix Hydrogel Promotes Tissue Remodeling, Arteriogenesis, and Perfusion in a Rat Hindlimb Ischemia Model

    Directory of Open Access Journals (Sweden)

    Jessica L. Ungerleider, BS


    Full Text Available Although surgical and endovascular revascularization can be performed in peripheral arterial disease (PAD, 40% of patients with critical limb ischemia do not have a revascularization option. This study examines the efficacy and mechanisms of action of acellular extracellular matrix-based hydrogels as a potential novel therapy for treating PAD. We tested the efficacy of using a tissue-specific injectable hydrogel derived from decellularized porcine skeletal muscle (SKM and compared this to a new human umbilical cord-derived matrix (hUC hydrogel, which could have greater potential for tissue regeneration because of the younger age of the tissue source. In a rodent hindlimb ischemia model, both hydrogels were injected 1-week post-surgery and perfusion was regularly monitored with laser speckle contrast analysis to 35 days post-injection. There were significant improvements in hindlimb tissue perfusion and perfusion kinetics with both biomaterials. Histologic analysis indicated that the injected hydrogels were biocompatible, and resulted in arteriogenesis, rather than angiogenesis, as well as improved recruitment of skeletal muscle progenitors. Skeletal muscle fiber morphology analysis indicated that the muscle treated with the tissue-specific SKM hydrogel more closely matched healthy tissue morphology. Whole transcriptome analysis indicated that the SKM hydrogel caused a shift in the inflammatory response, decreased cell death, and increased blood vessel and muscle development. These results show the efficacy of an injectable ECM hydrogel alone as a potential therapy for treating patients with PAD. Our results indicate that the SKM hydrogel improved functional outcomes through stimulation of arteriogenesis and muscle progenitor cell recruitment.

  14. Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors. (United States)

    DiGiovanna, Jack; Dominici, Nadia; Friedli, Lucia; Rigosa, Jacopo; Duis, Simone; Kreider, Julie; Beauparlant, Janine; van den Brand, Rubia; Schieppati, Marco; Micera, Silvestro; Courtine, Grégoire


    Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor procedures. We found that the activation of hindlimb motor cortex preceded gait initiation. During overground locomotion, the motor cortex exhibited consistent neuronal population responses that were synchronized with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring enhanced muscle activity or skilled paw placement correlated with substantial adjustment in neuronal population responses. In contrast, all rats exhibited a reduction of cortical activity during more automated behavior, such as stepping on a treadmill. Despite the facultative role of the motor cortex in the production of locomotion in rats, these results show that the encoding of hindlimb features in motor cortex dynamics is comparable in rats and cats. However, the extent of motor cortex modulations appears linked to the degree of volitional engagement and complexity of the task, reemphasizing the importance of goal-directed behaviors for motor control studies, rehabilitation, and neuroprosthetics. We mapped the neuronal population responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle synergies across a spectrum of natural locomotion behaviors. Robust task-specific neuronal population responses revealed that the rat motor cortex displays similar modulation as other mammals during locomotion. However, the reduced motor cortex activity during more automated behaviors suggests a relationship between the degree of engagement and task complexity. This relationship

  15. Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse

    Directory of Open Access Journals (Sweden)

    Céline Jean-Xavier


    Full Text Available The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs during drug-induced fictive locomotor-like activity (LLA in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC and hindlimb MNs in lateral motor column (LMC. The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.

  16. Metformin stimulates ischemia-induced revascularization through an eNOS dependent pathway in the ischemic hindlimb mice model. (United States)

    Takahashi, Noriko; Shibata, Rei; Ouchi, Noriyuki; Sugimoto, Masayuki; Murohara, Toyoaki; Komori, Kimihiro


    As first-line treatment for type 2 diabetes, metformin has gained a strong position. In addition, type 2 diabetics benefit from the fact that metformin is associated with a reduction in cardiovascular events. Nevertheless, there is a dearth of information concerning the functional role of metformin in regulating angiogenesis. Our present study explores whether metformin is involved in the modulation of the revascularization processes in vivo by employing a hindlimb mice model of ischemia-induced angiogenesis. For comparative purposes, randomly selected wild-type (WT) mice or endothelial nitric oxide synthase (eNOS) deficient mice were assigned to one of two groups. One group was orally administered a daily dose of metformin through a gastric tube whereas the other group served as a control with no metformin administered. Both groups were subjected to unilateral hindlimb ischemia. Laser Doppler analysis coupled with capillary density staining with CD31was the method employed to determine revascularization. Adenosine monophosphate-activated protein kinase (AMPK) and eNOS phosphorylation levels were assessed using Western blot analysis. Subsequent to hindlimb ischemic surgery, in comparison to the nontreated mice, metformin-treated WT mice showed accelerated limb perfusion, which was substantiated by laser Doppler blood-flow measurements and the presence of increased capillary density in the ischemic adductor muscle. Treatment with metformin significantly enhanced the increase in AMPK and eNOS phosphorylation levels of muscle tissues in WT mice induced by ischemia. In eNOS- deficient knockout mice, there was a significant increase in ischemic tissue AMPK phosphorylation induced by metformin; however, blood flow recovery in ischemic limb after surgery was unaffected. Metformin promoted revascularization in the presence of tissue ischemia through an AMPK/eNOS-related mechanism. Our study indicates that, in addition to its glucose-lowering effect, metformin fosters

  17. Cardiopulmonary and arterial baroreceptor unloading during passive hyperthermia does not contribute to hyperthermia-induced hyperventilation. (United States)

    Lucas, Rebekah A I; Pearson, James; Schlader, Zachary J; Crandall, Craig G


    What is the central question of this study? Does baroreceptor unloading during passive hyperthermia contribute to increases in ventilation and decreases in end-tidal carbon dioxide during that exposure? What is the main finding and its importance? Hyperthermic hyperventilation is not mitigated by expanding central blood volume and reloading the cardiopulmonary baroreceptors via rapid saline infusion or by reloading the arterial baroreceptors via phenylephrine administration. The absence of a reduction in ventilation upon reloading the baroreceptors to pre-hyperthermic levels indicates that cardiopulmonary and arterial baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans. This study tested the hypothesis that baroreceptor unloading during passive hyperthermia contributes to increases in ventilation and decreases in end-tidal partial pressure of carbon dioxide (P ET ,CO2) during that exposure. Two protocols were performed, in which healthy subjects underwent passive hyperthermia (increasing intestinal temperature by ∼1.8°C) to cause a sustained increase in ventilation and reduction in P ET ,CO2. Upon attaining hyperthermic hyperventilation, in protocol 1 (n = 10; three females) a bolus (19 ± 2 ml kg(-1) ) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to restore reductions in central venous pressure, whereas in protocol 2 (n = 11; five females) phenylephrine was infused intravenously (60-120 μg min(-1) ) to return mean arterial pressure to normothermic levels. In protocol 1, hyperthermia increased ventilation (by 2.2 ± 1.7 l min(-1) , P  0.05). In protocol 2, hyperthermia increased ventilation (by 5.0 ± 2.7 l min(-1) , P  0.05). The absence of a reduction in ventilation upon reloading the cardiopulmonary and arterial baroreceptors to pre-hyperthermic levels indicates that baroreceptor unloading with hyperthermia is unlikely to contribute to

  18. New histone supply regulates replication fork speed and PCNA unloading

    DEFF Research Database (Denmark)

    Mejlvang, Jakob; Feng, Yunpeng; Alabert, Constance


    Correct duplication of DNA sequence and its organization into chromatin is central to genome function and stability. However, it remains unclear how cells coordinate DNA synthesis with provision of new histones for chromatin assembly to ensure chromosomal stability. In this paper, we show...... that replication fork speed is dependent on new histone supply and efficient nucleosome assembly. Inhibition of canonical histone biosynthesis impaired replication fork progression and reduced nucleosome occupancy on newly synthesized DNA. Replication forks initially remained stable without activation...... unloading is delayed in the absence of nucleosome assembly. We propose that coupling of fork speed and PCNA unloading to nucleosome assembly provides a simple mechanism to adjust DNA replication and maintain chromatin integrity during transient histone shortage....

  19. Efficacy of Unloader Bracing in Reducing Symptoms of Knee Osteoarthritis. (United States)

    Ostrander, Roger V; Leddon, Charles E; Hackel, Joshua G; O'Grady, Christopher P; Roth, Charles A


    Braces designed to unload the more diseased compartment of the knee have been used to provide symptomatic relief from osteoarthritis (OA). Research on the efficacy of these braces is needed. Thirty-one patients with knee OA were randomized to receive an unloader brace (n = 16) or not to receive a brace (control group, n = 15). Knee Injury and Osteoarthritis Outcomes Score (KOOS) and visual analog scale (VAS) scores were used to evaluate outcomes. KOOS results showed that the brace group had significantly less pain (P knee-related quality of life (P = .718). VAS results showed that the brace group had significantly less pain throughout the day (P = .021) and had improved activity levels (P = .035). There was no difference in ability to sleep (P = .117) or in use of nonsteroidal anti-inflammatory drugs (P = .138). Our study results showed that use of an unloader brace for medial compartment knee OA led to significant improvements in pain, arthritis symptoms, and ability to engage in activities.

  20. Photoplethysmography system for blood pulsation detection in unloaded artery conditions (United States)

    Grabovskis, A.; Marcinkevics, Z.; Rubenis, O.; Rubins, U.; Lusa, V.


    Photoplethysmography (PPG) is an optical method of blood pulsation recording and has been extensively studied for decades. Recently PPG is widely used in the medical equipment for patient monitoring and in laboratories for research and physiological studies. In spite of the technological progress in the field of medical equipment, there are no generally accepted standards for clinical PPG measurements up to date. One of the most important factors affecting PPG waveform is the contact pressure between tissue and PPG probe. The aim of the current study was to develop and evaluate a system for software-assisted PPG signal acquisition from the unloaded artery. Novel PPG waveform derived Optimal Pressure Parameter (OPP) has been proposed as the reliable indicator of unloaded artery condition. We affirm that PPG measurements provided in balanced transmural arterial pressure conditions might serve as a reference for the unification of contact manner optical plethysmography methods. It is a step forward towards the standardization of the PPG methodology, and showed that the maximal value of the OPP, obtained in the particular experimental trial, indicates the optimal PPG probe contact pressure at that moment. Our developed system has been validated in the experimental series and showed the possibility of determining the correct PPG contact pressure value with high repeatability. It is concluded that this system can provide the necessary feedback to perform reliable PPG signal acquisition from the unloaded conduit artery.

  1. Unloaded treadmill training therapy for lumbar disc herniation injury. (United States)

    Simpson, S; Bettis, B; Herbertson, J


    The low back region is an area that is very susceptible to injury in athletes. Running is an activity that can be significantly affected by chronic overuse stress. The athlete presented in this case report suffered a herniation of the disc between L-4 and L-5 while training for and racing in a national championship marathon. The athlete was placed on a treatment program of heat, electrical muscle stimulation, and strength and flexibility exercises. The athlete also continued to train by unloaded treadmill training therapy. Unloaded treadmill training therapy produced an effect that reduced stress on injured joints and tissue. This enabled the athlete to maintain fitness while running pain-free on this specialized equipment. The athlete trained twice a week for 16 weeks and training runs ranged from 3 miles to a half-marathon (13.1 miles). Unloaded amounts decreased from 20 to 3 pounds. Training times improved at all distances and were maintained following resumption of normal training.

  2. Size and myosin heavy chain profiles of rat hindlimb extensor muscle fibers after 2 weeks at 2G. (United States)

    Roy, R R; Roy, M E; Talmadge, R J; Mendoza, R; Grindeland, R E; Vasques, M


    The effects of 14 d of continuous centrifugation at approximately 2G on the hindlimb extensor musculature of male rats were studied. The mean body mass of centrifuged rats was 17% smaller than age-matched controls. In centrifuged rats, the mean absolute masses of the soleus and medial gastrocnemius (MG) were similar to control, while the mean relative masses (expressed as milligram muscle mass/gram of body mass) were larger than control. Based on a battery of monoclonal antibodies for specific myosin heavy chains (MHC), the soleus of centrifuged rats had a lower percentage (68 vs. 74%) of fibers expressing type I MHC only and a higher percentage (15 vs. 10%) that co-expressed type I and IIa MHC's. The MHC composition of fibers from the deep portion of the MG was unaffected by centrifugation. The MHC compositions based on SDS-PAGE gel electrophoresis for each muscle were similar in the two groups. Mean fiber size of each fiber type in the soleus was unaffected by centrifugation. In the MG, the fibers, expressing only type IIb MHC were smaller in the centrifuge compared to control rats. Although 2 weeks of chronic centrifugation at 2G resulted in a cessation of body growth, there was essentially no effect on the muscle masses or fiber size in either a slow or fast extensor muscle. These data suggest that periods of centrifugation may be beneficial in maintaining extensor muscle mass in an animal that is not growing at a normal rate e.g., during chronic unloading.

  3. Percutaneous carbon dioxide treatment using a gas mist generator enhances the collateral blood flow in the ischemic hindlimb. (United States)

    Izumi, Yasukatsu; Yamaguchi, Takehiro; Yamazaki, Takanori; Yamashita, Naoto; Nakamura, Yasuhiro; Shiota, Masayuki; Tanaka, Masako; Sano, Soichi; Osada-Oka, Mayuko; Shimada, Kenei; Wanibuchi, Hideki; Miura, Katsuyuki; Yoshiyama, Minoru; Iwao, Hiroshi


    Highly concentrated carbon dioxide (CO2) is thought to be useful for ischemic diseases. We investigated whether treatment with a few micrometers of CO2 molecules atomized via two fluidnozzles (CO2 mist) exerts an angiogenic effect in a mouse ischemic hindlimb model. Mice with unilateral hindlimb ischemia were divided into untreated (UT), 100% CO2 gas alone-treated (CG), mixed air (O2; 20%, N2; 80%) mist-treated (AM) and 100% CO2 mist-treated (CM) groups. The lower body of the mice was encased in a polyethylene bag filled with each gaseous agent using a gas mist generator for 10 minutes daily. According to a laser Doppler analysis, the ischemic hindlimb blood flow was persistently higher after the seventh day of induction of ischemia in the CM group than in the UT group. The capillary density was also greater in the CM group on day 28 compared with that observed in the UT group. In addition, the parameters in the AM and CG groups were similar to those obtained in the UT group. The observed effects were abolished by the administration of an inhibitor of nitric oxide synthase (NOS). The vascular endothelial growth factor mRNA expression and protein levels and the phosphorylated endothelial NOS level were increased in the CM group compared with that observed in the UT group. A proteomic analysis using liquid chromatography-tandem mass spectrometry identified novel protein candidates regulated by CO2 mist. Percutaneous CO2 mist therapy may be useful for treating ischemia-induced angiogenesis.

  4. Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury. (United States)

    West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V


    Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day(-1), 5 days week(-1) for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.

  5. Differential effects of brain-derived neurotrophic factor and neurotrophin-3 on hindlimb function in paraplegic rats. (United States)

    Boyce, Vanessa S; Park, Jihye; Gage, Fred H; Mendell, Lorne M


    We compared the effect of viral administration of brain-derived neurotrophic factor (BDNF) or neurotrophin 3 (NT-3) on locomotor recovery in adult rats with complete thoracic (T10) spinal cord transection injuries, in order to determine the effect of chronic neurotrophin expression on spinal plasticity. At the time of injury, BDNF, NT-3 or green fluorescent protein (GFP) (control) was delivered to the lesion via adeno-associated virus (AAV) constructs. AAV-BDNF was significantly more effective than AAV-NT-3 in eliciting locomotion. In fact, AAV-BDNF-treated rats displayed plantar, weight-supported hindlimb stepping on a stationary platform, that is, without the assistance of a moving treadmill and without step training. Rats receiving AAV-NT-3 or AAV-GFP were incapable of hindlimb stepping during this task, despite provision of balance support. AAV-NT-3 treatment did promote the recovery of treadmill-assisted stepping, but this required continuous perineal stimulation. In addition, AAV-BDNF-treated rats were sensitized to noxious heat, whereas AAV-NT-3-treated and AAV-GFP-treated rats were not. Notably, AAV-BDNF-treated rats also developed hindlimb spasticity, detracting from its potential clinical applicability via the current viral delivery method. Intracellular recording from triceps surae motoneurons revealed that AAV-BDNF significantly reduced motoneuron rheobase, suggesting that AAV-BDNF promoted the recovery of over-ground stepping by enhancing neuronal excitability. Elevated nuclear c-Fos expression in interneurons located in the L2 intermediate zone after AAV-BDNF treatment indicated increased activation of interneurons in the vicinity of the locomotor central pattern generator. AAV-NT-3 treatment reduced motoneuron excitability, with little change in c-Fos expression. These results support the potential for BDNF delivery at the lesion site to reorganize locomotor circuits. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of

  6. Autophagy Plays an Essential Role in Mediating Regression of Hypertrophy during Unloading of the Heart (United States)

    Hariharan, Nirmala; Ikeda, Yoshiyuki; Hong, Chull; Alcendor, Ralph R.; Usui, Soichiro; Gao, Shumin; Maejima, Yasuhiro; Sadoshima, Junichi


    Autophagy is a bulk degradation mechanism for cytosolic proteins and organelles. The heart undergoes hypertrophy in response to mechanical load but hypertrophy can regress upon unloading. We hypothesize that autophagy plays an important role in mediating regression of cardiac hypertrophy during unloading. Mice were subjected to transverse aortic constriction (TAC) for 1 week, after which the constriction was removed (DeTAC). Regression of cardiac hypertrophy was observed after DeTAC, as indicated by reduction of LVW/BW and cardiomyocyte cross-sectional area. Indicators of autophagy, including LC3-II expression, p62 degradation and GFP-LC3 dots/cell, were significantly increased after DeTAC, suggesting that autophagy is induced. Stimulation of autophagy during DeTAC was accompanied by upregulation of FoxO1. Upregulation of FoxO1 and autophagy was also observed in vitro when cultured cardiomyocytes were subjected to mechanical stretch followed by incubation without stretch (de-stretch). Transgenic mice with cardiac-specific overexpression of FoxO1 exhibited smaller hearts and upregulation of autophagy. Overexpression of FoxO1 in cultured cardiomyocytes significantly reduced cell size, an effect which was attenuated when autophagy was inhibited. To further examine the role of autophagy and FoxO1 in mediating the regression of cardiac hypertrophy, beclin1+/− mice and cultured cardiomyocytes transduced with adenoviruses harboring shRNA-beclin1 or shRNA-FoxO1 were subjected to TAC/stretch followed by DeTAC/de-stretch. Regression of cardiac hypertrophy achieved after DeTAC/de-stretch was significantly attenuated when autophagy was suppressed through downregulation of beclin1 or FoxO1. These results suggest that autophagy and FoxO1 play an essential role in mediating regression of cardiac hypertrophy during mechanical unloading. PMID:23308102

  7. Towards a rational use of loading and unloading areas in urban environments (United States)

    Barba, Daniel; Garcia-Villanueva, Sergio; Del-Campo-Pardo, Hector; March, Juan A.; Llanos, Diego R.


    Despite the efforts of the authorities, that promote the use of alternative transportation systems, the traffic still increases in European cities, leading not only to traffic jams but also to pollution episodes. Delivery vehicles are part of both problems, because of their intensive use, the advent of e-commerce, the limited number and sizes of loading and unloading areas in many ancient European cities, and the difficulties associated to keep track of the correct use of these spaces. In this work we propose an holistic solution to the management of delivery vehicles in urban environments. Our solution, called RYDER, is based on the use of BLE (Bluetooth Low Energy) devices that should be provided by the local authority to delivery vehicles, as part of their authorization to use the loading and unloading areas. With the help of low-cost, low-power antennas with Bluetooth and 4G capabilities installed next to each loading/unloading area, the authorities are able to know in real time (a) the use of these areas by delivery vehicles, (b) the paths of the vehicles while they travel across the city, (c) the time spent in each area by each one of them, and (d) with the help of a mobile/tablet App, the local Police can check in seconds the permissions of each vehicle using these public spaces. Moreover, the use of a GIS-based platform allows the Traffic Department to track online each particular vehicle, based on the loading/unloading spaces being used, and to infer the most representative paths they follow, an information that may guide the decision about where these spaces are really necessary and whether each particular vehicle follows their associated usage rules. The deployment of RYDER low-cost antennas can also serve for other purposes, such as to track the routes followed by public loan bicycles, or by other fleets of public vehicles. With the help of low-cost sensors, antennas can also return an estimation of pollution values, such as levels of ozone, particulate

  8. Assessment of hindlimb locomotor strength in spinal cord transected rats through animal-robot contact force. (United States)

    Nessler, Jeff A; Moustafa-Bayoumi, Moustafa; Soto, Dalziel; Duhon, Jessica; Schmitt, Ryan


    Robotic locomotor training devices have gained popularity in recent years, yet little has been reported regarding contact forces experienced by the subject performing automated locomotor training, particularly in animal models of neurological injury. The purpose of this study was to develop a means for acquiring contact forces between a robotic device and a rodent model of spinal cord injury through instrumentation of a robotic gait training device (the rat stepper) with miniature force/torque sensors. Sensors were placed at each interface between the robot arm and animal's hindlimb and underneath the stepping surface of both hindpaws (four sensors total). Twenty four female, Sprague-Dawley rats received mid-thoracic spinal cord transections as neonates and were included in the study. Of these 24 animals, training began for 18 animals at 21 days of age and continued for four weeks at five min/day, five days/week. The remaining six animals were untrained. Animal-robot contact forces were acquired for trained animals weekly and untrained animals every two weeks while stepping in the robotic device with both 60 and 90% of their body weight supported (BWS). Animals that received training significantly increased the number of weight supported steps over the four week training period. Analysis of raw contact forces revealed significant increases in forward swing and ground reaction forces during this time, and multiple aspects of animal-robot contact forces were significantly correlated with weight bearing stepping. However, when contact forces were normalized to animal body weight, these increasing trends were no longer present. Comparison of trained and untrained animals revealed significant differences in normalized ground reaction forces (both horizontal and vertical) and normalized forward swing force. Finally, both forward swing and ground reaction forces were significantly reduced at 90% BWS when compared to the 60% condition. These results suggest that

  9. Spinal shrinkage in unloaded and loaded drop-jumping. (United States)

    Fowler, N E; Lees, A; Reilly, T


    Plyometric activities, engaging the muscle in a stretch-shortening cycle, are widely used in athletic training. One such plyometric exercise is drop-jumping, where the athlete drops from a raised platform and immediately on landing performs a maximal vertical jump. These actions are also performed with the athlete externally loaded by the addition of weights to provide greater resistance. Exercises which involve repeated impacts have been shown to give rise to a loss of stature (shrinkage) which can be measured by means of a sensitive stadiometer. This study examined the shrinkage induced by unloaded and loaded drop-jumping from a height of 26 cm. Eight male subjects, aged 20-24 years, performed the test protocol three times, at the same time of day on each occasion. Fifty drop-jumps from a height of 26 cm were performed with no additional load and with a load of 8.5 kg carried in a weighted vest. The third condition was a standing trial where the subject stood for 10 min (the time taken to perform the jumps) wearing the weighted vest. Stature was measured before exercise, immediately after exercise and after a 20 min standing recovery. On a separate occasion the regimen was performed and the vertical reaction force was measured using a Kistler force platform. The mean change in stature for the two jump conditions showed shrinkages of 0.62 (+/- 0.43) mm for unloaded and 2.14 (+/- 1.56) mm for the loaded (p < 0.05). The variance in shrinkage was greater in the loaded case compared to the unloaded condition (p < 0.05) indicating a wider range of jumping strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Propofol injection combined with bone marrow mesenchymal stem cell transplantation better improves electrophysiological function in the hindlimb of rats with spinal cord injury than monotherapy. (United States)

    Wang, Yue-Xin; Sun, Jing-Jing; Zhang, Mei; Hou, Xiao-Hua; Hong, Jun; Zhou, Ya-Jing; Zhang, Zhi-Yong


    The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

  11. Research on automatic loading & unloading technology for vertical hot ring rolling process

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    Xiaokai Wang


    Full Text Available The automatic loading & unloading technology is the key to the automatic ring production line. In this paper, the automatic vertical hot ring rolling (VHRR process is taken as the target, the method of the loading & unloading for VHRR is proposed, and the mechanical structure of loading & unloading system is designed, The virtual prototype model of VHRR mill and loading & unloading mechanism is established, and the coordinated control method of VHRR mill and loading & unloading auxiliaries is studied, the movement trace and dynamic characteristic of the critical components are obtained. Finally, a series of hot ring rolling tests are conducted on the VHRR mill, and the production rhythm and the formed rings' geometric precision are analysed. The tests results show that the loading & unloading technology can meet the high quality and high efficiency ring production requirement. The research conclusions have practical significance for the large-scale automatic ring production.

  12. Is valgus unloader bracing effective in normally aligned individuals: implications for post-surgical protocols following cartilage restoration procedures. (United States)

    Orishimo, Karl F; Kremenic, Ian J; Lee, Steven J; McHugh, Malachy P; Nicholas, Stephen J


    Utilizing valgus unloader braces to reduce medial compartment loading in patients undergoing cartilage restoration procedures may be an alternative to non-weightbearing post-operative protocols in these patients. It was hypothesized that valgus unloader braces will reduce knee adduction moment during the stance phase in healthy subjects with normal knee alignment. Gait analysis was performed on twelve adult subjects with normal knee alignment and no history of knee pathology. Subjects were fitted with an off-the-shelf adjustable valgus unloader brace and tested under five conditions: one with no brace and four with increasing valgus force applied by the brace. Frontal and sagittal plane knee angles and external moments were calculated during stance via inverse dynamics. Analyses of variance were used to assess the effect of the brace conditions on frontal and sagittal plane joint angles and moments. With increasing tension in the brace, peak frontal plane knee angle during stance shifted from 1.6° ± 4.2° varus without the brace to 4.1° ± 3.6° valgus with maximum brace tension (P = 0.02 compared with the no brace condition). Peak knee adduction moment and knee adduction impulse decreased with increasing brace tension (main effect of brace, P knee biomechanics were minimally affected. The use of these braces following a cartilage restoration procedure may provide adequate protection of the repair site without limiting the patient's mobility.

  13. Effects of protein-deficient nutrition during rat pregnancy and development on developmental hindlimb crossing due to methylmercury intoxication. (United States)

    Chakrabarti, S K; Bai, C


    Pregnant rats were fed either a control (20% protein) or low (3.5%) protein diet during gestation and lactation. The pups were separated from their mothers on postnatal day 21, and were given the same diet as their corresponding mothers. The groups of pups from each diet group were treated on either postnatal day 21 or postnatal day 60 with 7.5 mg methylmercury chloride (MeHgCl) per kg b.w. once daily by gavage for 10 consecutive days, and the development of ataxia (hind-limb crossing) was monitored. The offspring from mothers on the protein-deficient diet were found to be more sensitive to MeHg-induced ataxia than those on the protein-sufficient diet. The former accumulated more mercury in different brain regions than the latter. The rates of protein synthesis in different brain regions of the offspring fed the protein-deficient diet were significantly reduced compared with the rates in those fed the protein-sufficient diet. However, MeHg treatment did not significantly modify the rates of such protein synthesis further in protein-deficient rats. Thus, a significantly much higher inhibition of the intrinsic rates of protein synthesis in different brain regions due to severe protein deficiency, as observed in this study, may be partly responsible for the increased susceptibility of developing rats fed a protein-deficient diet to MeHg-induced ataxia, or hindlimb crossing, although other factor(s) might also be involved.

  14. Effects of protein-deficient nutrition during rat pregnancy and development on developmental hindlimb crossing due to methylmercury intoxication

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    Chakrabarti, S.K.; Bai, Chengjiang [Montreal Univ., Quebec (Canada). Dept. de Medecine du Travail et Hygiene du Milieu


    Pregnant rats were fed either a control (20% protein) or low (3.5%) protein diet during gestation and lactation. The pups were separated from their mothers on postnatal day 21, and were given the same dient as their corresponding mothers. The groups of pups from each diet group were treated on either postnatal day 21 or postnatal day 60 with 7.5 mg methylmercury chloride (MeHgCl) per kg b.w. once daily by gavage for 10 consecutive days, and the development of ataxia (hind-limb corossing) was monitored. The offspring from mothers on the protein-deficient diet were found to be more sensitive to MeHg-induced ataxia than those on the protein-sufficient diet. The former accumulated more mercury in different brain regions than the latter. The rates of protein synthesis in different brain regions of the offspring fed the protein-deficient diet were significantly reduced compared with the rates in those fed the protein-sufficient diet. However, MeHg treatment did not significantly modify the rates of such protein synthesis further in protein-deficient rats. Thus, a significantly much higher inhibition of the intrinsic rates of protein synthesis in different brain regions due to severe protein deficiency, as observed in this study, may be partly responsible for the increased susceptibility of developing rats fed a protein-deficient diet to MeHg-induced ataxia, or hindlimb crossing, although other factor(s) might also be involved. (orig.)

  15. Biomedical analysis of rat body hair after hindlimb suspension for 14 days (United States)

    Terada, Masahiro; Kawano, Fuminori; Ishioka, Noriaki; Higashibata, Akira; Majima, Hideyuki J.; Yamazaki, Takashi; Watanabe-Asaka, Tomomi; Niihori, Maki; Nakao, Reiko; Yamada, Shin; Mukai, Chiaki; Ohira, Yoshinobu


    The levels of 26 minerals in rat body hair were analyzed in control and hindlimb-suspended Wistar Hannover rats (n=5 each). We quantified the levels of 22 minerals in this experiment. However, we were unable to measure the levels of 4 minerals (Be, V, Cd, and Hg) quantitatively because they were below the limit of detection. Of the 22 quantified, the levels of 19 minerals were not significantly different between control and hindlimb-suspended groups. The levels of 3 minerals (Pb, Cr, and Al) tended to be higher in the hindlimb-suspended group than in the control group; however, this difference was not significant. The concentrations of 3 other minerals (I, K, and Mg) were significantly different between the 2 groups. The iodine (I) level was 58.2% higher in the hindlimb-suspended group than in the control group (Pphysiological change in mineral metabolism resulting from physical or mental stress, such as hindlimb suspension, is reflected in body hair. The Japan Aerospace Exploration Agency (JAXA) has initiated a human research study to investigate the effects of long-term space flight on gene expression and mineral metabolism by analyzing hair samples of astronauts who stayed in the International Space Station (ISS) for 6 months. We believe that hindlimb suspension for 14 days can simulate the effects of an extremely severe environment, such as space flight, because the hindlimb suspension model elicits a rapid physiological change in skeletal muscle, bone, and fluid shift even in the short term. These results also suggest that we can detect various effects on the body by analyzing the human scalp hair shaft.

  16. Alterations in Muscle Mass and Contractile Phenotype in Response to Unloading Models: Role of Transcriptional/Pretranslational Mechanisms

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    Kenneth M Baldwin


    Full Text Available Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a muscle unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s. Hence, this review will examine findings from three different animal models of unloading: 1 space flight (SF, i.e., microgravity; 2 hindlimb suspension (HS, a procedure that chronically eliminates weight bearing of the lower limbs; and 3 spinal cord isolation (SI, a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: 1 all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; 2 transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and 3 signaling pathways impacting these alterations appear to be similar in each of the models

  17. Cargo Loading and Unloading Efficiency Analysis in Multimodal Transport

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    Rafał Burdzik


    Full Text Available The paper presents assessment of the impact of the processes handling efficiency on the transport process based on research done in the real object, using same technologies and material handling equipment. The aim of the paper was to confirm importance of loading and unloading processes of palletized cargo as an initial and final link of multimodal transport by developing methods’ proposal for monitoring and assessing the effectiveness of cargo operations as well as development of measures and comparison estimators. The analysis of the manipulation operations’ duration throughout the transport process is based on the percentile rates of manipulation and carriage in total transport process duration and the percentage of manipulating time in the duration of the carriage. These indicators and examined loading and unloading times, are the basis for the development of scheduling algorithms for optimizing transport processes on the scale of the whole transport chain. This data is also a helpful input to support strategic decisions on the allocation of financial resources for the development of infrastructure and terminal equipment, warehouses and other facilities.

  18. Myocardial reverse remodeling after pressure unloading is associated with maintained cardiac mechanoenergetics in a rat model of left ventricular hypertrophy. (United States)

    Ruppert, Mihály; Korkmaz-Icöz, Sevil; Li, Shiliang; Németh, Balázs Tamás; Hegedűs, Péter; Brlecic, Paige; Mátyás, Csaba; Zorn, Markus; Merkely, Béla; Karck, Matthias; Radovits, Tamás; Szabó, Gábor


    Pressure unloading represents the only effective therapy in increased afterload-induced left ventricular hypertrophy (LVH) as it leads to myocardial reverse remodeling (reduction of increased left ventricular mass, attenuated myocardial fibrosis) and preserved cardiac function. However, the effect of myocardial reverse remodeling on cardiac mechanoenergetics has not been elucidated. Therefore, we aimed to provide a detailed hemodynamic characterization in a rat model of LVH undergoing pressure unloading. Pressure overload was induced in Sprague-Dawley rats by abdominal aortic banding for 6 (AB 6th wk) or 12 wk (AB 12th wk). Sham-operated animals served as controls. Aortic debanding procedure was performed after the 6th experimental week (debanded 12th wk) to investigate the regression of LVH. Pressure unloading resulted in significant reduction of LVH (heart weight-to-tibial length ratio: 0.38 ± 0.01 vs. 0.58 ± 0.02 g/mm, cardiomyocyte diameter: 18.3 ± 0.1 vs. 24.1 ± 0.8 μm debanded 12th wk vs. AB 12th wk, P cardiac mechanoenergetics. Copyright © 2016 the American Physiological Society.

  19. Angiogenic Mechanisms of Human CD34+ Stem Cell Exosomes in the Repair of Ischemic Hindlimb. (United States)

    Mathiyalagan, Prabhu; Liang, Yaxuan; Kim, David; Misener, Sol; Thorne, Tina; Kamide, Christine E; Klyachko, Ekaterina; Losordo, Douglas W; Hajjar, Roger J; Sahoo, Susmita


    Paracrine secretions seem to mediate therapeutic effects of human CD34+ stem cells locally transplanted in patients with myocardial and critical limb ischemia and in animal models. Earlier, we had discovered that paracrine secretion from human CD34+ cells contains proangiogenic, membrane-bound nanovesicles called exosomes (CD34Exo). Here, we investigated the mechanisms of CD34Exo-mediated ischemic tissue repair and therapeutic angiogenesis by studying their miRNA content and uptake. When injected into mouse ischemic hindlimb tissue, CD34Exo, but not the CD34Exo-depleted conditioned media, mimicked the beneficial activity of their parent cells by improving ischemic limb perfusion, capillary density, motor function, and their amputation. CD34Exo were found to be enriched with proangiogenic miRNAs such as miR-126-3p. Knocking down miR-126-3p from CD34Exo abolished their angiogenic activity and beneficial function both in vitro and in vivo. Interestingly, injection of CD34Exo increased miR-126-3p levels in mouse ischemic limb but did not affect the endogenous synthesis of miR-126-3p, suggesting a direct transfer of stable and functional exosomal miR-126-3p. miR-126-3p enhanced angiogenesis by suppressing the expression of its known target, SPRED1, simultaneously modulating the expression of genes involved in angiogenic pathways such as VEGF (vascular endothelial growth factor), ANG1 (angiopoietin 1), ANG2 (angiopoietin 2), MMP9 (matrix metallopeptidase 9), TSP1 (thrombospondin 1), etc. Interestingly, CD34Exo, when treated to ischemic hindlimbs, were most efficiently internalized by endothelial cells relative to smooth muscle cells and fibroblasts, demonstrating a direct role of stem cell-derived exosomes on mouse endothelium at the cellular level. Collectively, our results have demonstrated a novel mechanism by which cell-free CD34Exo mediates ischemic tissue repair via beneficial angiogenesis. Exosome-shuttled proangiogenic miRNAs may signify amplification of stem

  20. Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

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    Takhtfooladi, Hamed Ashrafzadeh; Asl, Adel Haghighi Khiabanian [Department of Pathobiology, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shahzamani, Mehran [Department of Cardiovascular Surgery, Isfahan University of Medical Sciences, Tehran (Iran, Islamic Republic of); Takhtfooladi, Mohammad Ashrafzadeh, E-mail: [Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Allahverdi, Amin [Department of Surgery, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Khansari, Mohammadreza [Department of Physiology, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)


    Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries. This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination. The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II. From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

  1. Distal hindlimb kinematics of galloping Thoroughbred racehorses on dirt and synthetic racetrack surfaces. (United States)

    Symons, J E; Garcia, T C; Stover, S M


    The effect of racetrack surface (dirt or synthetic) on distal hindlimb kinematics of racehorses running at competition speeds is not known. To compare distal hindlimb and hoof kinematics during stance of breezing (unrestrained gallop) racehorses between dirt and synthetic surfaces. Two-dimensional kinematic video analysis of 5 Thoroughbred racehorses galloping at high speeds (12-17 m/s) on a dirt racetrack and a synthetic racetrack. The positions of kinematic markers applied to the left hindlimb were recorded at 500 Hz. Position, velocity and acceleration of joint angles and hoof translation during stance were calculated in the sagittal plane. Peak translational and angular kinematic values were compared between the dirt and synthetic race surfaces using mixed model analyses of covariance. Maximum and heel-strike metatarsophalangeal (fetlock) angles were greater (Pfetlock angle occurred earlier during stance on the dirt surface (Pfetlock hyperextension and horizontal hoof slide are greater on a dirt surface than on a synthetic surface. Synthetic race surfaces may mitigate risk of injury to hindlimb fetlock structures by reducing fetlock hyperextension and associated strains in fetlock support structures. Differences in hoof slide may contribute to different distal hindlimb kinematics between surfaces. © 2013 EVJ Ltd.

  2. Does an unloader brace reduce knee loading in normally aligned knees? (United States)

    Ebert, Jay R; Hambly, Karen; Joss, Brendan; Ackland, Timothy R; Donnelly, Cyril J


    Unloading knee braces often are used after tibiofemoral articular cartilage repair. However, the experimental basis for their use in patients with normal tibiofemoral alignment such as those undergoing cartilage repair is lacking. The purpose of this study was to investigate the effect of varus and valgus adjustments to one commercially available unloader knee brace on tibiofemoral joint loading and knee muscle activation in populations with normal knee alignment. The gait of 20 healthy participants (mean age 28.3 years; body mass index 22.9 kg/m(2)) was analyzed with varus and valgus knee brace conditions and without a brace. Spatiotemporal variables were calculated as were knee adduction moments and muscle activation during stance. A directed cocontraction ratio was also calculated to investigate the relative change in the activation of muscles with medial (versus lateral) moment arms about the knee. Group differences were investigated using analysis of variance. The numbers available would have provided 85% power to detect a 0.05 increase or decrease in the knee adduction moment (Nm/kg*m) in the braced condition compared with the no brace condition. With the numbers available, there were no differences between the braced and nonbraced conditions in kinetic or muscle activity parameters. Both varus (directed cocontraction ratio 0.29, SD 0.21, effect size 0.95, p = 0.315) and valgus (directed cocontraction ratio 0.28, SD 0.24, effect size 0.93, p = 0.315) bracing conditions increased the relative activation of muscles with lateral moment arms compared with no brace (directed cocontraction ratio 0.49, SD 0.21). Results revealed inconsistencies in knee kinetics and muscle activation strategies after varus and valgus bracing conditions. Although in this pilot study the results were not statistically significant, the magnitudes of the observed effect sizes were moderate to large and represent suitable pilot data for future work. Varus bracing increased knee

  3. A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation.

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    Andreas Schaefer

    Full Text Available Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC and heterotopic heart transplantation (hHTx in rats.To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations.50 TAC procedures were performed with a survival of 92% (46/50. When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm² (p = 0.001 after three weeks with a fractional shortening (FS of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01. Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001 and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001. Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46. All transplanted organs survived two weeks of mechanical unloading.Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure.

  4. Synergistic effect of using a transcutaneous electrical joint stimulator and an unloading brace in treating osteoarthritis of the knee. (United States)

    Hungerford, David S; Maclaughlin, Edmund J; Mines, Craig M; Deveshwar, Shaili; Elliott, Cynthia; Tuber, Jack S; Principe, John R; Ford, Theresa Lawrence; Schechtman, Joy; Zizic, Thomas M


    Medical treatments and less invasive surgical approaches for knee osteoarthritis are variably effective, and total knee arthroplasty (TKA) is generally reserved for the most severe cases. The care gap between more conservative treatments and TKA leaves many patients with unresolved pain and loss of function for long periods. We conducted a study to determine if incorporating the BioniCare stimulator into an unloading brace would produce more rapid improvement and result in increased adherence and efficacy. Two hundred eighty-nine patients treated only with BioniCare served as historical controls and were compared with 225 patients treated with BioniCare combined with an unloading brace. Means and standard deviations of the changes in scores for pain intensity in the past 48 hours, pain and associated symptoms, patient global assessment, pain on going up or down stairs, and pain on walking on a flat surface and the effect sizes at 1, 3, 6, and 12 months, as well as the percentages of patients achieving at least 20% improvement, and at least 50% improvement, demonstrated that treatment with stimulator and unloading brace combined was significantly superior to treatment with the stimulator alone.

  5. Electromyographic responses from the hindlimb muscles of the decerebrate cat to horizontal support surface perturbations. (United States)

    Honeycutt, Claire F; Gottschall, Jinger S; Nichols, T Richard


    The sensory and neural mechanisms underlying postural control have received much attention in recent decades but remain poorly understood. Our objectives were 1) to establish the decerebrate cat as an appropriate model for further research into the sensory mechanisms of postural control and 2) to observe what elements of the postural response can be generated by the brain stem and spinal cord. Ten animals were decerebrated using a modified premammillary technique, which consists of a premammillary decerebration that is modified with a vertical transection near the subthalamic nucleus to eliminate spontaneous locomotion. Horizontal support surface perturbations were applied to all four limbs and electromyographic recordings were collected from 14 muscles of the right hindlimb. Muscle activation was quantified with tuning curves, which compared increases and decreases in muscle activity to background and graphed the difference against perturbation direction. Parallels were drawn between these tuning curves, which were further quantified with a principal direction and breadth (range of directions of muscle activation), and data collected by other researchers from the intact animal. We found a strong similarity in the direction and breadth of the tuning curves generated in the decerebrate and intact cat. These results support our hypothesis that directionally specific tuning of muscles in response to support surface perturbations does not require the cortex, further indicating a strong role for the brain stem and spinal cord circuits in mediating directionally appropriate muscle activation patterns.

  6. Evaluation of Impulse Unloading Efficiency Pertaining to APS Power Block Turbine for Higher Dynamic Steadiness

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    Yu. Filipchik


    Full Text Available The paper considers the influence of impulse unloading of APS power block turbine on its dynamic steadiness. The performed calculations while simulating four various impulse turbine characteristics have shown that the highest effect is obtained while characteristics of APS power block turbine are close to the characteristics of a steam turbine K-300/240. It has been established that an application of standard time interval for emergency automation startup and existing delay in the operation of electro-hydraulic transformer do not allow to influence on acceleration area and the positive effect due to load shedding is reached only due to an increase of braking site. While decreasing time period for control signal supply from 0,2 sec to 0,1 sec it is possible to increase steadiness by 10 %  for impulse characteristics of APS power blocks and by 39,9–42,6 % – for characteristics of the turbine K-300/240.

  7. Effects of Unloaded vs. Loaded Plyometrics on Speed and Power Performance of Elite Young Soccer Players

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    Ronaldo Kobal


    Full Text Available The purpose of this study was to investigate the effects of loaded and unloaded plyometric training strategies on speed and power performance of elite young soccer players. Twenty-three under-17 male soccer players (age: 15.9 ± 1.2 years, height: 178.3 ± 8.1 cm, body-mass (BM: 68.1 ± 9.3 kg from the same club took part in this study. The athletes were pair-matched in two training groups: loaded vertical and horizontal jumps using an haltere type handheld with a load of 8% of the athletes' body mass (LJ; n = 12 and unloaded vertical and horizontal plyometrics (UJ; n = 11. Sprinting speeds at 5-, 10-, and 20-m, mean propulsive power (MPP relative to the players' BM in the jump squat exercise, and performance in the squat jump (SJ and countermovement jump (CMJ were assessed pre- and post-training period. During the experimental period, soccer players performed 12 plyometric training sessions across a 6-week preseason period. Magnitude based inferences and standardized differences were used for statistical analysis. A very likely increase in the vertical jumps was observed for the LJ group (99/01/00 and 98/02/00 for SJ and CMJ, respectively. In the UJ group a likely increase was observed for both vertical jumps (83/16/01 and 90/10/00, for SJ and CMJ, respectively. An almost certainly decrease in the sprinting velocities along the 20-m course were found in the LJ group (00/00/100 for all split distances tested. Meanwhile, in the UJ likely to very likely decreases were observed for all sprinting velocities tested (03/18/79, 01/13/86, and 00/04/96, for velocities in 5-, 10-, and 20-m, respectively. No meaningful differences were observed for the MPP in either training group (11/85/04 and 37/55/08 for LJ and UJ, respectively. In summary, under-17 professional soccer players increased jumping ability after a 6-week preseason training program, using loaded or unloaded jumps. Despite these positive adaptations, both plyometric strategies failed to

  8. Vestibular nucleus neurons respond to hindlimb movement in the conscious cat (United States)

    Miller, Derek M.; DeMayo, William M.; Bourdages, George H.


    The limbs constitute the sole interface with the ground during most waking activities in mammalian species; it is therefore expected that somatosensory inputs from the limbs provide important information to the central nervous system for balance control. In the decerebrate cat model, the activity of a subset of neurons in the vestibular nuclei (VN) has been previously shown to be modulated by hindlimb movement. However, decerebration can profoundly alter the effects of sensory inputs on the activity of brain stem neurons, resulting in epiphenomenal responses. Thus, before this study, it was unclear whether and how somatosensory inputs from the limb affected the activity of VN neurons in conscious animals. We recorded brain stem neuronal activity in the conscious cat and characterized the responses of VN neurons to flexion and extension hindlimb movements and to whole body vertical tilts (vestibular stimulation). Among 96 VN neurons whose activity was modulated by vestibular stimulation, the firing rate of 65 neurons (67.7%) was also affected by passive hindlimb movement. VN neurons in conscious cats most commonly encoded hindlimb movement irrespective of the direction of movement (n = 33, 50.8%), in that they responded to all flexion and extension movements of the limb. Other VN neurons overtly encoded information about the direction of hindlimb movement (n = 27, 41.5%), and the remainder had more complex responses. These data confirm that hindlimb somatosensory and vestibular inputs converge onto VN neurons of the conscious cat, suggesting that VN neurons integrate somatosensory inputs from the limbs in computations that affect motor outflow to maintain balance. PMID:27440244

  9. Remodeling the Dendritic Spines in the Hindlimb Representation of the Sensory Cortex after Spinal Cord Hemisection in Mice.

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    Kexue Zhang

    Full Text Available Spinal cord injury (SCI can induce remodeling of multiple levels of the cerebral cortex system especially in the sensory cortex. The aim of this study was to assess, in vivo and bilaterally, the remodeling of dendritic spines in the hindlimb representation of the sensory cortex after spinal cord hemisection. Thy1-YFP transgenic mice were randomly divided into the control group and the SCI group, and the spinal vertebral plates (T11-T12 of all mice were excised. Next, the left hemisphere of the spinal cord (T12 was hemisected in the SCI group. The hindlimb representations of the sensory cortex in both groups were imaged bilaterally on the day before (0d, and three days (3d, two weeks (2w, and one month (1m after the SCI. The rates of stable, newly formed, and eliminated spines were calculated by comparing images of individual dendritic spine in the same areas at different time points. In comparison to the control group, the rate of newly formed spines in the contralateral sensory cortex of the SCI group increased at three days and two weeks after injury. The rates of eliminated spines in the bilateral sensory cortices increased and the rate of stable spines in the bilateral cortices declined at two weeks and one month. From three days to two weeks, the stable rates of bilaterally stable spines in the SCI group decreased. In comparison to the control group and contralateral cortex in the SCI group, the re-emerging rate of eliminated spines in ipsilateral cortex of the SCI group decreased significantly. The stable rates of newly formed spines in bilateral cortices of the SCI group decreased from two weeks to one month. We found that the remodeling in the hindlimb representation of the sensory cortex after spinal cord hemisection occurred bilaterally. This remodeling included eliminating spines and forming new spines, as well as changing the reorganized regions of the brain cortex after the SCI over time. Soon after the SCI, the cortex was remodeled

  10. 76 FR 13313 - Hazardous Materials: Cargo Tank Motor Vehicle Loading and Unloading Operations (United States)


    ... hazardous material incident data. The proposal aims to reduce the overall number of hazardous material... practices for loading and unloading operations involving bulk packagings used to transport hazardous... applicable to bulk loading and unloading operations, summarized the results of a public workshop PHMSA hosted...

  11. 15 CFR 758.5 - Conformity of documents and unloading of items. (United States)


    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Conformity of documents and unloading... REGULATIONS EXPORT CLEARANCE REQUIREMENTS § 758.5 Conformity of documents and unloading of items. (a) Purpose... country other than that of the ultimate consignee as stated on the export license. (b) Conformity of...

  12. 76 FR 27300 - Hazardous Materials: Cargo Tank Motor Vehicle Loading and Unloading Operations (United States)


    ... Materials: Cargo Tank Motor Vehicle Loading and Unloading Operations AGENCY: Pipeline and Hazardous..., Routing Symbol M-30, 1200 New Jersey Avenue, SE., Washington, DC 20590. Hand Delivery: To Docket...: Assess the risks of loading and unloading operations and develop written operating procedures based on...

  13. Unloading at Cointrin Airport of the IBM 709 computer

    CERN Document Server

    CERN PhotoLab


    CERN's first computer, a huge vacuum-tube Ferranti Mercury, was installed in building 2 in 1958. With its 60 microsecond clock cycle, it was a million times slower than today's big computers. The Mercury took 3 months to install and filled a huge room, even so, its computational ability didn't quite match that of a modern pocket calculator. "Mass" storage was provided by four magnetic drums each holding 32K x 20 bits - not enough to hold the data from a single proton-proton collision in the LHC. It was replaced in 1960 by the IBM 709 computer, seen here being unloaded at Cointrin airport. Although it was taken over so quickly by transistor equipped machines, a small part of the Ferranti Mercury remains. The computer's engineers installed a warning bell to signal computing errors - it can still be found mounted on the wall in a corridor of building 2.

  14. Baroreceptor unloading does not limit forearm sweat rate during severe passive heat stress. (United States)

    Schlader, Zachary J; Gagnon, Daniel; Lucas, Rebekah A I; Pearson, James; Crandall, Craig G


    This study tested the hypothesis that sweat rate during passive heat stress is limited by baroreceptor unloading associated with heat stress. Two protocols were performed in which healthy subjects underwent passive heat stress that elicited an increase in intestinal temperature of ∼1.8°C. Upon attaining this level of hyperthermia, in protocol 1 (n = 10, 3 females) a bolus (19 ml/kg) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to elevate central venous pressure (CVP), while in protocol 2 (n = 11, 5 females) phenylephrine was infused intravenously (60-120 μg/min) to return mean arterial pressure (MAP) to normothermic levels. In protocol 1, heat stress reduced CVP from 3.9 ± 1.9 mmHg (normothermia) to -0.6 ± 1.4 mmHg (P 0.999). Sweat rate was elevated by heat stress (1.21 ± 0.44 mg·cm(-2)·min(-1)) but remained unchanged during rapid saline infusion (1.26 ± 0.47 mg·cm(-2)·min(-1), P = 0.5), whereas cutaneous vascular conductance increased from 77 ± 10 to 101 ± 20% of local heating max (P = 0.029). In protocol 2, MAP was reduced with heat stress from 85 ± 7 mmHg to 76 ± 8 mmHg (P = 0.048). Although phenylephrine infusion returned MAP to normothermic levels (88 ± 7 mmHg; P > 0.999), sweat rate remained unchanged during phenylephrine infusion (1.39 ± 0.22 vs. 1.41 ± 0.24 mg·cm(-2)·min(-1); P > 0.999). These data indicate that both cardiopulmonary and arterial baroreceptor unloading do not limit increases in sweat rate during passive heat stress. Copyright © 2015 the American Physiological Society.

  15. Evidence of Glycolysis Up-Regulation and Pyruvate Mitochondrial Oxidation Mismatch During Mechanical Unloading of the Failing Human Heart

    Directory of Open Access Journals (Sweden)

    Nikolaos A. Diakos, MD, PhD


    Full Text Available This study sought to investigate the effects of mechanical unloading on myocardial energetics and the metabolic perturbation of heart failure (HF in an effort to identify potential new therapeutic targets that could enhance the unloading-induced cardiac recovery. The authors prospectively examined paired human myocardial tissue procured from 31 advanced HF patients at left ventricular assist device (LVAD implant and at heart transplant plus tissue from 11 normal donors. They identified increased post-LVAD glycolytic metabolites without a coordinate increase in early, tricarboxylic acid (TCA cycle intermediates. The increased pyruvate was not directed toward the mitochondria and the TCA cycle for complete oxidation, but instead, was mainly converted to cytosolic lactate. Increased nucleotide concentrations were present, potentially indicating increased flux through the pentose phosphate pathway. Evaluation of mitochondrial function and structure revealed a lack of post-LVAD improvement in mitochondrial oxidative functional capacity, mitochondrial volume density, and deoxyribonucleic acid content. Finally, post-LVAD unloading, amino acid levels were found to be increased and could represent a compensatory mechanism and an alternative energy source that could fuel the TCA cycle by anaplerosis. In summary, the authors report evidence that LVAD unloading induces glycolysis in concert with pyruvate mitochondrial oxidation mismatch, most likely as a result of persistent mitochondrial dysfunction. These findings suggest that interventions known to improve mitochondrial biogenesis, structure, and function, such as controlled cardiac reloading and conditioning, warrant further investigation to enhance unloading-induced reverse remodeling and cardiac recovery.

  16. MESSENGER Observations of Extreme Loading and Unloading of Mercury's Magnetic Tail (United States)

    Slavin, James A.; Anderson, Brian J.; Baker, Daniel N.; Benna, Mehdi; Boardsen, Scott A.; Gloeckler, George; Gold, Robert E.; Ho, George C.; Korth, Haje; Krimigis, Stamatios M.; hide


    During MESSENGER's third flyby of Mercury, the magnetic field in the planet's magnetotail increased by factors of 2 to 3.5 over intervals of 2 to 3 min. Magnetospheric substorms at Earth are powered by similar tail loading, but the amplitude is approx.10 times less and typical durations are approx.1 hour. The extreme tail loading observed at Mercury implies that the relative intensity of sub storms must be much larger than at Earth. The correspondence between the duration of tail field enhancements and the characteristic time for the Dungey cycle, which describes plasma circulation through Mercury's magnetosphere. suggests that such circulation determines substorm timescale. A key aspect of tail unloading during terrestrial substorms is the acceleration of energetic charged particles, but no acceleration signatures were seen during the MESSENGER flyby.

  17. Loaded and unloaded jump performance of top-level volleyball players from different age categories. (United States)

    Kitamura, Katia; Pereira, Lucas Adriano; Kobal, Ronaldo; Cal Abad, Cesar Cavinato; Finotti, Ronaldo; Nakamura, Fábio Yuzo; Loturco, Irineu


    The aim of this study was to investigate the differences in loaded and unloaded jump performances between different age categories of top-level volleyball players from the same club. Forty-three volleyball players were divided into four age groups: under-17, under-19, under-21 and professional. Vertical jumping height for squat jump (SJ), countermovement jump (CMJ) and CMJ with arm swing (CMJa) and mean propulsive velocity (MPV) in the loaded jump squat exercise with 40% of the athlete's body mass were compared among the different age categories, considering body mass as a covariate. SJ and CMJ jump height values were higher for professional and under-21 players than under-17 players (pvolleyball players. Therefore, to increase the vertical jumping ability of these team sport athletes throughout their long-term development, coaches and strength and conditioning professionals are encouraged to implement consistent neuromuscular training strategies, in accordance with the specific needs and physiological characteristics of each age group.

  18. Mechanical properties of the hindlimb bones of bullfrogs and cane toads in bending and torsion. (United States)

    Wilson, Megan P; Espinoza, Nora R; Shah, Sagar R; Blob, Richard W


    When compared with most vertebrates, frogs use a novel style of jumping locomotion powered by the hindlimbs. Hindlimb bones of frogs must withstand the potentially erratic loads associated with such saltatory locomotion. To evaluate the load bearing capacity of anuran limb bones, we used three-point bending, torsion, and hardness tests to measure the mechanical properties of the femur and tibiofibula from adults of two species that use different jumping styles: explosively jumping bullfrogs (Rana (Lithobates) catesbeiana) and cyclically hopping cane toads (Bufo (Chaunus) marinus). Yield stress and strain values for R. catesbeiana and B. marinus hindlimb bones are within the range of values previously reported for other vertebrates. However, anuran hindlimb bones generally stand out as having higher yield stresses in bending than those of closely related, nonsaltatory salamanders, highlighting the importance of considering phylogenetic context in comparisons of bone functional capacity and adaptation. Stiffness values for both frog species tested were also high, which may facilitate efficient transmission of muscular forces while jumping. Elevated stiffness may also contribute to some discrepancies between determinations of bone properties via hardness versus bending tests. In comparisons between species, B. marinus bones showed significantly higher bending yield stresses than R. catesbeiana, whereas R. catesbeiana bones showed significantly higher torsional yield stresses than B. marinus. These differences may correlate with differences in jumping style and limb anatomy between ranid and bufonid frogs, suggesting that evolutionary changes in bone mechanical properties may help to accommodate new functional demands that emerge in lineages.

  19. Decoding hindlimb movement for a brain machine interface after a complete spinal transection.

    Directory of Open Access Journals (Sweden)

    Anitha Manohar

    Full Text Available Stereotypical locomotor movements can be made without input from the brain after a complete spinal transection. However, the restoration of functional gait requires descending modulation of spinal circuits to independently control the movement of each limb. To evaluate whether a brain-machine interface (BMI could be used to regain conscious control over the hindlimb, rats were trained to press a pedal and the encoding of hindlimb movement was assessed using a BMI paradigm. Off-line, information encoded by neurons in the hindlimb sensorimotor cortex was assessed. Next neural population functions, or weighted representations of the neuronal activity, were used to replace the hindlimb movement as a trigger for reward in real-time (on-line decoding in three conditions: while the animal could still press the pedal, after the pedal was removed and after a complete spinal transection. A novel representation of the motor program was learned when the animals used neural control to achieve water reward (e.g. more information was conveyed faster. After complete spinal transection, the ability of these neurons to convey information was reduced by more than 40%. However, this BMI representation was relearned over time despite a persistent reduction in the neuronal firing rate during the task. Therefore, neural control is a general feature of the motor cortex, not restricted to forelimb movements, and can be regained after spinal injury.

  20. Quantification of fibre type regionalisation : an analysis of lower hindlimb muscles in the rat

    NARCIS (Netherlands)

    Wang, LC; Kernell, D

    Newly developed concepts and methods for the quantification of fibre type regionalisation were used for comparison between all muscles traversing the ankle of the rat lower hindlimb (n = 13). For each muscle, cross-sections from the proximodistal midlevel were stained for myofibrillar ATPase and

  1. Modulation of collateral artery growth in a porcine hindlimb ligation model using MCP-1

    NARCIS (Netherlands)

    Voskuil, Michiel; van Royen, Niels; Hoefer, Imo E.; Seidler, Randolph; Guth, Brian D.; Bode, Christoph; Schaper, Wolfgang; Piek, Jan J.; Buschmann, Ivo R.


    For an appropriate extrapolation to patients with peripheral arterial obstructive disease, we tested the efficacy of monocyte chemoattractant protein 1 (MCP-1) treatment in a porcine hindlimb ligation model. In 40 minipigs, a femoral artery ligation was performed. Control animals were examined

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

    Directory of Open Access Journals (Sweden)

    Monzurul Alam

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

  3. Decoding hindlimb movement for a brain machine interface after a complete spinal transection. (United States)

    Manohar, Anitha; Flint, Robert D; Knudsen, Eric; Moxon, Karen A


    Stereotypical locomotor movements can be made without input from the brain after a complete spinal transection. However, the restoration of functional gait requires descending modulation of spinal circuits to independently control the movement of each limb. To evaluate whether a brain-machine interface (BMI) could be used to regain conscious control over the hindlimb, rats were trained to press a pedal and the encoding of hindlimb movement was assessed using a BMI paradigm. Off-line, information encoded by neurons in the hindlimb sensorimotor cortex was assessed. Next neural population functions, or weighted representations of the neuronal activity, were used to replace the hindlimb movement as a trigger for reward in real-time (on-line decoding) in three conditions: while the animal could still press the pedal, after the pedal was removed and after a complete spinal transection. A novel representation of the motor program was learned when the animals used neural control to achieve water reward (e.g. more information was conveyed faster). After complete spinal transection, the ability of these neurons to convey information was reduced by more than 40%. However, this BMI representation was relearned over time despite a persistent reduction in the neuronal firing rate during the task. Therefore, neural control is a general feature of the motor cortex, not restricted to forelimb movements, and can be regained after spinal injury.

  4. A brain-machine-muscle interface for restoring hindlimb locomotion after complete spinal transection in rats. (United States)

    Alam, Monzurul; Chen, Xi; Zhang, Zicong; Li, Yan; He, Jufang


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

  5. Regional distribution of slow-twitch muscle fibers after reinnervation in adult rat hindlimb muscles

    NARCIS (Netherlands)

    Wang, LC; Copray, S; Brouwer, N; Meek, MF; Kernell, D

    the knee. Following a survival time of 21 weeks, five muscles were removed from both lower hindlimbs after determining their intra-limb positions. In each muscle, cryostat sections from seven equidistant proximo-distal levels were stained for myofibrillar ATPase. Intramuscular positions were

  6. Impact of combined clenbuterol and metoprolol therapy on reverse remodelling during mechanical unloading.

    Directory of Open Access Journals (Sweden)

    Manoraj Navaratnarajah

    Full Text Available Clenbuterol (Cl, a β2 agonist, is associated with enhanced myocardial recovery during left ventricular assist device (LVAD support, and exerts beneficial remodelling effects during mechanical unloading (MU in rodent heart failure (HF. However, the specific effects of combined Cl+β1 blockade during MU are unknown.We studied the chronic effects (4 weeks of β2-adrenoceptor (AR stimulation via Cl (2 mg/kg/day alone, and in combination with β1-AR blockade using metoprolol ((Met, 250 mg/kg/day, on whole heart/cell structure, function and excitation-contraction (EC coupling in failing (induced by left coronary artery (LCA ligation, and unloaded (induced by heterotopic abdominal heart transplantation (HATx failing rat hearts. Combined Cl+Met therapy displayed favourable effects in HF: Met enhanced Cl's improvement in ejection fraction (EF whilst preventing Cl-induced hypertrophy and tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MU-induced myocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+ transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Met mono-therapy, but these benefits, together with Cl's enhancement of sarcomeric contraction speed, and MU-induced recovery of Ca2+ spark frequency, disappeared during combined therapy.Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appears inferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined β2-AR simulation +β1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective as mono-therapy in enhancing myocardial recovery during LVAD support.

  7. Importance of loading and unloading procedures for gecko-inspired controllable adhesives. (United States)

    Tamelier, John; Chary, Sathya; Turner, Kimberly L


    The importance of loading and unloading procedures has been shown in a variety of different methods for biological dry adhesives, such as the fibers on the feet of the Tokay gecko, but biomimetic dry adhesives have yet to be explored in a similar manner. To date, little work has systematically varied multiple parameters to discern the influence of the testing procedure, and the effect of the approach angle remains uncertain. In this study, a synthetic adhesive is moved in 13 individual approach and retraction angles relative to a flat substrate as well as 9 different shear lengths to discern how loading and unloading procedures influence the preload, adhesion, and shear/friction forces supported. The synthetic adhesive, composed of vertical 10 μm diameter semicircular poly(dimethylsiloxane) fibers, is tested against a 4 mm diameter flat glass puck on a home-built microtribometer using both vertical approach and retraction tests and angled approach and retraction tests. The results show that near maximum adhesion and friction can be obtained for most approach and retraction angles, provided that a sufficient shear length is performed. The results also show that the reaction forces during adhesive placement can be significantly reduced by using specific approach angles, resulting for the vertical fibers in a 38-fold increase in the ratio of adhesion force to preload force, μ', when compared to that when using a vertical approach. These results can be of use to those currently researching gecko-inspired adhesives when designing their testing procedures and control algorithms for climbing and perching robots.

  8. Biomechanical effect of unloader braces for medial osteoarthritis of the knee: a systematic review (CRD 42015026136). (United States)

    Petersen, Wolf; Ellermann, Andree; Zantop, Thore; Rembitzki, Ingo Volker; Semsch, Hartmut; Liebau, Christian; Best, Raymond


    There is a lack of consensus regarding biomechanical effects of unloader braces for the treatment of medial osteoarthritis (OA) of the knee. The purpose of this study was to perform a systematic review of studies examining the biomechanical effect of unloader braces. A systematic search for articles about the biomechanical effect of unloader braces was performed. Primary outcome measure was the influence of the brace on the knee adduction moment. Data sources were Pubmed central and google scholar. Twenty-four articles were included. Twenty articles showed that valgus unloader braces significantly decrease the knee adduction moment. Seven of those studies reported a decrease of pain in braced patients (secondary outcome measure). Positive effects on the knee adduction moment could be found for custom made braces for conventional knee braces and for a foot ankle orthosis. Four studies could not show any effect of knee unloader braces on the knee adduction moment although one of these studies found decreased pain in braced patients. One of these studies examined healthy patients with a neutral axis. This systematic review could demonstrate evidence that unloader braces reduce the adduction moment of the knee. Foresighted, a systematic review about the clinical effect of unloader braces is required.

  9. Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure. (United States)

    Borghi-Silva, Audrey; Carrascosa, Cláudia; Oliveira, Cristino Carneiro; Barroco, Adriano C; Berton, Danilo C; Vilaça, Debora; Lira-Filho, Edgar B; Ribeiro, Dirceu; Nery, Luiz Eduardo; Neder, J Alberto


    Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 +/- 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation (P 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Delta[O2Hb]% and Delta[HbTOT]%, respectively (P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.

  10. Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats (United States)

    Tou, Janet C L.; Grindeland, Richard E.; Wade, Charles E.


    Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

  11. Experimental evidence of the tonic vibration reflex during whole-body vibration of the loaded and unloaded leg.

    Directory of Open Access Journals (Sweden)

    Lisa N Zaidell

    Full Text Available Increased muscle activation during whole-body vibration (WBV is mainly ascribed to a complex spinal and supraspinal neurophysiological mechanism termed the tonic vibration reflex (TVR. However, TVR has not been experimentally demonstrated during low-frequency WBV, therefore this investigation aimed to determine the expression of TVR during WBV. Whilst seated, eight healthy males were exposed to either vertical WBV applied to the leg via the plantar-surface of the foot, or Achilles tendon vibration (ATV at 25 Hz and 50 Hz for 70s. Ankle plantar-flexion force, tri-axial accelerations at the shank and vibration source, and surface EMG activity of m. soleus (SOL and m. tibialis anterior (TA were recorded from the unloaded and passively loaded leg to simulate body mass supported during standing. Plantar flexion force was similarly augmented by WBV and ATV and increased over time in a load- and frequency dependent fashion. SOL and TA EMG amplitudes increased over time in all conditions independently of vibration mode. 50 Hz WBV and ATV resulted in greater muscle activation than 25 Hz in SOL when the shank was loaded and in TA when the shank was unloaded despite the greater transmission of vertical acceleration from source to shank with 25 Hz and WBV, especially during loading. Low-amplitude WBV of the unloaded and passively loaded leg produced slow tonic muscle contraction and plantar-flexion force increase of similar magnitudes to those induced by Achilles tendon vibration at the same frequencies. This study provides the first experimental evidence supporting the TVR as a plausible mechanism underlying the neuromuscular response to whole-body vibration.

  12. Musculoskeletal Geometry, Muscle Architecture and Functional Specialisations of the Mouse Hindlimb.

    Directory of Open Access Journals (Sweden)

    James P Charles

    Full Text Available Mice are one of the most commonly used laboratory animals, with an extensive array of disease models in existence, including for many neuromuscular diseases. The hindlimb is of particular interest due to several close muscle analogues/homologues to humans and other species. A detailed anatomical study describing the adult morphology is lacking, however. This study describes in detail the musculoskeletal geometry and skeletal muscle architecture of the mouse hindlimb and pelvis, determining the extent to which the muscles are adapted for their function, as inferred from their architecture. Using I2KI enhanced microCT scanning and digital segmentation, it was possible to identify 39 distinct muscles of the hindlimb and pelvis belonging to nine functional groups. The architecture of each of these muscles was determined through microdissections, revealing strong architectural specialisations between the functional groups. The hip extensors and hip adductors showed significantly stronger adaptations towards high contraction velocities and joint control relative to the distal functional groups, which exhibited larger physiological cross sectional areas and longer tendons, adaptations for high force output and elastic energy savings. These results suggest that a proximo-distal gradient in muscle architecture exists in the mouse hindlimb. Such a gradient has been purported to function in aiding locomotor stability and efficiency. The data presented here will be especially valuable to any research with a focus on the architecture or gross anatomy of the mouse hindlimb and pelvis musculature, but also of use to anyone interested in the functional significance of muscle design in relation to quadrupedal locomotion.

  13. Hindlimb motion during steady flight of the lesser dog-faced fruit bat, Cynopterus brachyotis.

    Directory of Open Access Journals (Sweden)

    Jorn A Cheney

    Full Text Available In bats, the wing membrane is anchored not only to the body and forelimb, but also to the hindlimb. This attachment configuration gives bats the potential to modulate wing shape by moving the hindlimb, such as by joint movement at the hip or knee. Such movements could modulate lift, drag, or the pitching moment. In this study we address: 1 how the ankle translates through space during the wingbeat cycle; 2 whether amplitude of ankle motion is dependent upon flight speed; 3 how tension in the wing membrane pulls the ankle; and 4 whether wing membrane tension is responsible for driving ankle motion. We flew five individuals of the lesser dog-faced fruit bat, Cynopterus brachyotis (Family: Pteropodidae, in a wind tunnel and documented kinematics of the forelimb, hip, ankle, and trailing edge of the wing membrane. Based on kinematic analysis of hindlimb and forelimb movements, we found that: 1 during downstroke, the ankle moved ventrally and during upstroke the ankle moved dorsally; 2 there was considerable variation in amplitude of ankle motion, but amplitude did not correlate significantly with flight speed; 3 during downstroke, tension generated by the wing membrane acted to pull the ankle dorsally, and during upstroke, the wing membrane pulled laterally when taut and dorsally when relatively slack; and 4 wing membrane tension generally opposed dorsoventral ankle motion. We conclude that during forward flight in C. brachyotis, wing membrane tension does not power hindlimb motion; instead, we propose that hindlimb movements arise from muscle activity and/or inertial effects.

  14. Choroidal responses in microgravity. (SLS-1, SLS-2 and hindlimb-suspension experiments) (United States)

    Gabrion, J.; Herbuté, S.; Oliver, J.; Maurel, D.; Davet, J.; Clavel, B.; Gharib, C.; Fareh, J.; Fagette, S.; Nguyen, B.

    Fluid and electrolyte shifts occuring during human spaceflight have been reported and investigated at the level of blood, cardio-vascular and renal responses. Very few data were available concerning the cerebral fluid and electrolyte adaptation to microgravity, even in animal models. It is the reason why we developed several studies focused on the effects of spaceflight (SLS-1 and SLS-2 programs, carried on NASA STS 40 and 56 missions, which were 9- and 14-day flights, respectively), on structural and functional features of choroid plexuses, organs which secrete 70-90 % of cerebrospinal fluid (CSF) and which are involved in brain homeostasis. Rats flown aboard space shuttles were sacrificed either in space (SLS-2 experiment, on flight day 13) or 4-8 hours after landing (SLS-1 and SLS-2 experiments). Quantitative autoradiography performed by microdensitometry and image analysis, showed that lateral and third ventricle choroid plexuses from rats flown for SLS-1 experiment demonstrated an increased number (about x 2) of binding sites to natriuretic peptides (which are known to be involved in mechanisms regulating CSF production). Using electron microscopy and immunocytochemistry, we studied the cellular response of choroid plexuses, which produce cerebrospinal fluid (CSF) in brain lateral, third and fourth ventricles. We demonstrated that spaceflight (SLS-2 experiment, inflight samples) induces changes in the choroidal cell structure (apical microvilli, kinocilia organization, vesicle accumulation) and protein distribution or expression (carbonic anhydrase II, water channels,…). These observations suggested a loss of choroidal cell polarity and a decrease in CSF secretion. Hindlimb-suspended rats displayed similar choroidal changes. All together, these results support the hypothesis of a modified CSF production in rats during long-term (9, 13 or 14 days) adaptations to microgravity.

  15. Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia. (United States)

    Francki, Aleksandar; Labazzo, Kristen; He, Shuyang; Baum, Ellen Z; Abbot, Stewart E; Herzberg, Uri; Hofgartner, Wolfgang; Hariri, Robert


    Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population from full-term placental tissue and were previously shown to possess anti-inflammatory and immunomodulatory properties. PDACs (formulated as PDA-002) are in clinical trials for peripheral arterial disease with diabetic foot ulcer. In the current study, we examined their angiogenic and tissue reparative properties. The effects of PDACs on survival and tube formation of human umbilical vein endothelial cells (HUVECs) were tested using conditioned media and noncontact coculture. Angiogenic effects were assessed in the chick chorioallantoic membrane assay. Hindlimb ischemia (HLI) was induced in mice and rats by femoral artery transection, and blood flow and blood vessel density were monitored in vivo by laser Doppler and angiography in the ischemic and control limbs. Tissue damage and regeneration in HLI were examined in histologic sections of quadriceps muscle stained with hematoxylin and eosin, and newly synthesized blood vessels were detected by indoxyl-tetrazolium staining for alkaline phosphatase. PDACs enhanced the survival of serum-starved HUVECs and stimulated HUVEC tube formation, and in the chick chorioallantoic membrane assay, PDACs stimulated blood vessel formation. In HLI, intramuscular administration of PDACs resulted in improved blood flow and vascular density, and in quadriceps muscle, tissue regeneration and increased numbers of blood vessels were observed. PDACs exhibited various activities consistent with angiogenesis and tissue repair, supporting the continued investigation of this cell therapy as treatment for vascular disease-related indications. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  16. [Hindlimb antigravity muscles' reaction in male and female rats to the deficit of functional loading]. (United States)

    Il'ina-Kakueva, E I


    Histological and histomorphometric comparison of the antigravity muscles of rats of both sexes was performed following 30-d unloading of their hind limbs by head-down suspension. It was shown that growth rate of control males was higher as compared to control females. This is attributed to the synergic effects of somatotropin and testosterone on metabolism and growth of males and only somatotropin in females. Load deprivation of the hind limbs inhibited body mass gain in all animals; however, this inhibition was twice as great in males. Increase of the soleus and gastrocnemius in the control males in this experiment was slightly ahead of the muscle mass gain in the females. The histomorphometric investigation of the cross-section area of myofibers did not reveal differences between males and females either in the control or suspension. No difference was found in percent of various types of fibers in the control males and females. In the soleus of the suspended rats, a part of slow fibers had transformed into fast ones without any sex-related particularities. The conclusion was made that despite the significant difference in the hormonal profile, the reaction of males and females to insufficient weight loading of the antigravity muscles was alike.

  17. Identification of genes associated with regenerative success of Xenopus laevis hindlimbs

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    Barker Donna


    Full Text Available Abstract Background Epimorphic regeneration is the process by which complete regeneration of a complex structure such as a limb occurs through production of a proliferating blastema. This type of regeneration is rare among vertebrates but does occur in the African clawed frog Xenopus laevis, traditionally a model organism for the study of early development. Xenopus tadpoles can regenerate their tails, limb buds and the lens of the eye, although the ability of the latter two organs to regenerate diminishes with advancing developmental stage. Using a heat shock inducible transgene that remains silent unless activated, we have established a stable line of transgenic Xenopus (strain N1 in which the BMP inhibitor Noggin can be over-expressed at any time during development. Activation of this transgene blocks regeneration of the tail and limb of Xenopus tadpoles. Results In the current study, we have taken advantage of the N1 transgenic line to directly compare morphology and gene expression in same stage regenerating vs. BMP signalling deficient non-regenerating hindlimb buds. The wound epithelium of N1 transgenic hindlimb buds, which forms over the cut surface of the limb bud after amputation, does not transition normally into the distal thickened apical epithelial cap. Instead, a basement membrane and dermis form, indicative of mature skin. Furthermore, the underlying mesenchyme remains rounded and does not expand to form a cone shaped blastema, a normal feature of successful regeneration. Using Affymetrix Gene Chip analysis, we have identified genes linked to regenerative success downstream of BMP signalling, including the BMP inhibitor Gremlin and the stress protein Hsp60 (no blastema in zebrafish. Gene Ontology analysis showed that genes involved in embryonic development and growth are significantly over-represented in regenerating early hindlimb buds and that successful regeneration in the Xenopus hindlimb correlates with the induction of

  18. Nandrolone decanoate reduces changes induced by hindlimb suspension in voltage-dependent tension of rat soleus muscle. (United States)

    Bouhlel, Aicha; Joumaa, Wissam H; Léoty, Claude


    The effect of 8 weeks of nandrolone decanoate treatment (15 mg kg(-1)/week, 5 weeks under normal conditions followed by 3 weeks of unloading) was tested for the voltage-dependence of activation and steady-state inactivation of contraction in isolated small bundles (2-4 cells) of intact slow-twitch skeletal muscle in rats. Twenty-four male rats were divided into three groups (8 rats/group, weight matched) for 8 weeks: (1) control, (2) unloaded, and (3) unloaded-treated. Compared with age-matched control values (unloaded vs. control), suspension induced a shift in the isometric tension characteristics toward fast-twitch types in the soleus muscle. In contrast, nandrolone decanoate treatment of suspended animals reduced unweighting-induced atrophy in the muscle and maintained: (1) the relative amplitude of twitch tension to the maximal Ca(2+) activated in saponin-treated fibers (control: 3.6 +/- 0.4%, unloaded: 6.9 +/- 1.1% and unloaded-treated: 4.6 +/- 0.2%), (2) the time to peak tension (control: 130 +/- 18 ms, unloaded: 85 +/- 12 ms and unloaded-treated: 110 +/- 11 ms), (3) the time constant of relaxation (control: 320 +/- 12 ms, unloaded: 120 +/- 13 ms and unloaded-treated: 349 +/- 20 ms), (4) the relative amplitude of K(+) contracture tension to the maximal Ca(2+) activated in saponin-treated fibers (control: 82.9 +/- 3.1%, unloaded: 65.1 +/- 2.8%, and unloaded-treated: 91.7 +/- 1.9%), (5) the potential at 50% of the activation curve (control: -40.4 +/- 1.2 mV, unloaded: -35.5 +/- 1.6 mV, and unloaded-treated: -48.4 +/- 1.2 mV), and (6) the potential at 50% of the inactivation curve (control: 42.2 +/- 1.9 mV, unloaded: -34.5 +/- 1.1 mV, and unloaded-treated: -37.9 +/- 1.1 mV). This study clearly shows that treatment with anabolic-androgenic steroids can prevent atrophy and functional changes induced by 3 weeks of unweighting in rat skeletal muscles.

  19. Identifying optimal parameters for quantification of changes in pelvic movement symmetry as a response to diagnostic analgesia in the hindlimbs of horses. (United States)

    Pfau, T; Spicer-Jenkins, C; Smith, R K; Bolt, D M; Fiske-Jackson, A; Witte, T H


    Subjective evaluation of the response to diagnostic analgesia of hindlimb lameness is influenced by expectation bias. Quantification of pelvic movement with inertial measurement units is possible, but it is unclear which measure of movement symmetry best reflects the changes seen after diagnostic analgesia. To test our hypothesis that objective measures closely relating to those used for subjective visual lameness scoring (quantifying the difference between sacral upward or downward movement or between movement amplitudes of the left and right tubera coxae) would show the largest and most consistent response. Retrospective analysis of subjective and objective clinical lameness data. Thirteen horses with hindlimb lameness underwent visual lameness scoring and independent gait assessment with inertial measurement units. Established objective measures were calculated and changes before/after diagnostic analgesia regressed against the change in lameness grade. Slopes of regression lines were calculated and confidence intervals assessed. All objective parameters showed variation between horses and across lameness grades. The following 3 measures documented a consistent increase in symmetry for each grade of change in lameness score: difference between sacral displacement minima; upward movement difference; and range of motion difference between the tubera coxae. Several pelvic parameters are suitable for objective quantification of changes after diagnostic analgesia in hindlimb-lame horses. A change of 9-13% per lameness grade can be expected. Upward movement of the tubera coxae is the most sensitive objective measure for quantifying a response to diagnostic analgesia. However, when assessed visually, this measure requires simultaneous focusing on pelvic and limb movements. Other parameters that show a similar response might be more easily perceived, requiring only assessment of tubera coxae range of motion or downward displacement of the sacrum without simultaneous

  20. Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure. (United States)

    Soppa, Gopal K R; Lee, Joon; Stagg, Mark A; Felkin, Leanne E; Barton, Paul J R; Siedlecka, Urszula; Youssef, Samuel; Yacoub, Magdi H; Terracciano, Cesare M N


    Combined left ventricular assist device (LVAD) and pharmacological therapy has been proposed to favour myocardial recovery in patients with end-stage heart failure (HF). Clenbuterol (Clen), a beta(2)-adrenoceptor (beta(2)-AR) agonist, has been used as a part of this strategy. In this study, we investigated the direct effects of clenbuterol on unloaded myocardium in HF. Left coronary artery ligation or sham operation was performed in male Lewis rats. After 4-6 weeks, heterotopic abdominal transplantation of the failing hearts into normal recipients was performed to induce LV unloading (UN). Recipient rats were treated with saline (Sal) or clenbuterol (2 mg/kg/day) via osmotic minipumps (HF + UN + Sal or HF + UN + Clen) for 7 days. Non-transplanted HF animals were treated with Sal (Sham + Sal, HF + Sal) or clenbuterol (HF + Clen). LV myocytes were isolated and studied using optical, fluorescence, and electrophysiological techniques. Clenbuterol treatment improved in vivo LV function measured with echocardiography (LVEF (%): HF 35.9 +/- 2 [16], HF + Clen 52.1 +/- 1.4 [16]; P clenbuterol increased sarcomere shortening (amplitude (microm): HF + UN + Clen 0.1 +/- 0.01 [50], HF + UN + Sal 0.07 +/- 0.01 [38]; P Clenbuterol treatment of failing rat hearts, alone or in combination with mechanical unloading, improves LV function at the whole-heart and cellular levels by affecting cell morphology, excitation-contraction coupling, and myofilament sensitivity to calcium. This study supports the use of this drug in the strategy to enhance recovery in HF patients treated with LVADs and also begins to elucidate some of the possible cellular mechanisms responsible for the improvement in LV function.

  1. Energy Evolution Characteristics and Distribution Laws of Rock Materials under Triaxial Cyclic Loading and Unloading Compression

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    Mingwei Zhang


    Full Text Available To explore the influence of confining pressure on the energy evolution characteristics of loaded rocks, triaxial cyclic loading-unloading experiments on sandstones were carried out under 6 kinds of confining pressures using the axial loading and circumferential deforming control modes. Total energy density, elastic energy density, and dissipated energy density absorbed by rock specimens under different confining pressures were obtained. The confining pressure effect of the evolution process and distribution law in energy accumulation and dissipation was analyzed. Energy conversion mechanism from rock deformation to failure was revealed, and energy conversion equations in different stress-strain stages were established. The method of representing the rock energy accumulation, dissipation, and release behaviors by energy storage limit density, maximum dissipated energy density, and residual elastic energy density was established. The rock showed that, with the increase of confining pressure, the characteristic energy density of rock increased in the power exponent form, and the energy storage limit density increased faster than the maximum dissipated energy density. The greater the confining pressure was, the greater the proportion of elastic energy before peak was. It is indicated that the confining pressure increased the energy inputting intensity, improved the energy accumulating efficiency, and inhibited the energy releasing degree.

  2. Acute effects of hindlimb unweighting on satellite cells of growing skeletal muscle (United States)

    Schultz, Edward; Darr, Kevin C.; Macius, Allison


    The proliferative behavior of satellite cells in growing rat soleus and extensor digitorum longus muscles was examined at short periods after initiation of hindlimb unweighting. Mitotic activity of satellite cells in both muscles decreased below weight-bearing control levels within 24 h of initiation of hindlimb unweighting. This satellite cell response was equal to or greater than 48 h before any atrophic morphological changes that take place in the muscles. Suppression of mitotic activity was most severe in the soleus muscle where continuous infusion of label demonstrated that virtually all mitotic activity was abolished between 3 and 5 days. The results of this study suggest that satellite cell mitotic activity is a sensitive indicator of primary atrophic changes occurring in growing myofibers and may be a predictor of future morphological changes.

  3. Influence of Androgen Receptor in Vascular Cells on Reperfusion following Hindlimb Ischaemia.

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    Junxi Wu

    Full Text Available Studies in global androgen receptor knockout (G-ARKO and orchidectomised mice suggest that androgen accelerates reperfusion of the ischaemic hindlimb by stimulating angiogenesis. This investigation used novel, vascular cell-specific ARKO mice to address the hypothesis that the impaired hindlimb reperfusion in G-ARKO mice was due to loss of AR from cells in the vascular wall.Mice with selective deletion of AR (ARKO from vascular smooth muscle cells (SM-ARKO, endothelial cells (VE-ARKO, or both (SM/VE-ARKO were compared with wild type (WT controls. Hindlimb ischaemia was induced in these mice by ligation and removal of the femoral artery. Post-operative reperfusion was reduced in SM-ARKO and SM/VE-ARKO mice. Immunohistochemistry indicated that this was accompanied by a reduced density of smooth muscle actin-positive vessels but no change in the density of isolectin B4-positive vessels in the gastrocnemius muscle. Deletion of AR from the endothelium (VE-ARKO did not alter post-operative reperfusion or vessel density. In an ex vivo (aortic ring culture model of angiogenesis, AR was not detected in vascular outgrowths and angiogenesis was not altered by vascular ARKO or by exposure to dihydrotestosterone (DHT 10-10-10-7M; 6 days.These results suggest that loss of AR from vascular smooth muscle, but not from the endothelium, contributes to impaired reperfusion in the ischaemic hindlimb of G-ARKO. Impaired reperfusion was associated with reduced collateral formation rather than reduced angiogenesis.

  4. Heterogenic Feedback Between Hindlimb Extensors in the Spontaneously Locomoting Premammillary Cat


    Ross, Kyla T.; Nichols, T. Richard


    Electrophysiological studies in anesthetized animals have revealed that pathways carrying force information from Golgi tendon organs in antigravity muscles mediate widespread inhibition among other antigravity muscles in the feline hindlimb. More recent evidence in paralyzed or nonparalyzed decerebrate cats has shown that some inhibitory pathways are suppressed and separate excitatory pathways from Golgi tendon organ afferents are opened on the transition from steady force production to locom...

  5. Tie2-dependent neovascularization of the ischemic hindlimb is mediated by angiopoietin-2.

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    Michael Lekas

    Full Text Available The angiopoietins (ANGPT are ligands for the endothelial cell (EC receptor tyrosine kinase, Tie2. Angpt-1 is a Tie2 agonist that promotes vascular maturation and stabilization, whereas Angpt-2 is a partial agonist/antagonist involved in the initiation of postnatal angiogenesis. Therefore, we hypothesized that overexpression of Angpt-2 would be more effective than Angpt-1 for enhancing the perfusion recovery in the ischemic hindlimb. Perfusion recovery was markedly impaired in Tie2-deficient animals at day 35 in a model of chronic hindlimb ischemia. Injections of Angpt-2 or VEGFA plasmid at 7 days post femoral artery resection enhanced recovery and improved arteriogenesis as assessed by angiographic scores, whereas Angpt-1 or null plasmid had no effect. In addition, Angpt-2 together with VEGF resulted in greater improvement in perfusion and collateral vessel formation than VEGF alone. Similarly, conditional overexpression of Angpt-2 in mice improved ischemic limb blood flow recovery, while Angpt-1 overexpression was ineffective. These data from Tie2 heterozygote deficient mice demonstrate, for the first time, the importance of the Tie2 pathway in spontaneous neovascularization in response to chronic hindlimb ischemia. Moreover, they show that overexpression of the partial agonist, Angpt-2, but not Angpt-1, enhanced ischemic hind limb perfusion recovery and collateralization, suggesting that a coordinated sequence antagonist and agonist activity is required for effective therapeutic revascularization.

  6. Planar Covariation of Hindlimb and Forelimb Elevation Angles during Terrestrial and Aquatic Locomotion of Dogs.

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    Giovanna Catavitello

    Full Text Available The rich repertoire of locomotor behaviors in quadrupedal animals requires flexible inter-limb and inter-segmental coordination. Here we studied the kinematic coordination of different gaits (walk, trot, gallop, and swim of six dogs (Canis lupus familiaris and, in particular, the planar covariation of limb segment elevation angles. The results showed significant variations in the relative duration of rearward limb movement, amplitude of angular motion, and inter-limb coordination, with gait patterns ranging from a lateral sequence of footfalls during walking to a diagonal sequence in swimming. Despite these differences, the planar law of inter-segmental coordination was maintained across different gaits in both forelimbs and hindlimbs. Notably, phase relationships and orientation of the covariation plane were highly limb specific, consistent with the functional differences in their neural control. Factor analysis of published muscle activity data also demonstrated differences in the characteristic timing of basic activation patterns of the forelimbs and hindlimbs. Overall, the results demonstrate that the planar covariation of inter-segmental coordination has emerged for both fore- and hindlimbs and all gaits, although in a limb-specific manner.

  7. Mechanical Behavior and Permeability Evolution of Reconstituted Coal Samples under Various Unloading Confining Pressures—Implications for Wellbore Stability Analysis

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    Qiangui Zhang


    Full Text Available Low pressure, low permeability, and low saturation of Chinese coal-bed methane (CBM reservoirs make underbalanced drilling (UBD widely used for mining CBM in China. In this study, mechanical behavior and permeability of coal rock were investigated under different degrees of unloading confining pressure (UCP-reloading axial stress (RAS by a triaxial experimental apparatus. These tests revealed that: (1 peak deviatoric stress of coal rock in UCP-RAS is lower than that in a conventional triaxial compression (CTC test, and the peak deviatoric stress linearly relates the degree of unloading confining pressure. The deformation modulus of coal in UCP-RAS is lower than that in CTC, while the lateral expansion ratio is larger than that in CTC; (2 higher UCP leads to a faster increase of permeability during RAS until the failure of coal; (3 the cohesion and internal friction angle tested by UCP-RAS are lower by 4.57% and 15.18% than those tested by CTC. In addition, a field case (Zhaozhuang well, Qinshui Basin, China of a well collapse problem validates the higher probability of wellbore collapse due to the increase of equivalent collapse fluid density, which is calculated by using coal rock parameters tested by UCP-RAS rather than by CTC.

  8. Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats (United States)

    Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.


    It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water

  9. Relationship between Deck Level, Body Surface Temperature and Carcass Damages in Italian Heavy Pigs after Short Journeys at Different Unloading Environmental Conditions. (United States)

    Arduini, Agnese; Redaelli, Veronica; Luzi, Fabio; Dall'Olio, Stefania; Pace, Vincenzo; Nanni Costa, Leonardo


    In order to evaluate the relationships between deck level, body surface temperature and carcass damages after a short journey (30 min), 10 deliveries of Italian heavy pigs, including a total of 1400 animals from one farm, were examined. Within 5 min after the arrival at the abattoir, the vehicles were unloaded. Environmental temperature and relative humidity were recorded and a Temperature Humidity Index (THI) was calculated. After unloading, maximum temperatures of dorsal and ocular regions were measured by a thermal camera on groups of pigs from each of the unloaded decks. After dehairing, quarters and whole carcasses were evaluated subjectively by a trained operator for skin damage using a four-point scale. On the basis of THI at unloading, deliveries were grouped into three classes. Data of body surface temperature and skin damage score were analysed in a model including THI class, deck level and their interaction. Regardless of pig location in the truck, the maximum temperature of the dorsal and ocular regions increased with increasing THI class. Within each THI class, the highest and lowest body surface temperatures were found in pigs located on the middle and upper decks, respectively. Only THI class was found to affect the skin damage score (p < 0.05), which increased on quarters and whole carcasses with increasing THI class. The results of this study on short-distance transport of Italian heavy pigs highlighted the need to control and ameliorate the environmental conditions in the trucks, even at relatively low temperature and THI, in order to improve welfare and reduce loss of carcass value.

  10. Relationship between Deck Level, Body Surface Temperature and Carcass Damages in Italian Heavy Pigs after Short Journeys at Different Unloading Environmental Conditions

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    Agnese Arduini


    Full Text Available In order to evaluate the relationships between deck level, body surface temperature and carcass damages after a short journey (30 min, 10 deliveries of Italian heavy pigs, including a total of 1400 animals from one farm, were examined. Within 5 min after the arrival at the abattoir, the vehicles were unloaded. Environmental temperature and relative humidity were recorded and a Temperature Humidity Index (THI was calculated. After unloading, maximum temperatures of dorsal and ocular regions were measured by a thermal camera on groups of pigs from each of the unloaded decks. After dehairing, quarters and whole carcasses were evaluated subjectively by a trained operator for skin damage using a four-point scale. On the basis of THI at unloading, deliveries were grouped into three classes. Data of body surface temperature and skin damage score were analysed in a model including THI class, deck level and their interaction. Regardless of pig location in the truck, the maximum temperature of the dorsal and ocular regions increased with increasing THI class. Within each THI class, the highest and lowest body surface temperatures were found in pigs located on the middle and upper decks, respectively. Only THI class was found to affect the skin damage score (p < 0.05, which increased on quarters and whole carcasses with increasing THI class. The results of this study on short-distance transport of Italian heavy pigs highlighted the need to control and ameliorate the environmental conditions in the trucks, even at relatively low temperature and THI, in order to improve welfare and reduce loss of carcass value.

  11. Aquaporins and unloading of phloem-imported water in coats of developing bean seeds. (United States)

    Zhou, Yuchan; Setz, Nathan; Niemietz, Christa; Qu, Hongxia; Offler, Christina E; Tyerman, Stephen D; Patrick, John W


    Nutrients are imported into developing legume seeds by mass flow through the phloem, and reach developing embryos following secretion from their symplasmically isolated coats. To sustain homeostasis of seed coat water relations, phloem-delivered nutrients and water must exit seed coats at rates commensurate with those of import through the phloem. In this context, coats of developing French bean seeds were screened for expression of aquaporin genes resulting in cloning PvPIP1;1, PvPIP2;2 and PvPIP2;3. These genes were differentially expressed in all vegetative organs, but exhibited their strongest expression in seed coats. In seed coats, expression was localized to cells of the nutrient-unloading pathway. Transport properties of the PvPIPs were characterized by expression in Xenopus oocytes. Only PvPIP2;3 showed significant water channel activity (Pos = 150-200 microm s(-1)) even when the plasma membrane intrinsic proteins (PIPs) were co-expressed in various combinations. Permeability increases to glycerol, methylamine and urea were not detected in oocytes expressing PvPIPs. Transport active aquaporins in native plasma membranes of seed coats were demonstrated by measuring rates of osmotic shrinkage of membrane vesicles in the presence and absence of mercuric chloride and silver nitrate. The functional significance of aquaporins in nutrient and water transport in developing seeds is discussed.

  12. Loaded and unloaded jump performance of top-level volleyball players from different age categories (United States)

    Kitamura, Katia; Pereira, Lucas Adriano; Kobal, Ronaldo; Cal Abad, Cesar Cavinato; Finotti, Ronaldo; Nakamura, Fábio Yuzo


    The aim of this study was to investigate the differences in loaded and unloaded jump performances between different age categories of top-level volleyball players from the same club. Forty-three volleyball players were divided into four age groups: under-17, under-19, under-21 and professional. Vertical jumping height for squat jump (SJ), countermovement jump (CMJ) and CMJ with arm swing (CMJa) and mean propulsive velocity (MPV) in the loaded jump squat exercise with 40% of the athlete’s body mass were compared among the different age categories, considering body mass as a covariate. SJ and CMJ jump height values were higher for professional and under-21 players than under-17 players (pjump squat was higher for under-21 players than under-17 players (pvertical jump performances across different age categories of top-level volleyball players. Therefore, to increase the vertical jumping ability of these team sport athletes throughout their long-term development, coaches and strength and conditioning professionals are encouraged to implement consistent neuromuscular training strategies, in accordance with the specific needs and physiological characteristics of each age group. PMID:29158621

  13. Investigating the effect of unloading on artificial sandstone behaviour using the Discrete Element Method

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    Huang Yueqin


    Full Text Available The Discrete Element Method (DEM was used to simulate the mechanical behaviour of a reservoir sandstone. Triaxial tests were carried out using 3D-DEM to simulate the stress-strain behaviour of a sandstone with comparisons made between the numerical tests and the laboratory tests. The influence of isotropic unloading was investigated, which was found to have impacts on bond breakages and was successfully captured in the 3D shearing processes. It was found that bond breakages correlated strongly with the stress-strain behaviour of the sandstone affecting the peak strength. It was also found that unloading affected the bond breakages, which then changed the mechanical behaviour of sandstone. The tangent stiffnesses of simulated virgin and cored samples under different confining stresses were compared. From the tangent stiffnesses, gross yield envelopes and the yielding surfaces for unloaded samples and virgin samples were plotted and analysed in detail.

  14. Hyperbaric oxygen in skeletal muscle of rats submitted to total acute left hindlimb ischemia: A research report. (United States)

    da Silva, Luis Gustavo Campos; Dalio, Marcelo Bellini; Joviliano, Edwaldo Edner; Feres, Omar; Piccinato, Carlos Eli


    Determine the effect of hyperbaric oxygen treatment in skeletal muscle of rats submitted to total acute left hindlimb ischemia. An experimental study was designed using 48 Wistar rats divided into four groups (n = 12): Control; Ischemia (I)--total hindlimb ischemia for 270 minutes; Hyperbaric oxygen treatment during ischemia (HBO2)--total hindlimb ischemia for 270 minutes and hyperbaric oxygen during the first 90 minutes; Pre-treatment with hyperbaric oxygen (PHBO2)--90 minutes of hyperbaric oxygen treatment before total hindlimb ischemia for 270 minutes. Skeletal muscle injury was evaluated by measuring levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total creatine phosphokinase (CPK); muscular malondialdehyde (MDA), muscular glycogen, and serum ischemia-modified albumin (IMA). AST was significantly higher in I, HBO2 and PHBO2 compared with control (P = .001). There was no difference in LDH. CPK was significantly higher in I, HBO2 and PHBO2, compared with control (p = .014). MDA was significantly higher in PHBO2, compared with other groups (p = .042). Glycogen was significantly decreased in I, HBO2 and PHBO2, compared with control (p < .001). Hyperbaric oxygen treatment in acute total hindlimb ischemia exerted no protective effect on muscle injury, regardless of time of application. When applied prior to installation of total ischemia, hyperbaric oxygen treatment aggravated muscle injury.

  15. Contribution of sucrose transporters to phloem unloading within Sorghum bicolor stem internodes. (United States)

    Milne, Ricky J; Reinders, Anke; Ward, John M; Offler, Christina E; Patrick, John W; Grof, Christopher P L


    Sucrose produced in source leaves is loaded into collection phloem, transported to sinks and unloaded for utilization or storage. In the context of long distance transport, sucrose transporters (SUTs) can function to load sucrose into collection phloem, retrieve leaked sucrose during long distance transport, and load sucrose into sink cells. SUTs have also been proposed to efflux sucrose under conditions of low proton motive force and low extracellular sucrose. The involvement of sucrose transporters in phloem unloading in a representative monocot stem, Sorghum bicolor, was evaluated during different stages of internode development. Transcript levels and functional properties of selected key transporters were measured, with both cellular and subcellular localization determined.

  16. Rapid bedrock uplift in the Antarctic Peninsula explained by viscoelastic response to recent ice unloading

    DEFF Research Database (Denmark)

    Nield, Grace A.; Barletta, Valentina Roberta; Bordoni, Andrea


    Since 1995 several ice shelves in the Northern Antarctic Peninsula have collapsed and triggered ice-mass unloading, invoking a solid Earth response that has been recorded at continuous GPS (cGPS) stations. A previous attempt to model the observation of rapid uplift following the 2002 breakup......×1017–2×1018 Pas – much lower than previously suggested for this region. Combining the LARISSA time series with the Palmer cGPS time series offers a rare opportunity to study the time-evolution of the low-viscosity solid Earth response to a well-captured ice unloading event....

  17. Hindlimb muscle function in turtles: is novel skeletal design correlated with novel muscle function? (United States)

    Mayerl, Christopher J; Pruett, Jenna E; Summerlin, Morgan N; Rivera, Angela R V; Blob, Richard W


    Variations in musculoskeletal lever systems have formed an important foundation for predictions about the diversity of muscle function and organismal performance. Changes in the structure of lever systems may be coupled with changes in muscle use and give rise to novel muscle functions. The two extant turtle lineages, cryptodires and pleurodires, exhibit differences in hindlimb structure. Cryptodires possess the ancestral musculoskeletal morphology, with most hip muscles originating on the pelvic girdle, which is not fused to the shell. In contrast, pleurodires exhibit a derived morphology, in which fusion of the pelvic girdle to the shell has resulted in shifts in the origin of most hip muscles onto the interior of the shell. To test how variation in muscle arrangement might influence muscle function during different locomotor behaviors, we combined measurements of muscle leverage in five major hindlimb muscles with data on muscle use and hindlimb kinematics during swimming and walking in representative semiaquatic cryptodire (Trachemys scripta) and pleurodire (Emydura subglobosa) species. We found substantial differences in muscle leverage between the two species. Additionally, we found that there were extensive differences in muscle use in both species, especially while walking, with some pleurodire muscles exhibiting novel functions associated with their derived musculoskeletal lever system. However, the two species shared similar overall kinematic profiles within each environment. Our results suggest that changes in limb lever systems may relate to changes in limb muscle motor patterns and kinematics, but that other factors must also contribute to differences in muscle activity and limb kinematics between these taxa. © 2017. Published by The Company of Biologists Ltd.

  18. Effect of sedation on fore- and hindlimb lameness evaluation using body-mounted inertial sensors. (United States)

    Rettig, M J; Leelamankong, P; Rungsri, P; Lischer, C J


    Diagnostic analgesia is an integral part of equine lameness examinations, but is challenging to perform in uncooperative horses. Using sedation to facilitate this might, because of analgesic and ataxia-inducing effects, interfere with lameness evaluation. To evaluate whether sedation with low-dose xylazine would alter lameness amplitude as measured by body-mounted inertial sensors. Controlled experiment. Forty-four horses were randomly split into 2 groups. Lameness was measured using body-mounted inertial sensors before and after injection of xylazine (0.3 mg/kg bwt) or saline. Sedation was measured at 5, 20 and 60 min following treatment, and lameness evaluations were performed before (Time 0) and at 20 and 60 min after treatment. Forelimb lameness was determined by measuring the vector sum of mean head height maximum and minimum differences between all right and left forelimb strides (n>25) collected with the horse trotting in a straight line. Hindlimb lameness amplitude was determined by measuring mean pelvic height maximum and minimum differences between right and left hindlimb strides. Numbers of horses staying the same, improving or worsening were compared between groups at each time interval. There were no significant differences in head or pelvic movement asymmetry between xylazine and saline treatment groups. However, a few horses with forelimb lameness in the xylazine treatment group showed a large decrease in head movement asymmetry (decrease in forelimb lameness) at 60 min following sedation. Low-dose sedation with xylazine may be used without the concern of potential lameness-masking effects for hindlimb lameness evaluation, but caution should be used in some horses with forelimb lameness of mild severity. The Summary is available in German - see Supporting information. © 2015 EVJ Ltd.

  19. Effects of FTY720 on Lung Injury Induced by Hindlimb Ischemia Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Liangrong Wang


    Full Text Available Background. Sphingosine-1-phosphate (S1P is a biologically active lysophospholipid mediator involved in modulating inflammatory process. We investigated the effects of FTY720, a structural analogue of S1P after phosphorylation, on lung injury induced by hindlimb ischemia reperfusion (IR in rats. Methods. Fifty Sprague-Dawley rats were divided into groups SM, IR, F3, F5, and F10. Group SM received sham operation, and bilateral hindlimb IR was established in group IR. The rats in groups F3, F5, and F10 were pretreated with 3, 5, and 10 mg/kg/d FTY720 for 7 days before IR. S1P lyase (S1PL, sphingosine kinase (SphK 1, and SphK2 mRNA expressions, wet/dry weight (W/D, and polymorphonuclear/alveolus (P/A in lung tissues were detected, and the lung injury score was evaluated. Results. W/D, P/A, and mRNA expressions of S1PL, SphK1, and SphK2 were higher in group IR than in group SM, while these were decreased in both groups F5 and F10 as compared to IR (p<0.05. The lung tissue presented severe lesions in group IR, which were attenuated in groups F5 and F10 with lower lung injury scores than in group IR (p<0.05. Conclusions. FTY720 pretreatment could attenuate lung injury induced by hindlimb IR by modulating S1P metabolism and decreasing pulmonary neutrophil infiltration.

  20. Effect of denervation on the expression of two glucose transporter isoforms in rat hindlimb muscle.


    Block, N E; Menick, D R; Robinson, K A; Buse, M G


    Denervation rapidly (within 24 h) induces insulin resistance of several insulin-responsive pathways in skeletal muscle, including glucose transport; resistance is usually maximal by 3 d. We examined the effect of denervation on the expression of two glucose transporter isoforms (GLUT-1 and GLUT-4) in rat hindlimb muscle; GLUT-4 is the predominant species in muscle. 1 d postdenervation, GLUT-1 and GLUT-4 mRNA and protein concentrations were unchanged. 3 and 7 d postdenervation, GLUT-4 mRNA and...

  1. Effect of blood flow on muscle lactate release studied in perfused rat hindlimb

    DEFF Research Database (Denmark)

    Pilegaard, H; Bangsbo, Jens; Henningsen, P


    The influence of blood flow on muscle lactate and H+ release as well as muscle glyconeogenesis was studied in the perfused rat hindlimb. After 2 min of supramaximal stimulation the perfusate flow rate was 7 (F7), 12 (F12), or 18 (F18) ml/min for 30 min. Perfusate samples were drawn frequently...... and muscle samples were obtained before stimulation, immediately after stimulation, and at 3, 10, and 30 min of recovery from soleus, white gastrocnemius (WG) and red gastrocnemius. During the first 5 min of recovery lactate release was 35-39% lower (P ... between H+ and lactate release was larger (P blood...

  2. The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft. (United States)

    Wu, Z. Y.; Smithers, B. M.; Parsons, P. G.; Roberts, M. S.


    An isolated rat hindlimb perfusion model carrying xenografts of the human melanoma cell line MM96 was used to study the effects of perfusion conditions on melphalan distribution. Krebs-Henseleit buffer and Hartmann's solution containing 4.7% bovine serum albumin (BSA) or 2.8% dextran 40 were used as perfusates. Melphalan concentrations in perfusate, tumour nodules and normal tissues were measured using high-performance liquid chromatography (HPLC). Increasing the perfusion flow rates (from 4 to 8 ml min(-1)) resulted in higher tissue blood flow (determined with 51Cr-labelled microspheres) and melphalan uptake by tumour and normal tissues. The distribution of melphalan within tumour nodules and normal tissues was similar for both Krebs-Henseleit buffer and Hartmann's solution; however, tissue concentrations of melphalan were significantly higher for a perfusate containing 2.8% dextran 40 than for one containing 4.7% BSA. The melphalan concentration in the tumour was one-third of that found in the skin if the perfusate contained 4.7% BSA. In conclusion, this study has shown that a high perfusion flow enhances the delivery of melphalan into implanted tumour nodules and normal tissues, and a perfusate with low melphalan binding (no albumin) is preferred for maximum uptake of drug by the tumour. PMID:9099965

  3. Spatiotemporal characteristics of 5-HT and dopamine-induced rhythmic hindlimb activity in the in vitro neonatal rat

    DEFF Research Database (Denmark)

    Kiehn, O; Kjaerulff, O


    1. Rhythmic activity was induced with either serotonin (5-HT; 10-100 microM) or dopamine (0.1-1.0 mM), in the in vitro spinal cord preparation of neonatal rats, with one intact hindlimb attached. Patterns of activity were investigated with multiple EMG recordings and the spatiotemporal characteri......1. Rhythmic activity was induced with either serotonin (5-HT; 10-100 microM) or dopamine (0.1-1.0 mM), in the in vitro spinal cord preparation of neonatal rats, with one intact hindlimb attached. Patterns of activity were investigated with multiple EMG recordings and the spatiotemporal...... flexor-extensor transition in older animals. 7. The complex timing of hindlimb muscle activity was relatively unchanged after transecting all dorsal roots. 8. Finally, the relationship between flexor and extensor activity and ventral root discharges was determined. It was found that the L2 ventral root...

  4. Chronic stress decreases cerebrovascular responses during rat hindlimb electrical stimulation

    Directory of Open Access Journals (Sweden)

    Sohee eLee


    Full Text Available Repeated stress is one of the major risk factors for cerebrovascular disease, including stroke and vascular dementia. However, the functional alterations in the cerebral hemodynamic response induced by chronic stress have not been clarified. Here, we investigated the in vivo cerebral hemodynamic changes and accompanying cellular and molecular changes in chronically stressed rats. After three weeks of restraint stress, the elicitation of stress was verified by behavioral despair in the forced swimming test and by physical indicators of stress. The evoked changes in the cerebral blood volume and pial artery responses following hindpaw electrical stimulation were measured using optical intrinsic signal imaging. We observed that, compared to the control group, animals under chronic restraint stress exhibited a decreased hemodynamic response, with a smaller pial arterial dilation in the somatosensory cortex during hindpaw electrical stimulation. The effect of chronic restraint stress on vasomodulator enzymes, including neuronal nitric oxide synthase (nNOS and heme oxygenase-2 (HO-2, was assessed in the somatosensory cortex. Chronic restraint stress downregulated nNOS and HO-2 compared to the control group. In addition, we examined the subtypes of cells that can explain the environmental changes due to the decreased vasomodulators. The expression of parvalbumin in GABAergic interneurons and glutamate receptor-1 in neurons were decreased, whereas the microglial activation was increased. Our results suggest that the chronic stress-induced alterations in cerebral vascular function and the modulations of the cellular expression in the neuro-vasomodulatory system may be crucial contributing factors in the development of various vascular-induced conditions in the brain.

  5. Unloaded shortening velocity of voluntarily and electrically activated human dorsiflexor muscles in vivo.

    Directory of Open Access Journals (Sweden)

    Kazushige Sasaki

    Full Text Available We have previously shown that unloaded shortening velocity (V(0 of human plantar flexors can be determined in vivo, by applying the "slack test" to submaximal voluntary contractions (J Physiol 567:1047-1056, 2005. In the present study, to investigate the effect of motor unit recruitment pattern on V(0 of human muscle, we modified the slack test and applied this method to both voluntary and electrically elicited contractions of dorsiflexors. A series of quick releases (i.e., rapid ankle joint rotation driven by an electrical dynamometer was applied to voluntarily activated dorsiflexor muscles at three different contraction intensities (15, 50, and 85% of maximal voluntary contraction; MVC. The quick-release trials were also performed on electrically activated dorsiflexor muscles, in which three stimulus conditions were used: submaximal (equal to 15%MVC 50-Hz stimulation, supramaximal 50-Hz stimulation, and supramaximal 20-Hz stimulation. Modification of the slack test in vivo resulted in good reproducibility of V(0, with an intraclass correlation coefficient of 0.87 (95% confidence interval: 0.68-0.95. Regression analysis showed that V(0 of voluntarily activated dorsiflexor muscles significantly increased with increasing contraction intensity (R(2 = 0.52, P<0.001. By contrast, V(0 of electrically activated dorsiflexor muscles remained unchanged (R(2<0.001, P = 0.98 among three different stimulus conditions showing a large variation of tetanic torque. These results suggest that the recruitment pattern of motor units, which is quite different between voluntary and electrically elicited contractions, plays an important role in determining shortening velocity of human skeletal muscle in vivo.

  6. Numerical Simulations of Fluid Flow in a Single Fracture under Loading and Unloading Conditions (United States)

    Kling, T.; Huo, D.; Schwarz, J. O.; Enzmann, F.; Blum, P.; Benson, S. M.


    Hydraulic aperture is one of the most important parameters to describe fluid flow in fractured rocks. Hydraulic apertures are typically determined indirectly by fluid flow experiments or hydraulic field tests based on the cubic law. Alternatively, there are different equations approximating an empirical relation between mechanical and hydraulic aperture. However, these methods most widely neglect mechanisms such as stress changes, where increasing stresses decrease the mechanical aperture and, therefore, also the effective hydraulic aperture. Hence, the objective of the present study is to simulate fluid flow in a single fracture under loading/unloading conditions and validate the results with core flooding experiments. Core flooding data and X-ray CT scans (voxel size 0.5 x 0.5 x 1 mm) of a sandstone sample with a single fracture (measured mean aperture of around 0.1 mm) were obtained by laboratory experiments. The fluid flow simulations are performed by solving the incompressible Navier-Stokes equation by using a finite volume method. Input data are given by experimental flow rates, pressures, applied stress levels and CT images of the fracture. In addition, an error analysis is performed to establish confidence in results. Results of the validation exhibit significant effects of stress on aperture distribution such as channeling and stress-dependent fracture permeability. A significant stress sensitivity of hydraulic aperture compared to the mechanical aperture was found, which can be explained by roughness changes resulting from loading. Observations indicate that with increasing stress, changes in mechanical aperture are small, while changes in hydraulic aperture can be very large. Since previous equations for hydraulic aperture do not consider changes in normal stress, a modification of these equations is proposed, including the stress-dependency of mechanical apertures to provide a better approximation to the observed hydraulic apertures.

  7. Positive net movements of amino acids in the hindlimb after overnight food deprivation contribute to sustaining the elevated anabolism of neonatal pigs (United States)

    During the neonatal period, high protein breakdown rate is a metabolic process inherent to elevated rates of protein accretion in skeletal muscle. To determine the relationship between hindlimb net movements of essential and nonessential amino acids in the regulation of hindlimb protein breakdown du...

  8. LAUNCH : an innovation concept for loading and unloading narrow-body airplanes

    NARCIS (Netherlands)

    Grinten, M.P. van der; Bronkhorst, R.E.; Delleman, N.J.


    In wide-body airplanes containers are used for handling luggage in and out the airplane. In narrow-body airplanes loading and unloading still is done manually causing heavy loads in awkward postures due to the limited height in the belly. Incidence rates of musculoskeletal health problems are high

  9. Plastic deformation and contact area of an elastic-plastic contact of ellipsoid bodies after unloading

    NARCIS (Netherlands)

    Jamari, Jamari; Schipper, Dirk J.


    This paper presents theoretical and experimental results of the residual or plastic deformation and the plastic contact area of an elastic–plastic contact of ellipsoid bodies after unloading. There are three regime responses of the deformation and contact area: elastic, elastic–plastic and fully

  10. Micro-Macro Correlations and Anisotropy in Granular Assemblies under Uniaxial Loading and Unloading

    NARCIS (Netherlands)

    Imole, Olukayode Isaiah; Wojtkowski, Mateusz Bronislaw; Magnanimo, Vanessa; Luding, Stefan


    The influence of contact friction on the behavior of dense, polydisperse granular assemblies under uniaxial (oedometric) loading and unloading deformation is studied using discrete element simulations. Even though the uniaxial deformation protocol is one of the “simplest” element tests possible, the

  11. Unloading shoes for osteoarthritis of the knee: protocol for the SHARK randomised controlled trial. (United States)

    Hinman, Rana S; Wrigley, Tim V; Metcalf, Ben R; Hunter, David J; Campbell, Penny; Paterson, Kade; Staples, Margaret P; Bennell, Kim L


    Knee osteoarthritis (OA) is a common and disabling condition. Abnormalities in knee loading play an important role in disease pathogenesis, yet there are few non-surgical treatments for knee OA capable of reducing knee load. This two-arm randomised controlled trial is investigating the efficacy of specially-designed unloading shoes for the treatment of symptoms in people with knee OA. 164 people with symptomatic medial tibiofemoral joint OA will be recruited from the community and randomly allocated to receive either unloading shoes or control shoes. Unloading shoes have a specially-designed triple-density midsole where the medial side is softer than normal and the lateral side harder as well as a lateral wedge between the sole and sock-liner. Control shoes are standard athletic shoes and do not contain these features. Participants will be blinded to shoe allocation and will be instructed to wear the shoes as much as possible every day for 6 months, for a minimum of 4 hours per day. The primary outcomes are knee pain (numerical rating scale) and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index) measured at baseline and 6 months. Secondary outcomes include additional measures of knee pain, knee stiffness, participant global ratings of change in symptoms, quality-of-life and physical activity. The findings from this study will help determine whether specially-designed unloading shoes are efficacious in the management of knee OA. Australian New Zealand Clinical Trials Registry reference: ACTRN12613000851763.

  12. Effect of unloading and loading on power in simulated countermovement and squat jumps

    NARCIS (Netherlands)

    Bobbert, M.F.


    PURPOSE: In the literature, substantial decreases in power output in jumping have been described for both unloading and loading, and these have been attributed to the intrinsic force-velocity-power relationship of muscle. The purpose of this study was to gain a solid understanding of how and why

  13. Effect of a 4-week period of unloaded leg cycling exercise on spasticity in multiple sclerosis. (United States)

    Sosnoff, Jacob; Motl, Robert W; Snook, Erin M; Wynn, Daniel


    We conducted a small pilot study that examined the effect of a 4-week period of unloaded leg cycling on spasticity in individuals with multiple sclerosis (MS). The sample included 22 individuals with MS who were assigned using a quasi-experimental method into either exercise (n = 12) or control (n = 10) conditions. The exercise condition consisted of unloaded leg cycling for 30 minutes per session, 3 times per week, across a 4-week period. The control condition served as a control for passage of time and instrumentation effects. The H-reflex, modified Ashworth scale (MAS), and Multiple Sclerosis Spasticity Scale (MSSS-88) were collected before, 1-day after, and 1 and 4 weeks after the 4-week period. The 4-week period of unloaded leg cycling exercise was not associated with reductions in the H-reflex or MAS, whereas the exercise condition was associated with a reduction in MSSS-88 scores. This pattern of results suggests that chronic, unloaded leg cycling exercise is associated with improvements in spasticity from the participant's perspective, but neither improves nor worsens spasticity from electrophysiological and clinical perspectives.

  14. Myosin heavy chain composition of tiger (Panthera tigris) and cheetah (Acinonyx jubatus) hindlimb muscles. (United States)

    Hyatt, Jon-Philippe K; Roy, Roland R; Rugg, Stuart; Talmadge, Robert J


    Felids have a wide range of locomotor activity patterns and maximal running speeds, including the very fast cheetah (Acinonyx jubatas), the roaming tiger (Panthera tigris), and the relatively sedentary domestic cat (Felis catus). As previous studies have suggested a relationship between the amount and type of activity and the myosin heavy chain (MHC) isoform composition of a muscle, we assessed the MHC isoform composition of selected hindlimb muscles from these three felid species with differing activity regimens. Using gel electrophoresis, western blotting, histochemistry, and immunohistochemistry with MHC isoform-specific antibodies, we compared the MHC composition in the tibialis anterior, medial gastrocnemius (MG), plantaris (Plt), and soleus muscles of the tiger, cheetah, and domestic cat. The soleus muscle was absent in the cheetah. At least one slow (type I) and three fast (types IIa, IIx, and IIb) MHC isoforms were present in the muscles of each felid. The tiger had a high combined percentage of the characteristically slower isoforms (MHCs I and IIa) in the MG (62%) and the Plt (86%), whereas these percentages were relatively low in the MG (44%) and Plt (55%) of the cheetah. In general, the MHC isoform characteristics of the hindlimb muscles matched the daily activity patterns of these felids: the tiger has daily demands for covering long distances, whereas the cheetah has requirements for speed and power. (c) 2009 Wiley-Liss, Inc.

  15. The locomotion of the low spinal cat. I. Coordination within a hindlimb. (United States)

    Forssberg, H; Grillner, S; Halbertsma, J


    Kittens were subjected to a complete transection of the spinal cord (Th 10--12) 1--2 weeks after birth. A few days after the operation they could perform alternating limb movements and somewhat later walking movements with their hindlimbs on a treadmill. The stepcycle of the hindlimbs could be divided into a flexion phase (F) and a first (E1), second (E2) and third (E3) extension phase. The duration of the support phase decreased markedly with treadmill velocity while the swing phase decreased to a much smaller extent. The pattern of electromyographical activity in hip, knee, ankle and toe muscles during treadmill locomotion was very similar to that of the intact cat. This related to both the timing and the general shape of locomotor bursts. The extensor muscles were thus activated well before the placement of the foot and able to produce enough force to support the body. The propulsive thrust in each step was, however, decreased and the animals showed more severe deficits particularly in their equilibrium control. It is concluded, however, that neural networks in the spinal cord (with its peripheral inflow intact but without supraspinal influences) have the capacity to generate a specific and detailed locomotor pattern.

  16. Ontogenetic scaling of the hindlimb muscles of the greater rhea (Rhea americana). (United States)

    Picasso, M B J


    The greater rhea (Rhea americana) is the largest South American bird. It is a cursorial, flightless species with long powerful legs and reduced forelimbs. The goal of this study was to explore how hindlimb muscles scale with body mass during postnatal growth and to analyze whether the specialized locomotion of this species affects the growth of muscle masses. The mass of 19 muscles and body mass were weighed in 21 specimens ranging from 1-month-old individuals to adults. Seventeen muscles scaled with positive allometry with respect to body mass, whereas two muscles scaled isometrically. The predominance of positive allometric growth in hindlimb muscles results in a limb with massive and powerful muscles specialized to support a large body mass and to attain relatively high running speeds. Analysis of muscle mass scaling is a simple and useful way to compare possible differences between locomotor styles, and it is valuable in studies that reconstruct the paleobiology of extinct taxa. © 2014 Blackwell Verlag GmbH.

  17. Ischemic preconditioning of the hindlimb or kidney does not attenuate the severity of acute ischemia/reperfusion-induced pancreatitis in rats. (United States)

    Warzecha, Z; Dembiński, A; Ceranowicz, P; Cieszkowski, J; Konturek, S J; Dembiński, M; Kuśnierz-Cabala, B; Tomaszewska, R; Pawlik, W W


    Ischemic preconditioning of several organs, including the pancreas has been shown to protect these organs from injury evoked by subsequent exposure to severe ischemia followed by reperfusion. Moreover, it has been shown that ischemic preconditioning of distant organs such as the kidney, intestine or limb may protect the heart as effectively as cardiac preconditioning itself. This study was designed to determine whether ischemic preconditioning of the kidney or hindlimb protects the pancreas against ischemia/reperfusion-induced pancreatitis. In male Wistar rats, remote ischemic preconditioning of the pancreas was performed by clamping of right femoral or renal artery twice for 5 min with 5 min interval. Direct ischemic preconditioning was performed by clamping of celiac artery. Thirty min after ischemic preconditioning or sham-operation, acute pancreatitis was induced by clamping of inferior splenic artery for 30 min followed by reperfusion. After 6, 12 h or 1, 2, 3, 5 or 9 days of reperfusion the experiment was ended. Secretory studies were performed 2 h after exposure to direct or remote ischemic preconditioning of the pancreas in conscious rats with chronic pancreatic fistula. Direct ischemic preconditioning of the pancreas applied alone reduced pancreatic exocrine secretion; whereas ischemic preconditioning of the hindlimb or kidney was without effect on pancreatic secretion. Direct ischemic preconditioning of the pancreas attenuated the severity of acute pancreatitis. It was found as a reduction in the pancreatitis-evoked increase in serum activity of lipase and amylase, a decrease in serum concentration of pro-inflammatory interleukin-1beta, diminution of histological signs of pancreatic damage, as well as, an improvement of pancreatic blood flow and DNA synthesis. Remote ischemic preconditioning of the pancreas evoked by short-lasting ischemia of the hindlimb or kidney was without any protective effect in ischemia/reperfusion-induced pancreatitis. Moreover

  18. Attenuation of Hind-Limb Ischemia in Mice with Endothelial-Like Cells Derived from Different Sources of Human Stem Cells (United States)

    Chan, Yau-Chi; Ng, Joyce H. L.; Au, Ka-Wing; Wong, Lai-Yung; Siu, Chung-Wah; Tse, Hung-Fat


    Functional endothelial-like cells (EC) have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC), human embryonic stem cells (hESC-EC) and human induced pluripotent stem cells (hiPSC-EC), and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC) and BM-EC (P>0.05). While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05), the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05). Compared with medium, transplanting BM-EC (n = 6), HUVEC (n = 6), hESC-EC (n = 8) or hiPSC-EC (n = 8) significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as “off-the-shelf” format for the treatment of

  19. Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.

    Directory of Open Access Journals (Sweden)

    Wing-Hon Lai

    Full Text Available Functional endothelial-like cells (EC have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC, human embryonic stem cells (hESC-EC and human induced pluripotent stem cells (hiPSC-EC, and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC and BM-EC (P>0.05. While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05, the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05. Compared with medium, transplanting BM-EC (n = 6, HUVEC (n = 6, hESC-EC (n = 8 or hiPSC-EC (n = 8 significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as "off-the-shelf" format for the treatment

  20. Hydraulic performance of sluice gate with unloaded upstream rotor ...

    African Journals Online (AJOL)

    Swift speed cameras and Tracker software were used to measure the upstream backwater depth and to estimate the instantaneous variation of the rotor speed. The study shows that adding a rotor upstream of the gate caused the upstream water level to increase such that the averaged normalized afflux increased to 1.72 ...

  1. Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin αvβ3 expression.

    Directory of Open Access Journals (Sweden)

    Shen Shen Fu

    Full Text Available BACKGROUND: Human tissue kallikrein (hTK plays an essential role in the physiological and pathological mechanisms of blood vessels. This study aimed to determine whether angiogenesis induced by endothelial progenitor cells (EPCs transduced with the adenovirus-mediated hTK gene could improve blood flow in rat hindlimb ischemia in vivo and to establish a promising mechanism in vitro. METHODS: EPCs transduced with adenovirus encoding hTK-162 (i.e., Ad/hTK-transduced EPCs or Ad/GFP-transduced EPCs were administered to Wister rats with hindlimb ischemia through therapeutic neovascularization. Muscular capillary density (MCD, blood flow (BF, and the number of myofibers were measured at days 7, 14, and 21 after treatment. Expressions of integrin αvβ3 and endothelial nitric oxide synthase (eNOS were detected on the surface of EPCs. RESULTS: MCD, BF, and the number of myofibers in rats with Ad/hTK-transduced EPCs remarkably increased at day 21 after treatment compared with rats with Ad/GFP-transduced EPCs or the control group (P<0.01. Expressions of integrin αvβ3 and eNOS protein on the surface of EPCs also increased in rats with Ad/hTK-transduced EPCs. The levels of integrin αvβ3 expression were reduced by PI3K and eNOS blockade, and the inhibitor of integrin αvβ3 abrogated the migration and adhesion of hTK-transduced EPCs (P<0.05. CONCLUSION: hTK gene delivery in vivo improves the natural angiogenic response to ischemia. The ability of hTK gene-transduced EPCs can be enhanced in vitro, in which integrin αvβ3 plays a role in the process.

  2. Combination of cyclosporin A and prednisolone for juvenile cellulitis concurrent with hindlimb paresis in 3 English cocker spaniel puppies. (United States)

    Park, Chul; Yoo, Jong-Hyun; Kim, Ha-Jung; Kang, Byeong-Teck; Park, Hee-Myung


    Three 7-week-old, English cocker spaniel littermates were diagnosed as having juvenile cellulitis with concurrent neurologic signs based on history, histopathology, and therapeutic response. The puppies were treated with cyclosporin A and prednisolone. Skin lesions and hindlimb paresis improved following treatment.

  3. An in vivo Experimental System to Study Sugar Phloem Unloading in Ripening Grape Berries During Water Deficiency Stress (United States)



    An in vivo experimental system—called the ‘berry‐cup’ technique—was developed to study sugar phloem unloading and the accumulation of sugar in ripening grape berries. The berry‐cup system consists of a single peeled grape berry immersed in a buffer solution in a cup prepared from a polypropylene syringe. A small cross‐incision (2 mm in length) is made on the stylar remnant of a berry during its ripening phase, the skin of the berry then being easily peeled off, exposing the dorsal vascular bundles without damaging either these or the pulp tissue of the berry. The sites of sugar phloem unloading are thus made directly accessible and may be regulated by the buffer solution. In addition, the unloaded photoassimilates are easily transported into the buffer solution in the berry‐cup. With the berry‐cup technique, it takes 60 min to purge the sugar already present in the apoplast, after which the amount of sugar in the buffer solution is a direct measure of the sugar unloading from the grape berry phloem. The optimum times for sampling were 20 or 30 min, depending on the type of experiment. Sugar phloem unloading was significantly inhibited by the inclusion of either 7·5 mm NaF or 2·5 mm PCMB in the buffer solution. This study indicates that sugar phloem unloading in ripening grape berries is via the apoplastic network and that the process requires the input of energy. The system was shown to be an appropriate experimental system with which to study sugar phloem unloading in ripening grape berries, and was applied successfully to the study of berry sugar unloaded from grapevines subjected to water stress. The results showed that water deficiency inhibits sugar unloading in grape berries. PMID:12907466

  4. Effects of unloading on knee articular cartilage T1rho and T2 magnetic resonance imaging relaxation times: a case series. (United States)

    Souza, Richard B; Baum, Thomas; Wu, Samuel; Feeley, Brian T; Kadel, Nancy; Li, Xiaojuan; Link, Thomas M; Majumdar, Sharmila


    Case series. It has been shown in rodent and canine models that cartilage composition is significantly altered in response to long-term unloading. To date, however, no in vivo human studies have investigated this topic. The objective of this case series was to determine the influence of unloading and reloading on T1rho and T2 relaxation times of articular cartilage in healthy young joints. Ten patients who required 6 to 8 weeks of non-weight bearing (NWB) for injuries affecting the distal lower extremity participated in the study. Quantitative T1rho and T2 imaging of the ipsilateral knee joint was performed at 3 time points: (1) prior to surgery (baseline), (2) immediately after a period of NWB (post-NWB), and (3) after 4 weeks of full weight bearing (post-FWB). Cartilage regions of interest were segmented and overlaid on T1rho and T2 relaxation time maps for quantification. Descriptive statistics are provided for all changes. Increases of 5% to 10% in T1rho times of all femoral and tibial compartments were noted post-NWB. All values returned to near-baseline levels post-FWB. Increases in medial tibia T2 times were noted post-NWB and remained elevated post-FWB. The load-bearing regions showed the most significant changes in response to unloading, with increases of up to 12%. The observation of a transient shift in relaxation times confirms that cartilage composition is subject to alterations based on loading conditions. These changes appear to be mostly related to proteoglycan content and more localized to the load-bearing regions. However, following 4 weeks of full weight bearing, relaxation times of nearly all regions had returned to baseline levels, demonstrating reversibility in compositional fluctuations. Therapy, level 4.

  5. Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension (United States)

    Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.


    The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass of plantaris and soleus of a rats in hindlimb suspension, and on the isomyosin expression in these muscles, was investigated in young female rats divided into four groups: normal control (NC), normal steroid (NS), normal suspension (N-sus), and suspension steroid (sus-S). Steroid treatment of suspended animals (sus-S vs N-sus) was found to partially spare body weight and muscle weight, as well as myofibril content of plantaris (but not soleus), but did not modify the isomyosin pattern induced by suspension. In normal rats (NS vs NC), steroid treatment did enhance body weight and plantaris muscle weight; the treatment did not alter isomyosin expression in either muscle type.

  6. Atrophy and growth failure of rat hindlimb muscles in tail-cast suspension (United States)

    Jaspers, S. R.; Tischler, M. E.


    The primary objective of the present study is related to an evaluation of a modified tail-cast suspension model as a means of identifying metabolic factors which control or are associated with muscle atrophy and growth failure. Two different control conditions (normal and tail-casted weight bearing) were studied to determine the appropriate control for tail-cast suspension. A description is presented of a model which is most useful for studying atrophy of hindlimb muscles under certain conditions. Female Sprague-Dawley rats were employed in the experiments. Attention is given to growth rate and urinary excretion of urea and ammonia in different types of rats, the relationship between body weight and skeletal muscle weight, and the relationship between animal body weight and rates of protein synthesis and protein degradation.

  7. Direct comparison of unloading compliance and potential drop techniques in J-integral testing

    Energy Technology Data Exchange (ETDEWEB)

    McGowan, J.J.; Nanstad, R.K.


    Single-specimen J-integral testing is performed commonly with the unloading compliance technique. Use of modern instrumentation techniques and powerful desktop computers have made this technique a standard. However, this testing technique is slow and tedious, with the loading rate fixed at a slow quasi-static rate. For these reasons the dc potential drop technique was investigated for crack length measurement during a J-integral test. For direct comparison, both unloading compliance and potential drop were used simultaneously during a J-integral test. The results showed good agreement between the techniques. However, the potential drop technique showed an offset in crack length due to plastic blunting processes. Taking this offset into account, J/sub Ic/ values calculated by both techniques compared well.

  8. Mechanics of load-drag-unload contact cleaning of gecko-inspired fibrillar adhesives. (United States)

    Abusomwan, Uyiosa A; Sitti, Metin


    Contact self-cleaning of gecko-inspired synthetic adhesives with mushroom-shaped tips has been demonstrated recently using load-drag-unload cleaning procedures similar to that of the natural animal. However, the underlying mechanics of contact cleaning has yet to be fully understood. In this work, we present a detailed experiment of contact self-cleaning that shows that rolling is the dominant mechanism of cleaning for spherical microparticle contaminants, during the load-drag-unload procedure. We also study the effect of dragging rate and normal load on the particle rolling friction. A model of spherical particle rolling on an elastomer fibrillar adhesive interface is developed and agrees well with the experimental results. This study takes us closer to determining design parameters for achieving self-cleaning fibrillar adhesives.

  9. Forelimb and hindlimb ground reaction forces of walking cats: assessment and comparison with walking dogs. (United States)

    Corbee, R J; Maas, H; Doornenbal, A; Hazewinkel, H A W


    The primary aim of this study was to assess the potential of force plate analysis for describing the stride cycle of the cat. The secondary aim was to define differences in feline and canine locomotion based on force plate characteristics. Ground reaction forces of 24 healthy cats were measured and compared with ground reaction forces of 24 healthy dogs. Force-time waveforms in cats generated by force plate analysis were consistent, as reflected by intra-class correlation coefficients for peak vertical force, peak propulsive force and peak braking force (0.94-0.95, 0.85-0.89 and 0.89-0.90, respectively). Compared with dogs, cats had a higher peak vertical force during the propulsion phase (cat, 3.89 ± 0.19 N/kg; dog, 3.03 ± 0.16 N/kg), and a higher hindlimb propulsive force (cat, -1.08 ± 0.13 N/kg; dog, (-0.87 ± 0.13 N/kg) and hindlimb impulse (cat, -0.18 ± 0.03 N/kg; dog, -0.14 ± 0.02 N/kg). Force plate analysis is a valuable tool for the assessment of locomotion in cats, because it can be applied in the clinical setting and provides a non-invasive and objective measurement of locomotion characteristics with high repeatability in cats, as well as information about kinetic characteristics. Differences in force-time waveforms between cats and dogs can be explained by the more crouched position of cats during stance and their more compliant gait compared with dogs. Feline waveforms of the medio-lateral ground reaction forces also differ between cats and dogs and this can be explained by differences in paw supination-pronation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Hindlimb movement in the cat induced by amplitude-modulated stimulation using extra-spinal electrodes (United States)

    Tai, Changfeng; Wang, Jicheng; Shen, Bing; Wang, Xianchun; Roppolo, James R.; de Groat, William C.


    Hindlimb movement in the cat induced by electrical stimulation with an amplitude-modulated waveform of the dorsal surface of the L5-S1 spinal cord or the L5-S1 dorsal/ventral roots was investigated before and after acute spinal cord transection at the T13-L1 level. Stimulation of the spinal cord or dorsal/ventral root at the same spinal segment induced similar movements including coordinated multi-joint flexion or extension. The induced movements changed from flexion to extension when the stimulation was moved from rostral (L5) to caudal (S1) spinal segments. Stimulation of a dorsal or ventral root on one side induced only ipsilateral hindlimb movement. However, stimulation on the dorsal surface of the spinal cord along the midline or across the spinal cord induced bilateral movements. The extension induced by stimulation of L7 dorsal root produced the largest ground reaction force that was strong enough to support body weight. Dorsal root stimulation induced a larger ground reaction force than ventral root stimulation and produced a more graded recruitment curve. Stepping at different speeds could be generated by combined stimulation of the rostral (L5) and the caudal (L6/L7) spinal segments with an appropriate timing between the different stimulation channels. Acute transection of the spinal cord did not change the responses indicating that the induced movements did not require the involvement of the supraspinal locomotor centers. The methods and the stimulation strategy developed in this study might be utilized to restore locomotor function after spinal cord injury.



    Dorota Janiszewska; Kamila Kozieł; Bogusław Pawlikowski


    In this study characterization of sensory and physical-chemical properties of representative samples of technological waste water after hydraulic unloading fish from fishing vessels, including fishing boats equipped with RSW (Refrigerated Sea Water System) or CSW (Chilling Sea Water System) system was described. Sensory quality and analytical determinations in technological waste water samples was analyzed. They demonstrated that their sensory quality attributes and physical-chemical properti...

  12. Changes in muscle strength and morphology after muscle unloading in Special Forces missions

    DEFF Research Database (Denmark)

    Thorlund, J B; Jakobsen, O; Madsen, T


    ) and immediately after (post1) an 8-day simulated special support and reconnaissance (SSR) mission and after 3 h of active recovery (post2). Maximal muscle strength (MVC) and rate of force development (RFD) were measured along with maximal counter movement jump height (JH). Muscle biopsies were obtained from...... the vastus lateralis at pre and post1. Acute reductions were found in MVC (11%), JH (10%) and RFD (17-22%) after 8 days of muscle unloading (post1) (P...

  13. Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy (United States)

    Marzuca-Nassr, Gabriel Nasri; Martins, Amanda Roque; Vitzel, Kaio Fernando; Crisma, Amanda Rabello; Torres, Rosângela Pavan; Mancini-Filho, Jorge; Kang, Jing Xuan; Curi, Rui


    The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p Fat-1 mice had lower soleus muscle dry mass loss (by 10%) and preserved absolute isotonic force (by 17%) and CSA of the soleus muscle (by 28%) after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70%) and MuRF-1 content decreased (by 50%) in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition. PMID:28984836

  14. Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy

    Directory of Open Access Journals (Sweden)

    Gabriel Nasri Marzuca-Nassr


    Full Text Available The consequences of two-week hindlimb suspension (HS on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA, and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2 and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1 were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively, muscle isotonic and tetanic force (by 29% and 18%, respectively, CSA of the soleus muscle (by 36%, and soleus muscle fibers (by 45%. Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001. Fat-1 mice had lower soleus muscle dry mass loss (by 10% and preserved absolute isotonic force (by 17% and CSA of the soleus muscle (by 28% after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70% and MuRF-1 content decreased (by 50% in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

  15. Non-random nectar unloading interactions between foragers and their receivers in the honeybee hive (United States)

    Goyret, Joaquín; Farina, Walter M.


    Nectar acquisition in the honeybee Apis mellifera is a partitioned task in which foragers gather nectar and bring it to the hive, where nest mates unload via trophallaxis (i.e. mouth-to-mouth transfer) the collected food for further storage. Because forager mates exploit different feeding places simultaneously, this study addresses the question of whether nectar unloading interactions between foragers and hive-bees are established randomly, as it is commonly assumed. Two groups of foragers were trained to exploit a different scented food source for 5 days. We recorded their trophallaxes with hive-mates, marking the latter ones according to the forager group they were unloading. We found non-random probabilities for the occurrence of trophallaxes between experimental foragers and hive-bees, instead, we found that trophallactic interactions were more likely to involve groups of individuals which had formerly interacted orally. We propose that olfactory cues present in the transferred nectar promoted the observed bias, and we discuss this bias in the context of the organization of nectar acquisition: a partitioned task carried out in a decentralized insect society.

  16. Severe metallosis and elevated chromium in serum following implantation of the joint unloading implant system. (United States)

    Wolff, Matthias; Haasper, Carl; Zahar, Akos; Gauck, Christian; Gehrke, Thorsten; Citak, Mustafa


    In recent years, the minimally invasive joint-preserving implant system has been developed. The main goal of this device is to unload the medial knee compartment without affecting the lateral compartment. The current authors describe a severe metallosis and elevated chromium in serum following implantation of the joint unloading implant system of a 50-year-old male patient, presented to our hospital 3 years after implantation of a KineSpring System into his left knee due to unicompartmental medial osteoarthritis (OA) in an external hospital. Radiographs showed radiological signs for loosening of the screws in the tibia and a progressive OA on the medial and patellofemoral compartments. Revision surgery with removing of the unloading device was performed at our hospital. The intraoperative situs presented a severe metallosis around the device. Five days after revision surgery, the laboratory parameters revealed an elevated value for chromium in serum, while nickel and cobalt values in serum were normal. Reliable clinical data about the long-term results of the KineSpring System is desperately needed. Further studies are warranted to work out the effects of cobalt and chromium levels and further side effects following the implantation of the extra-articular absorber system.

  17. Unloading knee brace is a cost-effective method to bridge and delay surgery in unicompartmental knee arthritis


    Lee, Paul YF; Winfield, Thomas G; Harris, Shaun RS; Storey, Emerald; Chandratreya, Amit


    Background Unloading knee braces can provide good short-term pain relief for some patients with unicompartmental osteoarthritis (UOA). Their cost is relatively small compared with surgical interventions. However, no previous studies have reported their use over a duration of 5 years or more. Methods Up to 8 years of prospective data were collected from 63 patients who presented with UOA. After conservative management with analgesia and physiotherapy, patients were offered an unloading brace. ...

  18. Agonist muscle adaptation accompanied by antagonist muscle atrophy in the hindlimb of mice following stretch-shortening contraction training. (United States)

    Rader, Erik P; Naimo, Marshall A; Ensey, James; Baker, Brent A


    The vast majority of dynamometer-based animal models for investigation of the response to chronic muscle contraction exposure has been limited to analysis of isometric, lengthening, or shortening contractions in isolation. An exception to this has been the utilization of a rat model to study stretch-shortening contractions (SSCs), a sequence of consecutive isometric, lengthening, and shortening contractions common during daily activity and resistance-type exercise. However, the availability of diverse genetic strains of rats is limited. Therefore, the purpose of the present study was to develop a dynamometer-based SSC training protocol to induce increased muscle mass and performance in plantarflexor muscles of mice. Young (3 months old) C57BL/6 mice were subjected to 1 month of plantarflexion SSC training. Hindlimb muscles were analyzed for muscle mass, quantitative morphology, myogenesis/myopathy relevant gene expression, and fiber type distribution. The main aim of the research was achieved when training induced a 2-fold increase in plantarflexion peak torque output and a 19% increase in muscle mass for the agonist plantaris (PLT) muscle. In establishing this model, several outcomes emerged which raised the value of the model past that of being a mere recapitulation of the rat model. An increase in the number of muscle fibers per transverse muscle section accounted for the PLT muscle mass gain while the antagonist tibialis anterior (TA) muscle atrophied by 30% with preferential atrophy of type IIb and IIx fibers. These alterations were accompanied by distinct gene expression profiles. The findings confirm the development of a stretch-shortening contraction training model for the PLT muscle of mice and demonstrate that increased cross-sectional fiber number can occur following high-intensity SSC training. Furthermore, the TA muscle atrophy provides direct evidence for the concept of muscle imbalance in phasic non-weight bearing muscles, a concept largely

  19. Mechanical Unloading of Mouse Bone in Microgravity Significantly Alters Cell Cycle Gene Set Expression (United States)

    Blaber, Elizabeth; Dvorochkin, Natalya; Almeida, Eduardo; Kaplan, Warren; Burns, Brnedan


    Spaceflight factors, including microgravity and space radiation, have many detrimental short-term effects on human physiology, including muscle and bone degradation, and immune system dysfunction. The long-term progression of these physiological effects is still poorly understood, and a serious concern for long duration spaceflight missions. We hypothesized that some of the degenerative effects of spaceflight may be caused in part by an inability of stem cells to proliferate and differentiate normally resulting in an impairment of tissue regenerative processes. Furthermore, we hypothesized that long-term bone tissue degeneration in space may be mediated by activation of the p53 signaling network resulting in cell cycle arrest and/or apoptosis in osteoprogenitors. In our analyses we found that spaceflight caused significant bone loss in the weight-bearing bones of mice with a 6.3% reduction in bone volume and 11.9% decrease in bone thickness associated with increased osteoclastic activity. Along with this rapid bone loss we also observed alterations in the cell cycle characterized by an increase in the Cdkn1a/p21 cell cycle arrest molecule independent of Trp53. Overexpression of Cdkn1a/p21 was localized to osteoblasts lining the periosteal surface of the femur and chondrocytes in the head of the femur, suggesting an inhibition of proliferation in two key regenerative cell types of the femur in response to spaceflight. Additionally we found overexpression of several matrix degradation molecules including MMP-1a, 3 and 10, of which MMP-10 was localized to osteocytes within the shaft of the femur. This, in conjunction with 40 nm resolution synchrotron nano-Computed Tomography (nano-CT) observations of an increase in osteocyte lacunae cross-sectional area, perimeter and a decrease in circularity indicates a potential role for osteocytic osteolysis in the observed bone degeneration in spaceflight. To further investigate the genetic response of bone to mechanical

  20. Experimental study on the response characteristics of coal permeability to pore pressure under loading and unloading conditions (United States)

    Ye, Zhiwei; Zhang, Lei; Hao, Dingyi; Zhang, Cun; Wang, Chen


    In order to study the response characteristics of coal permeability to pore pressure, seepage experiments under different simulated in situ stresses on loading and unloading paths are carried out using the self-developed Gas Flow and Displacement Testing Apparatus (GFDTA) system. Based on the analysis of the experimental data, the relationship between average pore pressure and permeability is found to basically obey the function distribution of a two degree polynomial. In this paper, two aspects of the relationship between permeability and pore pressure are explained: the Klinbenberg effect and expansion, and the penetration of the initial fracture. Under low pore pressure, the decrease in the Klinbenberg effect is the main reason for the decrease in permeability with increased pore pressure. Under relatively high pore pressure, the increase in pore pressure leads to the initial fracture expansion and penetration of the coal sample, which causes an increase in permeability. In order to evaluate the sensitivity of the permeability response to pore pressure changes, the permeability dispersion and pore pressure sensitivity coefficients are defined. After the sensitivity analysis, it was concluded that the loading history changed the fracture structure of the original coal sample and reduced its permeability sensitivity to pore pressure. Under low pore pressure, the Klinbenberg effect is the reason for the decrease in pore pressure sensitivity. Lastly, the permeability-pore pressure relationship is divided into three stages to describe the different response characteristics individually.

  1. A clinical case of neosporosis in a 4-week-old holstein friesian calf which developed hindlimb paresis postnatally. (United States)

    Uesaka, Karin; Koyama, Kenji; Horiuchi, Noriyuki; Kobayashi, Yoshiyasu; Nishikawa, Yoshifumi; Inokuma, Hisashi


    A 4-week-old female Holstein Friesian calf presented with hindlimb paresis. Neurologic examination of spinal reflexes revealed depressed or absent reflexes of the hindlimbs. Menace responses on both sides disappeared on examination of cranial nerves. The calf was finally diagnosed with Neospora caninum infection by pathological findings including nonsuppurative inflammation associated with cysts in the cerebrum and spinal cord. High levels of antibody against recombinant surface antigen 1 of N. caninum (NcSAG1) were detected by ELISA from both serum and cerebrospinal fluid (CSF) samples. This result suggests that detection of antibodies against N. caninum by NcSAG1-ELISA in serum and CSF could be useful for the clinical diagnosis of neosporosis in calves with acquired neurological signs.

  2. Roles for C-X-C chemokines and C5a in lung injury after hindlimb ischemia-reperfusion

    DEFF Research Database (Denmark)

    Bless, N M; Warner, R L; Padgaonkar, V A


    We evaluated the roles of the C-X-C chemokines cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) as well as the complement activation product C5a in development of lung injury after hindlimb ischemia-reperfusion in rats. During reperfusion, CD11b...... permeability and decreased lung myeloperoxidase content by 93 and 68%, respectively (P C5a-related neutrophil chemotactic activity. Treatment with anti-C5a decreased lung vascular permeability, lung myeloperoxidase, and BAL CINC by 51......, 58, and 23%, respectively (P C5a are required for lung neutrophil recruitment and full induction of lung injury after hindlimb ischemia-reperfusion in rats....

  3. Reduced BMP signaling results in hindlimb fusion with lethal pelvic/urogenital organ aplasia: a new mouse model of sirenomelia.

    Directory of Open Access Journals (Sweden)

    Kentaro Suzuki

    Full Text Available Sirenomelia, also known as mermaid syndrome, is a developmental malformation of the caudal body characterized by leg fusion and associated anomalies of pelvic/urogenital organs including bladder, kidney, rectum and external genitalia. Most affected infants are stillborn, and the few born alive rarely survive beyond the neonatal period. Despite the many clinical studies of sirenomelia in humans, little is known about the pathogenic developmental mechanisms that cause the complex array of phenotypes observed. Here, we provide new evidences that reduced BMP (Bone Morphogenetic Protein signaling disrupts caudal body formation in mice and phenocopies sirenomelia. Bmp4 is strongly expressed in the developing caudal body structures including the peri-cloacal region and hindlimb field. In order to address the function of Bmp4 in caudal body formation, we utilized a conditional Bmp4 mouse allele (Bmp4(flox/flox and the Isl1 (Islet1-Cre mouse line. Isl1-Cre is expressed in the peri-cloacal region and the developing hindimb field. Isl1Cre;Bmp4(flox/flox conditional mutant mice displayed sirenomelia phenotypes including hindlimb fusion and pelvic/urogenital organ dysgenesis. Genetic lineage analyses indicate that Isl1-expressing cells contribute to both the aPCM (anterior Peri-Cloacal Mesenchyme and the hindlimb bud. We show Bmp4 is essential for the aPCM formation independently with Shh signaling. Furthermore, we show Bmp4 is a major BMP ligand for caudal body formation as shown by compound genetic analyses of Bmp4 and Bmp7. Taken together, this study reveals coordinated development of caudal body structures including pelvic/urogenital organs and hindlimb orchestrated by BMP signaling in Isl1-expressing cells. Our study offers new insights into the pathogenesis of sirenomelia.

  4. Hindlimb musculature of the largest living rodent Hydrochoerus hydrochaeris (Caviomorpha): Adaptations to semiaquatic and terrestrial styles of life. (United States)

    García-Esponda, César M; Candela, Adriana M


    The caviomorph species Hydrochoerus hydrochaeris (Cavioidea), or capybara, is the largest living rodent. This species is widely distributed, from northern South America to Uruguay and eastern Argentina, inhabiting in a wide variety of densely vegetated lowlands habitats in the proximity of water. Hydrochoerus hydrochaeris not only runs with agility, like other members of the Cavioidea, but it can also swim and dive easily. For these reasons, it has been classified as a cursorial as well as semiaquatic species. However, comprehensive anatomical descriptions of the osteology and myology of the capybara are not available in the literature and analyses on its swimming abilities are still required. We hypothesize that some of the characters of the hindlimb of H. hydrochaeris could reveal a unique morphological arrangement associated with swimming abilities. In this study, an anatomical description of the hindlimb musculature of H. hydrochaeris, and a discussion of the possible functional significance of the main muscles is provided. In addition, we explore the evolution of some myological and osteological characters of the capybara in the context of the cavioids. We concluded that most of the muscular and osteological features of the hindlimb of H. hydrochaeris are neither adaptations to a specialized cursoriality, nor major modifications for an aquatic mode of life. Hydrochoerus hydrochaeris share several features with other cavioids, being a generalized cursorial species in the context of this clade. However, it shows some adaptations of the hindlimb for enhancing propulsion through water, of which the most notable seems to be the shortening of the leg, short tendons of most muscles of the leg, and a well-developed soleus muscle. These adaptations to a semiaquatic mode of life could have been acquired during the most recent evolutionary history of the hydrochoerids. © 2015 Wiley Periodicals, Inc.

  5. Comparative functional anatomy of hindlimb muscles and bones with reference to aquatic adaptation of the sea otter


    MORI, Kent; Suzuki, Satoshi; KOYABU, Daisuke; Kimura, Junpei; HAN, Sung-Yong; Endo, Hideki


    Although the sea otter (Enhydra lutris) is a complete aquatic species, spending its entire life in the ocean, it has been considered morphologically to be a semi-aquatic animal. This study aimed to clarify the unique hindlimb morphology and functional adaptations of E. lutris in comparison to other Mustelidae species. We compared muscle mass and bone measurements of five Mustelidae species: the sea otter, Eurasian river otter (Lutra lutra), American mink (Neovison vison), Japanese weasel (Mus...

  6. Dynamic "Range of Motion" Hindlimb Stretching Disrupts Locomotor Function in Rats with Moderate Subacute Spinal Cord Injuries. (United States)

    Keller, Anastasia; Rees, Kathlene; Prince, Daniella; Morehouse, Johnny; Shum-Siu, Alice; Magnuson, David


    Joint contractures and spasticity are two common secondary complications of a severe spinal cord injury (SCI), which can significantly reduce quality of life, and stretching is one of the top strategies for rehabilitation of these complications. We have previously shown that a daily static stretching protocol administered to rats at either acute or chronic time points after a moderate or moderate-severe T10 SCI significantly disrupts their hindlimb locomotor function. The objective of the current study was to examine the effects of dynamic range of motion (ROM) stretching on the locomotor function of rats with SCI as an alternative to static stretching. Starting at 6 weeks post-injury (T10 moderate contusion) eight adult Sprague-Dawley rats were subjected to hindlimb stretching for 4 weeks. Our standard stretching protocol (six maneuvers to stretch the major hindlimb muscle groups) was modified from 1 min static stretch-and-hold at the end ROM of each stretch position to a dynamic 2 sec hold, 1 sec release rhythm repeated for a duration of 1 min. Four weeks of daily (5 days/week) dynamic stretching led to significant disruption of locomotor function as assessed by the Basso, Beattie, Bresnahan (BBB) Open Field Locomotor Scale and three-dimensional (3D) kinematic and gait analyses. In addition, we identified and analyzed an apparently novel hindlimb response to dynamic stretch that resembles human clonus. The results of the current study extend the observation of the stretching phenomenon to a new modality of stretching that is also commonly used in SCI rehabilitation. Although mechanisms and clinical relevance still need to be established, our findings continue to raise concerns that stretching as a therapy can potentially hinder aspects of locomotor recovery.

  7. The Louisville Swim Scale: A Novel Assessment of Hindlimb Function following Spinal Cord Injury in Adult Rats (United States)

    Smith, Rebecca R.; Burke, Darlene A.; Baldini, Angela D.; Shum-Siu, Alice; Baltzley, Ryan; Bunger, Michelle; Magnuson, David S.K.


    The majority of animal studies examining the recovery of function following spinal cord injury use the BBB Open-Field Locomotor Scale as a primary outcome measure. However, it is now well known that rehabilitation strategies can bring about significant improvements in hindlimb function in some animal models. Thus, improvements in walking following spinal cord injury in rats may be influenced by differences in activity levels and housing conditions during the first few weeks post-injury. Swimming is a natural form of locomotion that animals are not normally exposed to in the laboratory setting. We hypothesized that deficits in, and functional recovery of, swimming would accurately represent the locomotor capability of the nervous system in the absence of any retraining effects. To test this hypothesis, we have compared the recovery of walking and swimming in rats following a range of standardized spinal cord injuries and two different retraining strategies. In order to assess swimming, we developed a rating system we call the Louisville Swimming Scale (LSS) that evaluates three characteristics of swimming that are highly altered by spinal cord injury— namely, hindlimb movement, forelimb dependency, and body position. The data indicate that the LSS is a sensitive and reliable method of determining swimming ability and the improvement in hindlimb function after standardized contusion injury of the thoracic spinal cord. Furthermore, the data suggests that when used in conjunction with the BBB Open-field Locomotor Scale, the LSS assesses locomotor capabilities that are not influenced by a retraining effect. PMID:17115911

  8. Correlation of Loaded and Unloaded Foot Area With Arch Index in Younger Flatfoot

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    Wibowo Dwi Basuki


    Full Text Available Harris & Beath claimed 23% of human kind population is indicated flatfoot. Identifying flatfoot is by using wet foot test. This footprint is not accurate because of the difficulty to make sure the patient stand upright. Another way is using x-ray to determine height of arch which is a distance from medial longitudinal foot arch to the ground. If the distance is less than certain level, so the foot type is included as flatfoot. Other method proposed by Kulkarni et al. using the footprint index (FPI which is the ratio of B intercept to A intercept, where the footprint was obtained from pedobarography image. If FPI is lower than 0.63, it is categorized as flatfoot. Another method to determine arch type which is widely used is Cavanagh’s Arch Index (AI from division of mid foot area to entire footprint area (excluding the toes. If AI>0.26, then the foot type is flatfoot. This study is to learn the correlation between entire loaded and unloaded foot area with Cavanag’s AI. The entire loaded foot and footprint area for evaluating AI derived from a digital footprint modified from document scanner, while the entire unloaded foot area derived from a 3D scanner for foot orthotic. One hundred and two healthy asked voluntarily for doing footprint. From 102 subjects found 63 participants identified as flatfoot, 31 subjects are normal feet and 8 subjects identified as high arch. A series of 3 x 3 repeated measures ANOVAs were used to determine statistical differences (α<0.05. A significant interaction existed between ratio of entire loaded and unloaded foot area (RFA subject to all categories of AI (p<0.05 also a correlation coefficient of r=0.67 has found between RFA and AI on foot type of flatfoot which means that flatfoot can be indicated by RFA.

  9. Modelling of flow in the unloading slot of the control valve (United States)

    Mrózek, Lukáš; Tajč, Ladislav


    The flow in the unloading system of the control valve is modelled. Values of the flow coefficient for various slot widths and openings are evaluated. The changes of pressure in the spaces of the valve are recorded when the performance of the turbine is regulated and its impacts on the level of the stabilizing power at the given setting of the cone lift are evaluated. The results from experiments on the air model of the system are compared with the pressures measured on the model of the valve. The operational characteristics of the experimental steam turbine is considered.

  10. Study on loading and unloading performance of new energy vehicle battery sensor (United States)

    Wu, Bin; Ren, Kai; Liu, Ying


    This paper first introduces the 18650 battery, describes the importance of the battery temperature sensor, uses Ansys Workbench finite element simulation software and the mean of the combination of displacement constraint and reaction force, studies the force and the size of the change of new energy vehicle battery temperature sensor in the loading, translation and unloading of the three cases, then make the test to verify its accuracy. At last, the test results are compared with the usual maximum acceleration of the vehicle in driving which verified the sensor of the car will not fall off in the car driving process and work normally.

  11. Responses of skeletal muscles to gravitational unloading and/or reloading. (United States)

    Ohira, Takashi; Kawano, Fuminori; Ohira, Tomotaka; Goto, Katsumasa; Ohira, Yoshinobu


    Adaptation of morphological, metabolic, and contractile properties of skeletal muscles to inhibition of antigravity activities by exposure to a microgravity environment or by simulation models, such as chronic bedrest in humans or hindlimb suspension in rodents, has been well reported. Such physiological adaptations are generally detrimental in daily life on earth. Since the development of suitable countermeasure(s) is essential to prevent or inhibit these adaptations, effects of neural, mechanical, and metabolic factors on these properties in both humans and animals were reviewed. Special attention was paid to the roles of the motoneurons (both efferent and afferent neurograms) and electromyogram activities as the neural factors, force development, and/or length of sarcomeres as the mechanical factors and mitochondrial bioenergetics as the metabolic factors.

  12. [Clinical relevance of unloading in cartilage therapy of the knee--shoe insoles, knee braces or additional operative procedure?]. (United States)

    Kraus, T M; Imhoff, A B; Ateschrang, A; Stöckle, U; Schröter, S


    Restoration of a neutral biomechanical environment and reduction of overload is an important factor contributing to the success of any cartilage repair procedure. Reduction of overload can by achieved by so called unloading procedures in order to reduce intraarticular pressure from the repair zone. Unloading can be achieved via loss of weight, wedged shoe insoles, knee braces or via operations such as osteotomies around the knee joint. The cartilage therapy and the concomitant unloading procedure should be adapted to the individual pathology and realistic aims of the patient. Wedged insoles and braces are the least invasive treatment methods. In comparison, however, beneficial effects of braces outline those of laterally wedged heels. Nevertheless long-term compliance with insoles and braces is poor. Concerning braces either because the positive effects of the braces are too small or because the adverse effects are too large. Unloading in the long run may only be achieved through operative procedures. When an osteotomy seems to be too invasive the arthroscopic release of the posterior oblique ligament might be an option. Patients with an intact contralateral chondral status, medium to slight malalignment who want to remain at high activity levels, remain good candidates for unloading osteotomies. Georg Thieme Verlag KG Stuttgart · New York.

  13. Replication-Coupled PCNA Unloading by the Elg1 Complex Occurs Genome-wide and Requires Okazaki Fragment Ligation

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    Takashi Kubota


    Full Text Available The sliding clamp PCNA is a crucial component of the DNA replication machinery. Timely PCNA loading and unloading are central for genome integrity and must be strictly coordinated with other DNA processing steps during replication. Here, we show that the S. cerevisiae Elg1 replication factor C-like complex (Elg1-RLC unloads PCNA genome-wide following Okazaki fragment ligation. In the absence of Elg1, PCNA is retained on chromosomes in the wake of replication forks, rather than at specific sites. Degradation of the Okazaki fragment ligase Cdc9 leads to PCNA accumulation on chromatin, similar to the accumulation caused by lack of Elg1. We demonstrate that Okazaki fragment ligation is the critical prerequisite for PCNA unloading, since Chlorella virus DNA ligase can substitute for Cdc9 in yeast and simultaneously promotes PCNA unloading. Our results suggest that Elg1-RLC acts as a general PCNA unloader and is dependent upon DNA ligation during chromosome replication.


    Directory of Open Access Journals (Sweden)

    D. S. Krivonosov


    Full Text Available Aim. To study effect of coronary revascularization in combination with inotropic stimulation and myocardial unloading on prognosis in elderly patients with myocardial infarction (MI complicated with heart failure (HF.Material and methods. 149 elderly patients with ECG picture of acute MI with ST segment elevation and HF symptoms were included into the study. All patients received standard therapy. According to the additional therapeutic maneuvers patients were split into four groups: 18 patients treated with percutaneous transluminal coronary angioplasty (PTCA combined with inotropic levosimendan (LS therapy; 20 patients with PTCA only; 22 patients treated with levosimendan (LS only; control group - 89 patients with standard therapy without PTCA or LS.Results. Combination of PTCA and LS in elderly patients with acute MI complicated by HF had advantages in comparison with PTCA or LS applied separately or not applied at all. Combined therapy with PTCA and LS resulted in more prominent improvement of left ventricle systolic function, increase in exercise tolerance and more effective prevention of cardiac remodeling and was safe.Conclusion. Combined therapy with PTCA and LS is more effective than separate usage of these methods in elderly patients with MI complicated with HF.

  15. Long-term monitoring of feral genetically modified herbicide-tolerant Brassica napus populations around unloading Japanese ports (United States)

    Katsuta, Kensuke; Matsuo, Kazuhito; Yoshimura, Yasuyuki; Ohsawa, Ryo


    Genetically modified, herbicide-tolerant (GMHT) Brassica napus plants originating from seed spill have recently been found along roadsides leading from Japanese ports that unload oilseed rape. Such introductions have potential biodiversity effects (as defined by the Cartagena Protocol): these include replacement of native elements in the biota through competitive suppression or hybridization. We conducted surveys in the period 2006–2011 to assess such threats. We examined shifts in the population distribution and occurrence of GMHT plants in 1,029 volunteer introduced assemblages of B. napus, 1,169 of B. juncea, and 184 of B. rapa around 12 ports. GMHT B. napus was found around 10 of 12 ports, but its proportion in the populations varied greatly by year and location. Over the survey period, the distributions of a pure non-GMHT population around Tobata and a pure GMHT population around Hakata increased significantly. However, there was no common trend of population expansion or contraction around the 12 ports. Furthermore, we found no herbicide tolerant B. juncea and B. rapa plants derived from crosses with GMHT B. napus. Therefore, GMHT B. napus is not invading native vegetation surrounding its populations and not likely to cross with congeners in Japanese environment. PMID:26175624

  16. Leg muscle activation during gait in Parkinson's disease: influence of body unloading. (United States)

    Dietz, V; Leenders, K L; Colombo, G


    The effect of body unloading (75, 50 and 25% of body weight) on upper and lower leg muscle activation during stepping on a treadmill was investigated in groups of patients with Parkinson's disease and age-matched healthy subjects. The aim of the study was to test the hypothesis that impaired extensor load receptor function exists in the patients. A strong load sensitivity was found for the gastrocnemius (GM) electromyographic (EMG) activity (i.e. EMG amplitude decreased with unloading during stepping in both groups of subjects). The change in the EMG amplitude of the rectus femoris was less dependent upon the load but was observed to be more pronounced in the patients. Upper and lower leg flexor muscles were relatively load-insensitive. The absolute GM EMG amplitude during the stance phase of stepping with normal body loading was significantly smaller in the patients than in the healthy subjects. It is suggested that the latter observation is due to a change in the threshold or bias of the extensor load reflex mechanism in the patients. The slope or gain of this reflex appears to be preserved.

  17. Altered cortical activation patterns associated with baroreflex unloading following 24 h of physical deconditioning. (United States)

    Shoemaker, J K; Usselman, C W; Rothwell, A; Wong, S W


    Cardiovascular arousal is associated with patterned cortical activity changes. Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control. The present study tested the hypothesis that HDBR deconditioning would modify the forebrain organization for heart rate (HR) control during baroreflex unloading. Heart rate variability (HRV), blood pressure and plasma hormones were analysed at rest, whereas HR and cortical autonomic activation patterns (functional magnetic resonance imaging) were measured during graded and randomly assigned lower body negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after (Post) a 24 h HDBR protocol (study 1; n = 8). An additional group was tested before and following diuretic-induced hypovolaemia (study 2; n = 9; spironolactone, 100 mg day(-1) for 3 days) that mimicked the plasma volume lost during HDBR (-15% in both studies; P physical deconditioning can induce rapid functional changes within the cortical circuitry associated with baroreflex unloading, changes that are distinct from diuretic-induced hypovolaemia. The results suggest that physical activity patterns exert a rapid and notable impact on the cortical circuitry associated with cardiovascular control.

  18. Use of loading-unloading compression curves in medical device design (United States)

    Ciornei, M. C.; Alaci, S.; Ciornei, F. C.; Romanu, I. C.


    The paper presents a method and experimental results regarding mechanical testing of soft materials. In order to characterize the mechanical behaviour of technological materials used in prosthesis, a large number of material constants are required, as well as the comparison to the original. The present paper proposes as methodology the comparison between compression loading-unloading curves corresponding to a soft biological tissue and to a synthetic material. To this purpose, a device was designed based on the principle of the dynamic harness test. A moving load is considered and the force upon the indenter is controlled for loading-unloading phases. The load and specimen deformation are simultaneously recorded. A significant contribution of this paper is the interpolation of experimental data by power law functions, a difficult task because of the instability of the system of equations to be optimized. Finding the interpolation function was simplified, from solving a system of transcendental equations to solving a unique equation. The characteristic parameters of the experimentally curves must be compared to the ones corresponding to actual tissue. The tests were performed for two cases: first, using a spherical punch, and second, for a flat-ended cylindrical punch.

  19. Early changes in costameric and mitochondrial protein expression with unloading are muscle specific. (United States)

    Flück, Martin; Li, Ruowei; Valdivieso, Paola; Linnehan, Richard M; Castells, Josiane; Tesch, Per; Gustafsson, Thomas


    We hypothesised that load-sensitive expression of costameric proteins, which hold the sarcomere in place and position the mitochondria, contributes to the early adaptations of antigravity muscle to unloading and would depend on muscle fibre composition and chymotrypsin activity of the proteasome. Biopsies were obtained from vastus lateralis (VL) and soleus (SOL) muscles of eight men before and after 3 days of unilateral lower limb suspension (ULLS) and subjected to fibre typing and measures for costameric (FAK and FRNK), mitochondrial (NDUFA9, SDHA, UQCRC1, UCP3, and ATP5A1), and MHCI protein and RNA content. Mean cross-sectional area (MCSA) of types I and II muscle fibres in VL and type I fibres in SOL demonstrated a trend for a reduction after ULLS (0.05 ≤ P muscle (P = 0.029). SOL muscle demonstrated a specific reduction in UCP3 content (-23%; P = 0.012). Muscle-specific effects of ULLS were identified for linear relationships between measured proteins, chymotrypsin activity and fibre MCSA. The molecular modifications in costamere turnover and energy homoeostasis identify that aspects of atrophy and fibre transformation are detectable at the protein level in weight-bearing muscles within 3 days of unloading.

  20. Early Changes in Costameric and Mitochondrial Protein Expression with Unloading Are Muscle Specific

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    Martin Flück


    Full Text Available We hypothesised that load-sensitive expression of costameric proteins, which hold the sarcomere in place and position the mitochondria, contributes to the early adaptations of antigravity muscle to unloading and would depend on muscle fibre composition and chymotrypsin activity of the proteasome. Biopsies were obtained from vastus lateralis (VL and soleus (SOL muscles of eight men before and after 3 days of unilateral lower limb suspension (ULLS and subjected to fibre typing and measures for costameric (FAK and FRNK, mitochondrial (NDUFA9, SDHA, UQCRC1, UCP3, and ATP5A1, and MHCI protein and RNA content. Mean cross-sectional area (MCSA of types I and II muscle fibres in VL and type I fibres in SOL demonstrated a trend for a reduction after ULLS (0.05≤P<0.10. FAK phosphorylation at tyrosine 397 showed a 20% reduction in VL muscle (P=0.029. SOL muscle demonstrated a specific reduction in UCP3 content (-23%; P = 0.012. Muscle-specific effects of ULLS were identified for linear relationships between measured proteins, chymotrypsin activity and fibre MCSA. The molecular modifications in costamere turnover and energy homoeostasis identify that aspects of atrophy and fibre transformation are detectable at the protein level in weight-bearing muscles within 3 days of unloading.

  1. Early Changes in Costameric and Mitochondrial Protein Expression with Unloading Are Muscle Specific (United States)

    Li, Ruowei; Linnehan, Richard M.; Castells, Josiane; Tesch, Per; Gustafsson, Thomas


    We hypothesised that load-sensitive expression of costameric proteins, which hold the sarcomere in place and position the mitochondria, contributes to the early adaptations of antigravity muscle to unloading and would depend on muscle fibre composition and chymotrypsin activity of the proteasome. Biopsies were obtained from vastus lateralis (VL) and soleus (SOL) muscles of eight men before and after 3 days of unilateral lower limb suspension (ULLS) and subjected to fibre typing and measures for costameric (FAK and FRNK), mitochondrial (NDUFA9, SDHA, UQCRC1, UCP3, and ATP5A1), and MHCI protein and RNA content. Mean cross-sectional area (MCSA) of types I and II muscle fibres in VL and type I fibres in SOL demonstrated a trend for a reduction after ULLS (0.05 ≤ P < 0.10). FAK phosphorylation at tyrosine 397 showed a 20% reduction in VL muscle (P = 0.029). SOL muscle demonstrated a specific reduction in UCP3 content (−23%; P = 0.012). Muscle-specific effects of ULLS were identified for linear relationships between measured proteins, chymotrypsin activity and fibre MCSA. The molecular modifications in costamere turnover and energy homoeostasis identify that aspects of atrophy and fibre transformation are detectable at the protein level in weight-bearing muscles within 3 days of unloading. PMID:25313365

  2. [Therapeutic effects and related mechanisms of erythropoietin sustained-release gelatin hydrogel microspheres on a murine model of hindlimb ischemia]. (United States)

    Xiao, J W; Li, L H; Hong, B Z; Xiao, J Q; Wei, D M; Jin, Z


    To investigate the therapeutic effects of erythropoietin sustained-release gelatin hydrogel microspheres (EPO-GHM) on a murine model of hindlimb ischemia and related mechanisms. Fifty two ten weeks old male C57BL/6J mice were assigned to 5 groups: sham-operated group (the right femoral artery suture was passed through the right femoral artery but not tied, n=8); saline group (right femoral artery ligation and intramuscular injection of saline at a dose of 4 ml/kg into the right hind limb, n=12); EPO group(right femoral artery ligation and intramuscular injection of EPO at a dose of 5 000 IU/kg into the right hind limb, n=12), empty GHM group (right femoral artery ligation and intramuscular injection of empty GHM at a dose of 4 ml/kg into the right hind limb, n=8); EPO-GHM group(right femoral artery ligation and intramuscular injection of EPO-GHM at a dose of 5 000 IU/kg into the right hind limb, n=12). The blood flow ratio of ischemic limb (right)/nonischemic limb (left) was measured using a laser Doppler perfusion imager. After 8 weeks, immunohistochemical analysis were used to evaluate the vessel density (vessel density of CD31 positive), arteriole density(vessel density of α-smooth muscle actin(α-SMA) positive) and muscle area(HHF35 positive area). The proliferating index of vessels was evaluated by double immunofluorescent labeling to evaluate effect of EPO-GHM on angiogenesis of ischemia limb. Western blot was used to evaluate the protein expression of EPO receptor, protein kinase B(AKT), p-AKT, endothelial nitric oxide synthase(eNOS), p-eNOS and matrix metalloproteinase 2(MMP-2). (1) Eight weeks later, the blood flow ratio of ischemic limb/nonischemic limb was significantly higher in the EPO-GHM group compared with other groups(0.810±0.080, 0.563±0.051, 0.570±0.056 and 0.561±0.052 respectively, all P0.05). (4)The proliferating index of vessels was higher in the EPO-GHM group compared with other groups(P0.05). RESULTS from present study suggest EPO

  3. Application of the simulation of a tank capacity proposal for loading and unloading process of bulk material

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    Janka Šaderová


    Full Text Available n this paper, the algorithm is given - how to design a tankfor bulk materials. An important part of the proposal is to setthe loading and unloading of a tank, which is also closely related to the proposal of its capacity and volume. Loading and unloadingprocess is dependent on several factors but the main are: method and speed of loading which represents the parameter - hour powerof loading device (e.g. continuous by a conveyor belt, method andspeed of unloading (continuousor at intervals and a typeand capacity of means of transport, in which the material loading (truck, rail car, conveyor belt system. The paper presents twomethods for determination of the loadingand unloading process - the graphic method and determination during the simulation -creating a simulation model.

  4. Locomotor loading mechanics in the hindlimbs of tegu lizards (Tupinambis merianae): comparative and evolutionary implications. (United States)

    Sheffield, K Megan; Butcher, Michael T; Shugart, S Katherine; Gander, Jennifer C; Blob, Richard W


    Skeletal elements are usually able to withstand several times their usual load before they yield, and this ratio is known as the bone's safety factor. Limited studies on amphibians and non-avian reptiles have shown that they have much higher limb bone safety factors than birds and mammals. It has been hypothesized that this difference is related to the difference in posture between upright birds and mammals and sprawling ectotherms; however, limb bone loading data from a wider range of sprawling species are needed in order to determine whether the higher safety factors seen in amphibians and non-avian reptiles are ancestral or derived conditions. Tegus (family Teiidae) are an ideal lineage with which to expand sampling of limb bone loading mechanics for sprawling taxa, particularly for lizards, because they are from a different clade than previously sampled iguanas and exhibit different foraging and locomotor habits (actively foraging carnivore versus burst-activity herbivore). We evaluated the mechanics of locomotor loading for the femur of the Argentine black and white tegu (Tupinambus merianae) using three-dimensional measurements of the ground reaction force and hindlimb kinematics, in vivo bone strains and femoral mechanical properties. Peak bending stresses experienced by the femur were low (tensile: 10.4 ± 1.1 MPa; compressive: -17.4 ± 0.9 MPa) and comparable to those in other reptiles, with moderate shear stresses and strains also present. Analyses of peak femoral stresses and strains led to estimated safety factor ranges of 8.8-18.6 in bending and 7.8-17.5 in torsion, both substantially higher than typical for birds and mammals but similar to other sprawling tetrapods. These results broaden the range of reptilian and amphibian taxa in which high femoral safety factors have been evaluated and further indicate a trend for the independent evolution of lower limb bone safety factors in endothermic taxa.

  5. Effects of Intermittent Weight-Bearing and Clenbuterol on Disuse Atrophy of Rat Hindlimb Muscles (United States)


    The present study was undertaken to evaluate the effects of intermittent weight-bearing (IWB) combined with β2-agonist clenbuterol (Cb) medication for suppressing muscle atrophy during progressive disuse atrophy. Male Wistar rats (age: 8weeks, body weight: 232 ± 14 g) were divided into a control group (CON) and an experimental group. The experimental group was further subdivided into a Cb medication group under normal conditions and a hindlimb unweighting (HU) treatment group. The HU treatment group was composed of four groups: HU treatment-only, HU treatment + IWB, HU treatment + Cb medication and HU treatment + IWB + Cb medication. IWB was performed by temporarily removing the suspension device for one hour daily. On Day 14, bilateral soleus muscle (SOL) and extensor digitorum longus muscle (EDL) were extracted. Muscles from the right side were used for the measurement of contractile properties (physiological functional evaluations). Muscles from the left side were used for histochemical and biochemical analysis. During HU, IWB combined with Cb medication worked to preserve the wet weight and relative weight of SOL as compared to CON. Its contractile properties were affected by weight-bearing, while the cross-sectional area of type I fiber and protein concentration were affected by Cb. This combined therapy had marked effects on the morphology of EDL, particularly on the cross-sectional area of type II fiber. The protein concentration and contractile properties of EDL were unaffected by this combined therapy. The effect of a combination of IWB and Cb medication was specific to fiber-type and region. The data suggested that 1) IWB was effective on functional aspects such as contractile properties and useful for physical therapy, 2) Cb medication exerted the atrophy-suppressive effect in morphological parameters and manifested less effect on functional aspects. The results in this study indicated the possibility of elevating the efficacy of IWB by Cb medication

  6. The phylogeny of the red panda (Ailurus fulgens): evidence from the hindlimb. (United States)

    Fisher, Rebecca E; Adrian, Brent; Elrod, Clay; Hicks, Michelle


    The red panda (Ailurus fulgens) is an endangered carnivore living in the temperate forests of the Himalayas and southern China. The phylogeny of the red panda has been the subject of much debate. Morphological and molecular studies have supported a wide range of possible relationships, including close ties to procyonids, ursids, mustelids, and mephitids. This study provides additional morphological data, including muscle maps, for Ailurus. The hindlimbs of four cadavers from the National Zoological Park were dissected. Red pandas retain a number of muscles lost in other carnivore groups, including muscles and tendons related to their robust and weight-bearing hallux. Three features, including a single-bellied m. sartorius, a proximal insertion for m. abductor digiti V, and an absent m. articularis coxae, are found in all terrestrial arctoids, including Ailurus. In addition, red pandas are similar to ursids and canids in lacking a caudal belly of m. semitendinosus, while they resemble procyonids and mustelids in the degree of fusion observed between mm. gluteus medius and piriformis. Furthermore, Ailurus and procyonids are characterized by numerous subdivisions within the adductor compartment, while red pandas and raccoons share a variable m. semimembranosus, composed of one, two, or three bellies. Lastly, a deep plantar muscle inserting onto the metatarsophalangeal joint of the hallux is described for Ailurus. This muscle has not been previously described and is given the name m. flexor hallucis profundus. Additional dissections of the forelimb and axial musculature of red pandas may shed further light on the phylogeny of this species. In addition, the muscle maps presented here offer a valuable resource for interpreting the functional anatomy of fossil ailurids.

  7. Tendon material properties vary and are interdependent among turkey hindlimb muscles (United States)

    Matson, Andrew; Konow, Nicolai; Miller, Samuel; Konow, Pernille P.; Roberts, Thomas J.


    SUMMARY The material properties of a tendon affect its ability to store and return elastic energy, resist damage, provide mechanical feedback and amplify or attenuate muscle power. While the structural properties of a tendon are known to respond to a variety of stimuli, the extent to which material properties vary among individual muscles remains unclear. We studied the tendons of six different muscles in the hindlimb of Eastern wild turkeys to determine whether there was variation in elastic modulus, ultimate tensile strength and resilience. A hydraulic testing machine was used to measure tendon force during quasi-static lengthening, and a stress–strain curve was constructed. There was substantial variation in tendon material properties among different muscles. Average elastic modulus differed significantly between some tendons, and values for the six different tendons varied nearly twofold, from 829±140 to 1479±106 MPa. Tendons were stretched to failure, and the stress at failure, or ultimate tensile stress, was taken as a lower-limit estimate of tendon strength. Breaking tests for four of the tendons revealed significant variation in ultimate tensile stress, ranging from 66.83±14.34 to 112.37±9.39 MPa. Resilience, or the fraction of energy returned in cyclic length changes was generally high, and one of the four tendons tested was significantly different in resilience from the other tendons (range: 90.65±0.83 to 94.02±0.71%). An analysis of correlation between material properties revealed a positive relationship between ultimate tensile strength and elastic modulus (r2=0.79). Specifically, stiffer tendons were stronger, and we suggest that this correlation results from a constrained value of breaking strain, which did not vary significantly among tendons. This finding suggests an interdependence of material properties that may have a structural basis and may explain some adaptive responses observed in studies of tendon plasticity. PMID:22771746

  8. Investigating tendon mineralisation in the avian hindlimb: a model for tendon ageing, injury and disease (United States)

    Agabalyan, Natacha A; Evans, Darrell J R; Stanley, Rachael L


    Mineralisation of the tendon tissue has been described in various models of injury, ageing and disease. Often resulting in painful and debilitating conditions, the processes underlying this mechanism are poorly understood. To elucidate the progression from healthy tendon to mineralised tendon, an appropriate model is required. In this study, we describe the spontaneous and non-pathological ossification and calcification of tendons of the hindlimb of the domestic chicken (Gallus gallus domesticus). The appearance of the ossified avian tendon has been described previously, although there have been no studies investigating the developmental processes and underlying mechanisms leading to the ossified avian tendon. The tissue and cells from three tendons – the ossifying extensor and flexor digitorum longus tendons and the non-ossifying Achilles tendon – were analysed for markers of ageing and mineralisation using histology, immunohistochemistry, cytochemistry and molecular analysis. Histologically, the adult tissue showed a loss of healthy tendon crimp morphology as well as markers of calcium deposits and mineralisation. The tissue showed a lowered expression of collagens inherent to the tendon extracellular matrix and presented proteins expressed by bone. The cells from the ossified tendons showed a chondrogenic and osteogenic phenotype as well as tenogenic phenotype and expressed the same markers of ossification and calcification as the tissue. A molecular analysis of the gene expression of the cells confirmed these results. Tendon ossification within the ossified avian tendon seems to be the result of an endochondral process driven by its cells, although the roles of the different cell populations have yet to be elucidated. Understanding the role of the tenocyte within this tissue and the process behind tendon ossification may help us prevent or treat ossification that occurs in injured, ageing or diseased tendon. PMID:23826786

  9. Topography of spinal neurons active during hindlimb withdrawal reflexes in the decerebrate cat. (United States)

    Gustafson, K J; Moffitt, M A; Wang, X; Sun, J; Snyder, S; Grill, W M


    There exists a spatial organization of receptive fields and a modular organization of the flexion withdrawal reflex system. However, the three dimensional location and organization of interneurons interposed in flexion reflex pathways has not been systematically examined. We determined the anatomical locations of spinal neurons involved in the hindlimb flexion withdrawal reflex using expression of the immediate early gene c-fos and the corresponding FOS protein. The flexion withdrawal reflex was evoked in decerebrate cats via stimulation of the tibial or superficial peroneal nerve. Animals that received stimulation had significantly larger numbers of cells expressing FOS-like immunoreactivity (42.7+/-2.3 cells/section, mean+/-standard error of the mean) than operated unstimulated controls (18.6+/-1.4 cells/section). Compared with controls, cells expressing FOS-like immunoreactivity were located predominantly on the ipsilateral side, in laminae IV-VI, at L6 and rostral L7 segments, and between 20% and 60% of the distance from the midline to the lateral border of the ventral gray matter. Labeled neurons resulting from tibial nerve stimulation were medial to neurons labeled following superficial peroneal nerve stimulation in laminae I-VI, but not VII. The mean mediolateral positions of labeled neurons from both nerves shifted medially as the transverse plane in which they were viewed was moved from rostral to caudal and as the coronal plane in which they were viewed was moved from dorsal to ventral. The mediolateral separation between populations of labeled cells was consistent with primary afferent projections and the location of reflex encoders. This topographical segregation corresponding to different afferent inputs is a possible anatomical substrate for a modular organization of the flexion withdrawal reflex system.

  10. Heterogenic feedback between hindlimb extensors in the spontaneously locomoting premammillary cat. (United States)

    Ross, Kyla T; Nichols, T Richard


    Electrophysiological studies in anesthetized animals have revealed that pathways carrying force information from Golgi tendon organs in antigravity muscles mediate widespread inhibition among other antigravity muscles in the feline hindlimb. More recent evidence in paralyzed or nonparalyzed decerebrate cats has shown that some inhibitory pathways are suppressed and separate excitatory pathways from Golgi tendon organ afferents are opened on the transition from steady force production to locomotor activity. To obtain additional insight into the functions of these pathways during locomotion, we investigated the distribution of force-dependent inhibition and excitation during spontaneous locomotion and during constant force exertion in the premammillary decerebrate cat. We used four servo-controlled stretching devices to apply controlled stretches in various combinations to the gastrocnemius muscles (G), plantaris muscle (PLAN), flexor hallucis longus muscle (FHL), and quadriceps muscles (QUADS) during treadmill stepping and the crossed-extension reflex (XER). We recorded the force responses from the same muscles and were therefore able to evaluate autogenic (intramuscular) and heterogenic (intermuscular) reflexes among this set of muscles. In previous studies using the intercollicular decerebrate cat, heterogenic inhibition among QUADS, G, FHL, and PLAN was bidirectional. During treadmill stepping, heterogenic feedback from QUADS onto G and G onto PLAN and FHL remained inhibitory and was force-dependent. However, heterogenic inhibition from PLAN and FHL onto G, and from G onto QUADS, was weaker than during the XER. We propose that pathways mediating heterogenic inhibition may remain inhibitory under some forms of locomotion on a level surface but that the strengths of these pathways change to result in a proximal to distal gradient of inhibition. The potential contributions of heterogenic inhibition to interjoint coordination and limb stability are discussed.

  11. Hindlimb muscle anatomical mechanical advantage differs among joints and stride phases in basilisk lizards. (United States)

    Bergmann, Philip J; Hare-Drubka, Meredith


    The vertebrate musculoskeletal system is composed of skeletal levers powered by muscles. Effective mechanical advantage (EMA) and muscle properties influence organismal performance at various tasks. Anatomical mechanical advantage (AMA) is a proxy for EMA that facilitates the study of preserved specimens when many muscles or many species are of interest. AMA is the quotient of in-lever to out-lever length, and quantifies the force-velocity trade-off of a lever, where high AMAs translate into high force, low velocity levers. We studied AMAs, physiological cross-sectional areas (PCSAs), fiber lengths, and fiber widths for 20 hindlimb muscles of the lizard Basiliscus vittatus, moving the hip, knee, and ankle during both the stance and swing phases of the stride. We tested the hypotheses that muscles moving proximal limb joints, and those active during stance, would have characteristics that maximize force. We also tested whether adults had more force-optimized levers than juveniles to compensate for higher body mass. We found no differences between adults and juveniles, but found differences among joints and between stride phases. AMAs were lowest and PCSAs highest for the knee, and PCSA was higher for stance than swing muscles. Fiber width decreased distally, but did not differ between stride phases. Fiber length of stance muscles decreased distally and was highest for swing muscles of the knee. Our findings show that different muscle and lever characteristics allow the knee to be both force- and velocity-optimized, indicating its important role in locomotion. Copyright © 2015 Elsevier GmbH. All rights reserved.

  12. Adipose-derived stem cell spheroid treated with low-level light irradiation accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia. (United States)

    Park, In-Su; Chung, Phil-Sang; Ahn, Jin Chul


    We investigated whether low-level light irradiation (LLLI) before adipose-derived stromal cells (ASCs) spheroid transplantation improved hind-limb functional recovery by stimulation of angiogenesis. The spheroid, composed of ASCs, was irradiated with low-level light and expressed angiogenic factors, including vascular endothelial growth factor and basic fibroblast growth factor. From immunochemical staining analysis, the spheroid of ASCs included CD31+, KDR+ and CD34+, whereas monolayer-cultured ASCs were negative for these markers. To evaluate the therapeutic effect of the ASC spheroid treated with LLLI in vivo, phosphate-buffered saline, monolayer ASCs, LLLI-monolayer ASCs, spheroid ASCs and LLLI-spheroid ASCs were transplanted into a hind-limb ischemia model. The LLLI-spheroid ASCs transplanted into the hind-limb ischemia differentiated into endothelial cells and remained differentiated. Transplantation of LLLI-spheroid ASCs into the hind-limb ischemia significantly elevated the density of vascular formations through angiogenic factors released by the ASCs and enhanced tissue regeneration at the lesion site. Consistent with these results, the transplantation of LLLI-spheroid ASCs significantly improved functional recovery compared with ASC or spheroid ASC transplantation and PBS treatment. These findings suggest that transplantation of ASC spheroid treated with LLLI may be an effective stem cell therapy for the treatment of hind-limb ischemia and peripheral vascular disease. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. An in Vitro Study on Tissue Repair: Impact of Unloading on Cells Involved in the Remodelling Phase (United States)

    Monici, Monica; Cialdai, Francesca; Romano, Giovanni; Fusi, Franco; Egli, Marcel; Pezzatini, Silvia; Morbidelli, Lucia


    The number of astronauts involved in long-lasting missions and extra-vehicular activities is going to increase in the future. Consequently, the chance of injury due to traumatic events or unexpected emergency surgery will also increase and medical evacuation times to earth will be prolonged. Hence, the need to address requirements for surgery and trauma care in non terrestrial environments will be a priority. Tissue repair in weightlessness should therefore be regarded as a major issue not enough studied to date. Wound healing is a complex multi-step process, crucial to the survival of the organism. It starts with an inflammatory phase followed by a remodelling phase. During repair, the extracellular matrix (ECM) is sequentially remodelled by the concerted action of different cell types, in order to rebuild a functional tissue. The available literature concerning wound healing with mechanical unloading presents controversial results. However, many studies indicate impairment of the healing processes. Here we present a study on the behaviour of cells involved in the remodelling phase of repair, e.g. fibroblasts and endothelial cells, in response to microgravity ( μg). In particular, their adhesion/migration, cytoskeleton organization, production of ECM molecules and receptors have been investigated. Cell response to pulsed Nd: YAG laser irradiation has also been investigated in order to evaluate the possibility to use laser irradiation for counteracting the effect of μg on wound healing. In μg, we observed alterations in production/assembling of ECM molecules. Increased fibronectin (FN) and laminin (LM) could be the cause for impaired ECM rebuilding and altered cell adhesion/migration. Treatment with Nd:YAG laser pulses induced organized fibrillogenesis and favoured endothelial cell spreading and monolayer formation. These findings open the way for a better understanding of tissue repair mechanisms in space and future clinical applications on earth.

  14. The effects of exogenous crosslinking on hydration and fluid flow in the intervertebral disc subjected to compressive creep loading and unloading. (United States)

    Chuang, Shih-Youeng; Popovich, John M; Lin, Leou-Chyr; Hedman, Thomas P


    In vitro study of genipin crosslinking effect on disc water content changes under compressive loading and unloading. To investigate the influence of collagen crosslinking on hydration and fluid flow in different regions of intact discs, and to evaluate the nutritional implications. Age-related reductions of nutrient supply and waste product removal are critically important factors in disc pathogenesis. Diffusion and fluid flow are blocked by subchondral bone thickening, cartilaginous endplate calcification, loss of hydrophilic proteoglycans, and clogging of anular pores by degraded matrix molecules. Previous studies demonstrated increased hydraulic permeability and macromolecular transport through crosslinked collagenous matrices. Genipin has also demonstrated the capability to increase retention of proteoglycans. A total of 57 bovine lumbar motion segments were divided randomly into phosphate buffered saline and 0.33% genipin-soaked treatment groups. Water content changes were measured using a mass-loss technique in 3 intervertebral disc regions following successive stages of compressive loading and unloading (post-treatment, after 1 hour 750 N compression, and after a subsequent 24-hour period of nominal loading). Net flow of fluid into or out of a region was determined from the percentage change in mean water content from successive groups. Fluid flow to and from the nucleus doubled with genipin crosslinking. Relative to the buffer-only controls, overall net fluid flow increased 103% in the nucleus pulposus, 36% in the inner anulus, and was 31% less in the outer anulus of genipin treated discs. The effects of genipin crosslinking on matrix permeability and proteoglycan retention can alter hydration levels and fluid flow in the intervertebral disc. Resulting increases in fluid flow, including a doubling of flow to and from the nucleus, could lead to enhanced nutritional inflow and waste product outflow for the disc, and may have implications for emerging cell

  15. Modulation of spontaneous locomotor and respiratory drives to hindlimb motoneurons temporally related to sympathetic drives as revealed by Mayer waves

    Directory of Open Access Journals (Sweden)

    Katinka eStecina


    Full Text Available In this study we investigated how the networks mediating respiratory and locomotor drives to lumbar motoneurons interact and how this interaction is modulated in relation to periodic variations in blood pressure (Mayer waves. Seven decerebrate cats, under neuromuscular blockade, were used to study central respiratory drive potentials (CRDPs, usually enhanced by added CO2 and spontaneously occurring locomotor drive potentials (LDPs in hindlimb motoneurons, together with hindlimb and phrenic nerve discharges. In four of the cats both drives and their voltage-dependent amplification were absent or modest, but in the other three, one or other of these drives was common and the voltage-dependent amplification was frequently strong. Moreover, in these three cats the blood pressure showed marked periodic variation (Mayer waves, with a slow rate (periods 9 - 104 s, mean 39 ± 17 SD. Profound modulation, synchronized with the Mayer waves was seen in the occurrence and/or in the amplification of the CRDPs or LDPs. In one animal, where CRDPs were present in most cells and the amplification was strong, the CRDP consistently triggered sustained plateaux at one phase of the Mayer wave cycle. In the other two animals, LDPs were common, and the occurrence of the locomotor drive was gated by the Mayer wave cycle, sometimes in alternation with the respiratory drive. Other interactions between the two drives involved respiration providing leading events, including co-activation of flexors and extensors during post-inspiration or a locomotor drive gated or sometimes entrained by respiration. We conclude that the respiratory drive in hindlimb motoneurons is transmitted via elements of the locomotor central pattern generator. The rapid modulation related to Mayer waves suggests the existence of a more direct and specific descending modulatory control than has previously been demonstrated.

  16. A 3D map of the hindlimb motor representation in the lumbar spinal cord in Sprague Dawley rats (United States)

    Borrell, Jordan A.; Frost, Shawn B.; Peterson, Jeremy; Nudo, Randolph J.


    Objective. Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Approach. Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a 3D (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and electromyographic (EMG) activity. Via fine wire EMG electrodes, stimulus-triggered averaging (StTA) was used on rectified EMG data to determine response latency. Main results. Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. Significance. The derived motor map provides insight into the parameters needed for future neuromodulatory devices.

  17. An experimental study and mathematical simulation of adrenergic control of hindlimb vessels in rats after 3-week tail suspension

    DEFF Research Database (Denmark)

    Rodionov, Ivan M; Timin, Eugeny N; Matchkov, Vladimir


    Adrenoreactivity of rat hindlimb vessels was studied in experiments with constant-pressure saline perfusion. An original mathematical model was applied to evaluate the mechanism of changes in vascular tone regulation. A 3-week suspension resulted in decreased responses to sympathetic nerve...... stimulation, as well as to exogenous noradrenaline, the latter effect being registered when the pressure level was close to normal. Mathematical simulation indicated that long-term suspension induces both structural and functional changes in the vascular bed of the hind limbs, one of which is a disorder...

  18. Sudden drop in ground support produces force-related unload response in human overground walking

    DEFF Research Database (Denmark)

    Af Klint, Richard; Nielsen, Jens Bo; Sinkjaer, Thomas


    healthy volunteers. Subjects walked unrestrained over a hydraulically actuated platform. On random trials the platform was accelerated downward at 0.8 g, unloading the plantar flexor muscles in midstance or late stance. The drop of the platform resulted in a significant depression of the soleus muscle...... was decreased starting 22 ms (SD 15) after the drop. To investigate the role of length- and velocity-sensitive afferents on the depression in soleus muscle activity, the ankle rotation was arrested by using an ankle foot orthotic as the platform was dropped. Preventing the ankle movement did not significantly......Humans maneuver easily over uneven terrain. To maintain smooth and efficient gait the motor system needs to adapt the locomotor output to the walking environment. In the present study we investigate the role of sensory feedback in adjusting the soleus muscle activity during overground walking in 19...

  19. Assessing Viscoelastic Properties of Polydimethylsiloxane (PDMS) Using Loading and Unloading of the Macroscopic Compression Test (United States)

    Fincan, Mustafa

    Polydimethylsiloxane (PDMS) mechanical properties were measured using custom-built compression test device. PDMS elastic modulus can be varied with the elastomer base to the curing agent ratio, i.e. by changing the cross-linking density. PDMS samples with different crosslink density in terms of their elastic modulus were measured. In this project the PDMS samples with the base/curing agent ratio ranging from 5:1 to 20:1 were tested. The elastic modulus varied with the amount of the crosslinker, and ranged from 0.8 MPa to 4.44 MPa. The compression device was modified by adding digital displacement gauges to measure the lateral strain of the sample, which allowed obtaining the true stress-strain data. Since the unloading behavior was different than the loading behavior of the viscoelastic PDMS, it was utilized to asses viscoelastic properties of the polymer. The thesis describes a simple method for measuring mechanical properties of soft polymeric materials.


    Directory of Open Access Journals (Sweden)

    Dorota Janiszewska


    Full Text Available In this study characterization of sensory and physical-chemical properties of representative samples of technological waste water after hydraulic unloading fish from fishing vessels, including fishing boats equipped with RSW (Refrigerated Sea Water System or CSW (Chilling Sea Water System system was described. Sensory quality and analytical determinations in technological waste water samples was analyzed. They demonstrated that their sensory quality attributes and physical-chemical properties were different and depending on the destination of fish caught (consumption or industrial fishing, contact time-caught fish with seawater and water temperature (winter or summer season. Because technological waste water has a lot of substance content of protein, fat, nitrogen, phosphorus and chlorine compounds it is a threat to the natural environment. In connection with such a broad problem of utilization of technological waste water from fishing boats for Baltic fish is one of the most important issues to solve for fishermen and environmentalists.

  1. Spatio-temporal gait characteristics of the hind-limb cycles during voluntary bipedal and quadrupedal walking in bonobos (Pan paniscus). (United States)

    Aerts, P; Van Damme, R; Van Elsacker, L; Duchêne, V


    Spatio-temporal gait characteristics (step and stride length, stride frequency, duty factor) were determined for the hind-limb cycles of nine bonobos (Pan paniscus) walking quadrupedally and bipedally at a range of speeds. The data were recalculated to dimensionless quantities according to the principle of dynamic similarity. Lower leg length was used as the reference length. Interindividual variability in speed modulation strategy of bonobos appears to be low. Compared to quadrupedal walking, bipedal bonobos use smaller steps to attain a given speed (differences increase with speed), resulting in shorter strides at a higher frequency. In the context of the ("hybrid") dynamic pattern approach to locomotion (Latach, 1998) we argue that, despite these absolute differences, intended walking speed is the basic control variable which elicits both quadrupedal and bipedal walking kinematics in a similar way. Differences in the initial status of the dynamic system may be responsible for the differences in step length between both gaits. Comparison with data deduced from the literature shows that the effects of walking speed on stride length and frequency are similar in bonobos, common chimpanzees, and humans. This suggests that (at least) within extant homininae, spatio-temporal gait characteristics are highly comparable, and this in spite of obvious differences in mass distribution and bipedal posture. Copyright 2000 Wiley-Liss, Inc.

  2. Adipose-Derived Stem Cells and Vascularized Lymph Node Transfers Successfully Treat Mouse Hindlimb Secondary Lymphedema by Early Reconnection of the Lymphatic System and Lymphangiogenesis. (United States)

    Hayashida, Kenji; Yoshida, Shuhei; Yoshimoto, Hiroshi; Fujioka, Masaki; Saijo, Hiroto; Migita, Kiyoshi; Kumaya, Misato; Akita, Sadanori


    Secondary lymphedema is often observed in postmalignancy treatment of the breast and the gynecologic organs, but effective therapies have not been established in chronic cases even with advanced physiologic operations. Currently, reconstructive surgery with novel approaches has been attempted. The hindlimbs of 10-week-old male C57BL/6J mice, after 30-Gy x-irradiation, surgical lymph node dissection, and 5-mm gap creation, were divided into four groups, with vascularized lymph node transfer abdominal flap and 1.0 × 10 adipose-derived stem cells. Lymphatic flow assessment, a water-displacement plethysmometer paw volumetry test, tissue quantification of lymphatic vessels, and functional analysis of lymphatic vessels and nodes were performed. Photodynamic Eye images, using indocyanine green fluorescence, demonstrated immediate staining in subiliac lymph nodes, and linear pattern imaging of the proximal region was observed with the combined treatment of adipose-derived stem cells and vascularized lymph node transfer. Both percentage improvement and percentage deterioration with the combined treatment of adipose-derived stem cells and vascularized lymph node transfer were significantly better than with other treatments (p lymphatic vessels with LYVE-1 immunoreactivity significantly increased in mice treated with adipose-derived stem cells (p lymphatic vessels and vascularized lymph node transfers induce the lymphatic flow drainage to the circulatory system. Combined adipose-derived stem cell and vascularized lymph node transfer treatment in secondary lymphedema may effectively decrease edema volume and restore lymphatic function by lymphangiogenesis and the lymphatic-to-venous circulation route.

  3. Long-term results of an unloader brace in patients with unicompartmental knee osteoarthritis. (United States)

    Wilson, Becky; Rankin, Heather; Barnes, C Lowry


    Previously, we reported a prospective study of 30 patients with unicompartmental osteoarthritis of the knee treated nonoperatively with an unloader brace and average follow-up of 2.7 years. Although the initial study suggested short-term benefit according to pain and function measures, the objective of the current study was to evaluate these same patients via telephone questionnaire to determine the status of their brace use and any surgical procedures on the affected limb. Because we noted that even at 2.7 years, some patients opted for surgical management despite good response to bracing, our hypothesis was that these patients would not opt for long-term brace wear. Twenty-four of 30 patients were available for reporting based on telephone interview; in addition, we talked with family members of 5 patients who had died. When evaluated at 2.7 years, 41% of the 30 patients were still using the brace, 35% had discontinued brace use, and 24% had undergone arthroplasty. When contacted for the follow-up survey at an average of 11.2 years, 17 (58.6%) of the 29 patients had undergone arthroplasty. The mean interval between initial evaluation and arthroplasty was 3.9 years. In addition, 7 patients had undergone arthroscopic surgery. Importantly, none of the patients were still wearing the brace. The use of an unloader brace is effective in providing short-term pain relief and improved function; however, most patients subsequently opt for total knee replacement on the symptomatic knee. Copyright 2011, SLACK Incorporated.

  4. The nonlinear unloading behavior of a typical Ni-based superalloy during hot deformation: a unified elasto-viscoplastic constitutive model (United States)

    Chen, Ming-Song; Lin, Y. C.; Li, Kuo-Kuo; Chen, Jian


    In authors' previous work (Chen et al. in Appl Phys A. doi: 10.1007/s00339-016-0371-6, 2016), the nonlinear unloading behavior of a typical Ni-based superalloy was investigated by hot compressive experiments with intermediate unloading-reloading cycles. The characters of unloading curves were discussed in detail, and a new elasto-viscoplastic constitutive model was proposed to describe the nonlinear unloading behavior of the studied Ni-based superalloy. Still, the functional relationships between the deformation temperature, strain rate, pre-strain and the parameters of the proposed constitutive model need to be established. In this study, the effects of deformation temperature, strain rate and pre-strain on the parameters of the new constitutive model proposed in authors' previous work (Chen et al. 2016) are analyzed, and a unified elasto-viscoplastic constitutive model is proposed to predict the unloading behavior at arbitrary deformation temperature, strain rate and pre-strain.

  5. 40 CFR Table 2 to Subpart Cccccc... - Applicability Criteria and Management Practices for Gasoline Cargo Tanks Unloading at Gasoline... (United States)


    ... Practices for Gasoline Cargo Tanks Unloading at Gasoline Dispensing Facilities With Monthly Throughput of 100,000 Gallons of Gasoline or More 2 Table 2 to Subpart CCCCCC of Part 63 Protection of Environment... Pollutants for Source Category: Gasoline Dispensing Facilities Pt. 63, Subpt. CCCCCC, Table 2 Table 2 to...

  6. 9 CFR 325.17 - Loading or unloading products in sealed railroad cars, trucks, etc., en route prohibited; exception. (United States)


    ... sealed railroad cars, trucks, etc., en route prohibited; exception. 325.17 Section 325.17 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND... TRANSPORTATION § 325.17 Loading or unloading products in sealed railroad cars, trucks, etc., en route prohibited...

  7. Respiratory muscle activity and patient–ventilator asynchrony during different settings of noninvasive ventilation in stable hypercapnic COPD: does high inspiratory pressure lead to respiratory muscle unloading?

    Directory of Open Access Journals (Sweden)

    Duiverman ML


    Full Text Available Marieke L Duiverman,1 Anouk S Huberts,2 Leo A van Eykern,3 Gerrie Bladder,1 Peter J Wijkstra1 1Department of Pulmonary Diseases and Home Mechanical Ventilation, University Medical Centre Groningen, 2Faculty of Medical Sciences, University of Groningen, 3Inbiolab B.V., Groningen, the Netherlands Introduction: High-intensity noninvasive ventilation (NIV has been shown to improve outcomes in stable chronic obstructive pulmonary disease patients. However, there is insufficient knowledge about whether with this more controlled ventilatory mode optimal respiratory muscle unloading is provided without an increase in patient–ventilator asynchrony (PVA. Patients and methods: Ten chronic obstructive pulmonary disease patients on home mechanical ventilation were included. Four different ventilatory settings were investigated in each patient in random order, each for 15 min, varying the inspiratory positive airway pressure and backup breathing frequency. With surface electromyography (EMG, activities of the intercostal muscles, diaphragm, and scalene muscles were determined. Furthermore, pressure tracings were derived simultaneously in order to assess PVA. Results: Compared to spontaneous breathing, the most pronounced decrease in EMG activity was achieved with the high-pressure settings. Adding a high breathing frequency did reduce EMG activity per breath, while the decrease in EMG activity over 1 min was comparable with the high-pressure, low-frequency setting. With high backup breathing frequencies less breaths were pressure supported (25% vs 97%. PVAs occurred more frequently with the low-frequency settings (P=0.017. Conclusion: High-intensity NIV might provide optimal unloading of respiratory muscles, without undue increases in PVA. Keywords: electromyography, high-intensity NIV, chronic obstructive pulmonary disease, ineffective efforts

  8. Angiopoietin-2 impairs collateral artery growth associated with the suppression of the infiltration of macrophages in mouse hindlimb ischaemia

    Directory of Open Access Journals (Sweden)

    Xiaoyong Tan


    Full Text Available Abstract Background Angiopoietin-2 (Ang-2, a ligand of the Tie-2 receptor, plays an important role in maintaining endothelial cells and in destabilizing blood vessels. Collateral artery growth (arteriogenesis is a key adaptive response to arterial occlusion. It is unknown whether the destabilization of blood vessels by Ang-2 can affect arteriogenesis and modulate mononuclear cell function. This study aimed to investigate the effects of Ang-2 on collateral artery growth. Methods Hindlimb ischaemia model was produced in C57BL/6 mice by femoral artery ligation. Blood flow perfusion was measured using a laser Doppler perfusion imager quantitative RT-PCR analysis was applied to identify the level of angiogenic factors. Results After the induction of hindlimb ischaemia, blood flow recovery was impaired in mice treated with recombinant Ang-2 protein; this was accompanied by a reduction of peri-collateral macrophage infiltration. In addition, quantitative RT-PCR analysis revealed that Ang-2 treatment decreased monocyte chemotactic protein-1 (MCP-1, platelet-derived growth factor-BB (PDGF-BB mRNA levels in ischaemic adductor muscles. Ang-2 can lead to macrophage M1/M2 polarization shift inhibition in the ischaemic muscles. Furthermore, Ang-2 reduced the in vitro inflammatory response in macrophages and vascular cells involved in arteriogenesis. Conclusions Our results demonstrate that Ang-2 is essential for efficient arteriogenesis, which controls macrophage infiltration.

  9. Comparative functional anatomy of hindlimb muscles and bones with reference to aquatic adaptation of the sea otter. (United States)

    Mori, Kent; Suzuki, Satoshi; Koyabu, Daisuke; Kimura, Junpei; Han, Sung-Yong; Endo, Hideki


    Although the sea otter (Enhydra lutris) is a complete aquatic species, spending its entire life in the ocean, it has been considered morphologically to be a semi-aquatic animal. This study aimed to clarify the unique hindlimb morphology and functional adaptations of E. lutris in comparison to other Mustelidae species. We compared muscle mass and bone measurements of five Mustelidae species: the sea otter, Eurasian river otter (Lutra lutra), American mink (Neovison vison), Japanese weasel (Mustela itatsi) and Siberian weasel (M. sibirica). In comparison with the other 4 species, E. lutris possessed significantly larger gluteus, popliteus and peroneus muscles, but smaller adductor and ischiopubic muscles. The popliteus muscle may act as a medial rotator of the crus, and the peroneus muscle may act as an abductor of the fifth toe and/or the pronator of the foot. The bundles of the gluteus superficialis muscle of E. lutris were fused with those of the tensor fasciae latae muscle and gluteofemoralis muscles, and they may play a role in femur abduction. These results suggest that E. lutris uses the abducted femur, medially rotated crus, eversion of the ankle and abducted fifth digit or extended interdigital web as a powerful propulsion generator. Therefore, we conclude that E. lutris is a complete aquatic animal, possessing differences in the proportions of the hindlimb muscles compared with those in other semi-aquatic and terrestrial mustelids.

  10. Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice. (United States)

    Brooks, Matthew J; Hajira, Ameena; Mohamed, Junaith S; Alway, Stephen E


    Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a non-damaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice (n=6/group) were randomly placed into 5 groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: non-suspended mice-cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation, was evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force and decreased the in vivo fatigability and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type type I and IIa MHC abundance, increased fiber cross sectional area (CSA), and an increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7 positive nuclei inside muscle fibers and a greater MyoD to Pax 7 protein ratio when compared to HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR had lower levels of the inactive phosphorylated YAP serine127 which may have contributed to increased satellite cell activation creased with reloading after HSU. These results indicate that voluntary wheel running increased YAP

  11. Effects of Hind Limb Unloading on Pharmacokinetics of Procainamide in Mice (United States)

    Risin, Semyon A.; Dasgupta, Amitava; Ramesh, Govindarajan T.; Risin, Diana


    The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in space. It is prudent to expect that low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration. Among the medications of special interest are the cardiovascular drugs, especially the antiarrhythmic agents. In this study we used hind limb unloaded (HLU) mice as a model to investigate possible changes in the PK of a common antiarrhythmic drug procainamide (PA). Prior to drug administration the experimental animals were tail suspended for 24 hours and the control animals were kept free. PA (150-250 mg per kg) was given orally by a gavage procedure. After that the experimental mice were kept suspended for additional 1, 2, 3 and 6 hours. At these time points the serum concentration of PA and N-acetyl-procainamide (NAPA), an active metabolite which is formed by N-acetyltransferase in the liver, were measured by the fluorescence polarization immunoassay (FPIA) on the AxSYM autoanalyzer (Abbott Laboratories, Abbott Park, IL). The serum level of PA in HLU mice at 1 hour after administration was almost 40% lower than in controls. At 2-3 hours the difference still maintained, however, it was not statistically significant; at 6 hours no difference was detected. The level of NAPA in HLU mice was slightly lower at 1 and 2 hours but the difference did not reach statistical significance. The estimated PA half-life time in HLU mice was almost 55% longer than in control animals. These results confirm that hind limb unloading and related hemodynamic changes significantly alter the PK of PA. The effects are most likely primarily associated with a decrease in the drug absorption, especially within the first two hours after administration. At the same time prolongation of the PA half

  12. A pressure plate study on fore and hindlimb loading and the association with hoof contact area in sound ponies at the walk and trot. (United States)

    Oosterlinck, M; Pille, F; Back, W; Dewulf, J; Gasthuys, F


    The aim of this study was to evaluate the association between fore- and hind-hoof contact area and limb loading. Data from a previous study on forelimb loading and symmetry were compared with data on hindlimb kinetics, and the fore- and hind-hoof contact area at the walk and trot was evaluated. Five sound ponies, selected for symmetrical feet, were walked and trotted over a pressure plate embedded in a custom-made runway. The hindlimb peak vertical force (PVF) and vertical impulse (VI) were found to be significantly lower than in the forelimb, whereas their high symmetry ratios (>95%) did not show a significant difference from forelimb data. Hindlimb PVF in ponies was found to be slightly higher when compared to data reported for horses even though the ponies moved at a similar or lower relative velocity. The contact area had low intra-individual variability and was significantly smaller in the hind- than in the fore-hooves. A larger contact area was significantly associated with lower peak vertical pressure (PVP) but higher PVF and VI. No significant differences between left and right sides were found for contact area or loading variables. Pressure plate measurements demonstrated a significant association between hoof contact area and limb loading, in addition to intrinsic differences between fore and hindlimb locomotor function. The pressure plate provides the clinician with a tool to quantify simultaneously contralateral differences in hoof contact area and limb loading. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Unloading performances and stabilizing practices for columnar jointed basalt: A case study of Baihetan hydropower station

    Directory of Open Access Journals (Sweden)

    Qixiang Fan


    Full Text Available The columnar jointed rock mass (CJR, composed of polygonal cross-sectional columns cut by several groups of joints in various directions, was exposed during the excavations of the Baihetan hydropower station, China. In order to investigate the unloading performances and the stability conditions during excavation of the columns, an experimental field study was performed. Firstly, on-site investigations indicated that the geotechnical problems, including rock relaxation, cracking and collapse, were the most prominent for the CJR Class I that contains intensive joint network and the smallest column sizes. Comprehensive field tests, including deformation measurement by multi-point extensometers, ultrasonic wave testing, borehole television observation and stress monitoring of rock anchors, revealed that the time-dependent relaxation of the CJRs was marked. The practical excavation experiences for the Baihetan columnar jointed rock masses, such as blasting scheme, supporting time of shotcrete and rock bolts, were presented in the excavations of the diversion tunnels. These detailed investigations and practical construction experiences can provide helpful information for similar geotechnical works in jointed rock mass.

  14. Filamentary MgB2 wires manufactured by different processes subjected to tensile loading and unloading (United States)

    Kováč, P.; Kulich, M.; Kopera, L.; Melišek, T.; Kováč, J.; Hušek, I.


    A reversible strain effect on the transport critical current (I c) of filamentary MgB2 wires manufactured by three different processes has been examined at 4.2 K and under an external field of 5 T. MgB2 wires with a Nb barrier and a Monel® outer sheath made by powder-in-tube ex situ, in situ and by diffusion of magnesium into the boron process, have been examined. The wire samples were loaded and partially unloaded at progressively higher strain levels to determine the irreversible strain limit (ε irr), which is defined as the ultimate strain where the critical current (I c) is still reversible. It was found that the strain tolerances of the tested MgB2 wires are affected by the production process. The highest annealing temperature (>900 °C), applied in the ex situ process, causes an apparent softening of the Monel® and, together with the poor grain connectivity of MgB2 filaments, leads to the lowest strain tolerance (ε irr = 0.20%). The best grain connectivity, in internal Mg diffusion (IMD)-made MgB2, combined with a stronger Monel® sheath (heat treated at a lower temperature ∼640 °C) results in the best strain tolerance (ε irr = 0.55%).

  15. Effect of unloading followed by reloading on expression of collagen and related growth factors in rat tendon and muscle

    DEFF Research Database (Denmark)

    Heinemeier, K M; Olesen, J L; Haddad, F


    were subjected to hindlimb suspension (HS) for 7 or 14 days, followed by 2, 4, 8, or 16 days of reload (RL) (n = 8 in each group). Age-matched controls were included for day 0, day 14 HS, and day 16 RL (n = 8). mRNA expression levels for collagen I (COL1A1), collagen III (COL3A1), TGF-beta1, connective...... mRNA levels were unaltered by HS, although collagen III tended to decrease in muscle at day 7 HS. IGF-I isoforms were significantly induced in tendon after 7 days of HS (P day 14 HS (P

  16. Role of adrenergic receptors in the caffeine-induced increase in ...

    African Journals Online (AJOL)

    The present study was designed to investigate the effects of alpha and beta adrenergic receptor blockers on caffeine-induced increase in canine hindlimb glucose uptake. The study was carried out on fasted male anaesthetized dogs divided into five groups (5dogs per group). Each dog was given a bolus injection of normal ...

  17. Gas turbine control : Modifications for: availability and limitation of spinning reserve and limitation of non-desired unloading


    Agüero, Jorge Luis; Beroqui, Mario César; Di Pasquo, H.


    This paper presents several modifications developed in a gas turbine control system. One of the modifications made in turbine control limits speed deviations to the governor. Consequently, this modification limits turbine power delivered -positive and negative- for Primary Control of Frequency purposes. In addition, this modification avoids that large, sudden power unloading takes place when the grid frequency recovers from a big dip, while original operational control modes are active. To...

  18. [Applied anatomy of the distal "vinculum tendinis" in the fetlock tendon sheath of the hindlimb in cattle]. (United States)

    Waibl, H; Herrmann, J; Rehage, J; Lorenzi, P; Constantinescu, G


    A relatively thick (diameter approximately 2 mm), ropelike (length ca. 20 mm) and elastic "Vinculum tendinis" connects--within the fetlock tendon sheath--the dorsal side of the deep digital flexor tendon with the dorsal part of the Manica flexoria (the communicating band of the Musculus interosseous medius to the superficial digital flexor tendon). The extensive fetlock tendon sheath can be involved in diseases such as aseptic and septic inflammations. Spreading of these inflammations makes in some of these cases the partial resection of the tendon of the deep digital flexor muscle and the cutting of these Vincula necessary. The results of this contribution, collected from 60 hindlimbs of adult bovines show variations in number, length, diameter and extent and the inner structure with blood vessels and nerves.

  19. Computational analysis of the effect of the control model of intraaorta pump on ventricular unloading and vessel response. (United States)

    Gu, Kaiyun; Chang, Yu; Gao, Bin; Liu, Youjun


    The intraaorta pump is a novel left ventricular assist device (LVAD) whose hemodynamic effects on the circulatory system is unknown. This article aims to evaluate the different effects on the circulatory system supported by the intraaorta pump. In this article, the pump is controlled by three control strategies, including the continuous flow method, the constant rotational speed, and the constant pressure head. A cardiovascular pump system, which includes cardiovascular circulation, intraaorta pump, and regulating mechanisms of systemic circulation, has been proposed. Left ventricle pressure (LVP), end-diastolic volume (EDV), and left ventricular external work (LVEW) were used to evaluate the degree of ventricular unloading. The pulsatile index (PI), which is defined as a ratio of pulse pressure and mean arterial pressure (MAP), was used to evaluate the effect of the vessel response by three control strategies. The comparison results showed that LVP and EDV were lower than those measured before the intraaorta pump was implanted. For LVEW, the constant pressure head strategy provided a superior ventricular unloading compared with other strategies. Support of the pump led to the lower pulsatility by the three models. However, the PI of the constant pressure head was the most at 0.37. In conclusion, these results indicate that the intraaorta pump controlled by constant pressure head strategy provides superior ventricular unloading and pulsatility of the vessel.


    Directory of Open Access Journals (Sweden)

    Mei-Chich Hsu


    Full Text Available In the present study we investigated the interactive effects of insulin and carbohydrate on glycogen replenishment in different rat hindlimb muscles. Forty male Sprague Dawley rats were assigned to 5 groups, including 1 sedentary control with carbohydrate supplement (2 g glucose · kg body wt-1, 2 sedentary rats with 16 hours recovery, carbohydrate and insulin (0.5 U · kg body wt-1, 3 swimming without recovery, 4 swimming with 16 hours recovery and carbohydrate supplement, and 5 swimming with 16 hours recovery, carbohydrate and insulin. The swimming protocol consisted of two 3 h swimming sections, which were separated by a 45 min rest. The insulin and carbohydrate were administered to the rats immediately after exercise. At the end of the experiment, the soleus (S, plantaris (P, quadriceps (Q and gastrocnemius (G were surgically excised to evaluate glycogen utilization and replenishment. We observed that glycogen utilization was significantly lower in G and Q than S and P during swimming (p <0.05, and S showed the greatest capacity of glycogen resynthesis after post-exercise recovery (p <0.05. In the sedentary state, the glycogen synthesis did not differ among hindlimb muscles during insulin and carbohydrate treatments. Interestingly, with insulin and carbohydrate, the glycogen resynthesis in S and P were significantly greater than in Q and G following post-exercise recovery (p <0.05. We therefore concluded that the soleus and plantaris are the primary working muscles during swimming, and the greatest glycogen replenishment capacity of the soleus during post-exercise recovery is likely due to its highest insulin sensitivity.

  1. Role of simvastatin and/or antioxidant vitamins in therapeutic angiogenesis in experimental diabetic hindlimb ischemia: effects on capillary density, angiogenesis markers, and oxidative stress. (United States)

    El-Azab, Mona F; Hazem, Reem M; Moustafa, Yasser M


    Therapeutic angiogenesis has emerged as an attractive approach for the management of peripheral arterial disease in diabetic patients. Oxidative stress generated and aggravated by prolonged hyperglycemia may interfere with and destroy the newly formed blood vessels. Angiogenic effect of simvastatin has been reported; however, its exact mechanism is yet to be evaluated. In addition, the exact role of antioxidant vitamins in diabetic peripheral arterial disease is still controversial. The present study was undertaken to investigate the therapeutic potential of simvastatin and antioxidant vitamins (E and C) and their combined effects on angiogenesis in diabetic hind-limb ischemia. Streptozotocin diabetic rats were treated for 6 weeks with simvastatin either alone or in combination with vitamin E or vitamin C. Parameters of angiogenesis, nitric oxide, heme oxygenase-1 (HO-1), and oxidative stress markers were evaluated. CD31 immunostaining revealed an increased capillary density in ischemic gastrocnemious tissue of diabetic rats treated with either simvastatin or its combination with vitamin C. This effect was accompanied by up-regulated plasma levels of HO-1, nitric oxide, vascular endothelial growth factor (VEGF) and its intra-muscular receptor type-2 (Flk-1). Tissue reduced glutathione and antioxidant enzymes activities were normalized in groups treated with antioxidant vitamins or their combination with simvastatin with concomitant blunting of lipid peroxidation. Vitamins E and C, through their antioxidant effects, evidently enhanced the angiogenic effect of simvastatin in ischemic diabetic muscle. Hence, the use of antioxidant vitamins combined with statins to induce therapeutic angiogenesis is a promising strategy in the management of diabetes-associated peripheral arterial disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. The nonlinear unloading behavior of a typical Ni-based superalloy during hot deformation: a new elasto-viscoplastic constitutive model (United States)

    Chen, Ming-Song; Lin, Y. C.; Li, Kuo-Kuo; Chen, Jian


    The nonlinear unloading behavior of a typical Ni-based superalloy is investigated by hot compressive experiments with intermediate unloading-reloading cycles. The experimental results show that there are at least four types of unloading curves. However, it is found that there is no essential difference among four types of unloading curves. The variation curves of instantaneous Young's modulus with stress for all types of unloading curves include four segments, i.e., three linear elastic segments (segments I, II, and III) and one subsequent nonlinear elastic segment (segment IV). The instantaneous Young's modulus of segments I and III is approximately equal to that of reloading process, while smaller than that of segment II. In the nonlinear elastic segment, the instantaneous Young's modulus linearly decreases with the decrease in stress. In addition, the relationship between stress and strain rate can be accurately expressed by the hyperbolic sine function. This study includes two parts. In the present part, the characters of unloading curves are discussed in detail, and a new elasto-viscoplastic constitutive model is proposed to describe the nonlinear unloading behavior based on the experimental findings. While in the latter part (Chen et al. in Appl Phys A. doi: 10.1007/s00339-016-0385-0, 2016), the effects of deformation temperature, strain rate, and pre-strain on the parameters of this new constitutive model are analyzed, and a unified elasto-viscoplastic constitutive model is proposed to predict the unloading behavior at arbitrary deformation temperature, strain rate, and pre-strain.

  3. Left ventricular volume unloading with axial and centrifugal rotary blood pumps. (United States)

    Giridharan, Guruprasad A; Koenig, Steven C; Soucy, Kevin G; Choi, Young; Pirbodaghi, Tohid; Bartoli, Carlo R; Monreal, Gretel; Sobieski, Michael A; Schumer, Erin; Cheng, Allen; Slaughter, Mark S


    Axial (AX) and centrifugal (CFG) rotary blood pumps have gained clinical acceptance for the treatment of advanced heart failure. Differences between AX and CFG designs and mechanism of blood flow delivery may offer clinical advantages. In this study, pump characteristics, and acute physiologic responses during support with AX (HeartMate II) and CFG (HVAD) left ventricular assist devices (LVAD) were investigated in mock loop and chronic ischemic heart failure bovine models. In the mock loop model, pump performance was characterized over a range of pump speeds (HeartMate II: 7,000-11,000 rpm, HVAD: 2,000-3,600 rpm) and fluid viscosities (2.7 cP, 3.2 cP, 3.7 cP). In the ischemic heart failure bovine model, hemodynamics, echocardiography, and end-organ perfusion were investigated. CFG LVAD had a flatter HQ curve, required less power, and had a more linear flow estimation relation than AX LVAD. The flow estimation error for the AX LVAD (±0.9 L/min at 2.7 cP, ±0.7 L/min at 3.2 cP, ±0.8 L/min at 3.7 cP) was higher than the CFG LVAD (±0.5 L/min at 2.7 cP, ±0.2 L/min at 3.2 cP, ±0.5 L/min at 3.7 cP). No differences in acute hemodynamics, echocardiography, or end-organ perfusion between AX and CFG LVAD over a wide range of support were statistically discernible. These findings suggest no pronounced acute differences in LV volume unloading between AX and CFG LVAD.

  4. Influence of Aggregate Gradation on the Longitudinal Wave Velocity Changes in Unloaded Concrete (United States)

    Teodorczyk, Michał


    Diagnosis is an important factor in the assessment of structural and operational condition of a concrete structure. Among diagnostic methods, non-destructive testing methods play a special role. Acoustic emission evaluation based on the identification and location of destructive processes is one of such methods. The 3D location of AE events and moment tensor of fracture analysis are calculated by longitudinal wave velocity. Therefore, determining the velocity of longitudinal wave of concrete and the impact of the material and destructive factors are of essential importance. This paper reports the investigation of the effect of aggregate gradation on the change in wave velocity of unloaded concrete. The investigation was carried out on six 150 x 150 x 600 mm elements. Three elements contained aggregate fraction 8/16 mm and the other three were made with aggregate fraction 2/16 mm. Two acoustic emission sensors were used on the surface of the elements, and the wave was generated by the Hsu – Nielsen source. Longitudinal wave velocities for each group of elements were calculated and statistical test of significance was used for the comparison of two means. The results of the test indicated a substantial effect of the aggregate grain size on the change in longitudinal wave velocity. The average wave velocity in the concrete containing 8/16 mm fraction was 4672 m/s. In the concrete with 2/16 mm fraction, the velocity decreased to 4373 m/s. The velocity of the wave decreases at larger quantities of aggregate. The propagating longitudinal wave encounters more aggregate grains on its way and is reflected, also from air voids, multiple times and so its velocity is noticeably lower in the concrete with the 2/16 fraction. Thus, to be able to accurately locate AE events and analyse moment tensor during concrete structure testing, the aggregate grain size used in the concrete should be taken into account.

  5. Hind limb unloading of mice modulates gene expression at the protein and mRNA level in mesenchymal bone cells

    Directory of Open Access Journals (Sweden)

    Palmieri Daniela


    Full Text Available Abstract Background We investigated the extent, modalities and reversibility of changes at cellular level in the expression of genes and proteins occurring upon Hind limb unloading (HU in the tibiae of young C57BL/6J male mice. We focused on the effects of HU in chondrogenic, osteogenic, and marrow mesenchymal cells. Methods We analyzed for expression of genes and proteins at two time points after HU (7 and 14 days, and at 14 days after recovery from HU. Levels of mRNAs were tested by in situ hybridization. Protein levels were tested by immunohistochemistry. We studied genes involved in osteogenesis (alkaline phosphatase (AP, osteocalcin (OC, bonesialoprotein (BSP, membrane type1 matrix metalloproteinase (MT1-MMP, in extracellular matrix (ECM formation (procollagenases (BMP1, procollagenase enhancer proteins (PCOLCE and remodeling (metalloproteinase-9 (MMP9, RECK, and in bone homeostasis (Stro-1, CXCL12, CXCR4, CD146. Results We report the following patterns and timing of changes in gene expression induced by HU: 1 transient or stable down modulations of differentiation-associated genes (AP, OC, genes of matrix formation, maturation and remodelling, (BMP1, PCOLCEs MMP9 in osteogenic, chondrogenic and bone marrow cells; 2 up modulation of MT1-MMP in these same cells, and uncoupling of its expression from that of AP; 3 transient down modulation of the osteoblast specific expression of BSP; 4 for genes involved in bone homeostasis, up modulation in bone marrow cells at distal epiphysis for CXCR4, down modulation of CXCL12, and transient increases in osteoblasts and marrow cells for Stro1. 14 days after limb reloading expression returned to control levels for most genes and proteins in most cell types, except AP in all cells, and CXCL12, only in bone marrow. Conclusions HU induces the coordinated modulation of gene expression in different mesenchymal cell types and microenvironments of tibia. HU also induces specific patterns of expression for

  6. In vivo open-bore MRI reveals region- and sub-arc-specific lengthening of the unloaded human posterior cruciate ligament.

    Directory of Open Access Journals (Sweden)

    Alison J King

    Full Text Available Open-bore MRI scanners allow joint soft tissue to be imaged over a large, uninterrupted range of flexion. Using an open-bore scanner, 3D para-sagittal images of the posterior cruciate ligament (PCL were collected from seven healthy subjects in unloaded, recumbent knee extension and flexion. PCL length was measured from one 2D MRI slice partition per flexion angle, per subject. The anterior surface of the PCL lengthened significantly between extension and flexion (p<0.001. Conversely, the posterior surface did not. Changes were not due to the PCL moving relative to the 2D slice partition; measurements made from 3D reconstructions, which compensated for PCL movement, did not differ significantly from measurements made from 2D slice partitions. In a second experiment, videos of knee flexion were made by imaging two subjects at several flexion angles. Videos allowed soft tissue tracking; examples are included. In a third experiment, unloaded knees of seven healthy, recumbent subjects were imaged at extension and at 40°, 70°, 90°, 100°, 110° and 120° flexion. The distance between PCL attachments increased between extension and 100°, and then decreased (p<0.001. The anterior surface of the PCL lengthened over the flexion angles measured (p<0.01. The posterior surface of the PCL lengthened between extension and 40° and then shortened (p<0.001. Both attachment separation and anterior surface length increased dramatically between extension and 40°, but varied less afterwards. Results indicate that PCL dynamics differ between terminal extension and active function sub-arcs. Also, attachment separation cannot predict the lengthening of all parts of the PCL, nor can lengthening of one part of the PCL predict the lengthening of another part. A potential connection between lengthening and loading is discussed. We conclude that low-field MRI can assess ligament lengthening during flexion, and that the dynamics of the PCL for any given region and sub

  7. All-trans-retinoic acid inhibits chondrogenesis of rat embryo hindlimb bud mesenchymal cells by downregulating p53 expression (United States)



    Despite the well-established role of all-trans-retinoic acid (ATRA) in congenital clubfoot (CCF)-like deformities in in vivo models, the essential cellular and molecular targets and the signaling mechanisms for ATRA-induced CCF-like deformities remain to be elucidated. Recent studies have demonstrated that p53 and p21, expressed in the hindlimb bud mesenchyme, regulate cellular proliferation and differentiation, contributing to a significant proportion of embryonic CCF-like abnormalities. The objective of the present study was to investigate the mechanisms for ATRA-induced CCF, by assessing ATRA-regulated chondrogenesis in rat embryo hindlimb bud mesenchymal cells (rEHBMCs) in vitro. The experimental study was based on varying concentrations of ATRA exposure on embryonic day 12.5 rEHBMCs in vitro. The present study demonstrated that ATRA inhibited the proliferation of cells by stimulating apoptotic cell death of rEHBMCs. It was also observed that ATRA induced a dose-dependent reduction of cartilage nodules compared with the control group. Reverse transcription-polymerase chain reaction and western blotting assays revealed that the mRNA and protein expression of cartilage-specific molecules, including aggrecan, Sox9 and collagen, type II, α 1 (Col2a1), were downregulated by ATRA in a dose-dependent manner; the mRNA levels of p53 and p21 were dose-dependently upregulated from 16 to 20 h of incubation with ATRA, but dose-dependently downregulated from 24 to 48 h. Of note, p53 and p21 were regulated at the translational level in parallel with the transcription with rEHBMCs treated with ATRA. Furthermore, the immunofluorescent microscopy assays indicated that proteins of p53 and p21 were predominantly expressed in the cartilage nodules. The present study demonstrated that ATRA decreases the chondrogenesis of rEHBMCs by inhibiting cartilage-specific molecules, including aggrecan, Sox9 and Col2al, via regulating the expression of p53 and p21. PMID:25738595

  8. Expression profile of plakin cross-linking proteins in short-term denervated mouse hindlimb skeletal muscle

    Directory of Open Access Journals (Sweden)

    Blouin P


    Full Text Available Patrick Blouin,1 Olivier Serresse,1 Sandra C Dorman,1,2 Céline Larivière,1–3 1School of Human Kinetics, 2Northern Ontario School of Medicine, 3Biomolecular Sciences, Laurentian University, Sudbury, ON, Canada Purpose: Skeletal muscle atrophy linked to neuromuscular inactivity is a complex phenomenon involving widespread alteration of muscle structure and function. Plakin cross-linking proteins are important structural elements that are expressed in skeletal muscles, which require resistance to mechanical stress. The plakin proteins most prevalent in skeletal muscles are plectin, dystonin, and microtubule-actin cross-linking factor (MACF. The expression profile of plakin cross-linking proteins in skeletal muscles during atrophy is poorly understood. We therefore investigated the expression profile of plectin, dystonin, and MACF in mouse hindlimb muscles undergoing denervation-induced atrophy.Materials and methods: Quantitative polymerase chain reaction and Western blotting were performed to assess plakin mRNA and protein expression in mouse gastrocnemius muscles that were denervated for 1 day, 3 days, 7 days, and 14 days. The left hindlimb muscles were denervated by severing the left sciatic nerve, and the contralateral limb muscles served as sham control muscles. The mRNA expression of myogenin and acetylcholinesterase was measured in parallel and served as controls.Results: As expected, myogenin mRNA expression was substantially induced in denervated muscles (13-fold induction, whereas acetylcholinesterase expression was significantly and progressively suppressed (90% reduction in denervated skeletal muscles. In comparison, we found that plectin and dystonin mRNA expression were progressively reduced by ~50% at day 14 denervation time point, but the protein levels remained relatively constant. On the other hand, MACF expression was upregulated approximately threefold by day 7 denervation at both the mRNA and protein levels

  9. Transport management, loading and unloading of dangerous goods : programs for it management; Gestion del transporte, la carga y la descarga de las mercancias peligrosas: programas de ayuda a la gestion

    Energy Technology Data Exchange (ETDEWEB)

    Manas Lahoz, J. L.


    This article gives an account of the different stages to the management of the transport and/or loading and/or unloading and the computer programs for carrying out the management of Dangerous Goods (DG), which are related to specific aspects regarding loading, unloading and transport of such objects and substances as are classified under the Regulations for the Transport, Loading and Unloading of Dangerous goods. In particular, the ADR and the national Regulations for the Transport of DG Road. (Author)

  10. On the Load-Unload (L-U) and Force-Release (F-R) Algorithms for Simulating Brittle Fracture Processes via Lattice Models

    KAUST Repository

    Liu, Jinxing


    General summaries on the load-unload and force-release methods indicate that the two methods are efficient for different-charactered quasi-static failures; therefore, it is important to choose the right one for different applications. Then we take, as an example, the case where the release of the ruptured element\\'s internal force is infinitely slower than the relaxation of the lattice system and analyze why the force-release method works better than the load-unload method in this particular case. Different trial deformation fields are used by them to track the next equilibrium state. Force-release method ensures that the deformation throughout the whole failure process coincides exactly with the controlled-displacement boundary conditions and we utilize the \\'left modulus\\' concept to prove that this method satisfies the energetic evolution in the force-displacement diagram; both of which are not satisfied by the load-unload method. To illustrate that the force-release method is not just another form of the load-unload method, a tensile test on a specifically designed system is analyzed to further compare the above two methods, showing that their predicted sequences of elemental failures can be different. In closing, we simulate the uniaxial tensile test on a beam lattice system by the load-unload and force-release methods and exploit the details of the resulting fracture processes. © The Author(s), 2011.

  11. Anatomic and functional leg-length inequality: A review and recommendation for clinical decision-making. Part II, the functional or unloaded leg-length asymmetry

    Directory of Open Access Journals (Sweden)

    Knutson Gary A


    Full Text Available Abstract Background Part II of this review examines the functional "short leg" or unloaded leg length alignment asymmetry, including the relationship between an anatomic and functional leg-length inequality. Based on the reviewed evidence, an outline for clinical decision making regarding functional and anatomic leg-length inequality will be provided. Methods Online databases: Medline, CINAHL and Mantis. Plus library searches for the time frame of 1970–2005 were done using the term "leg-length inequality". Results and Discussion The evidence suggests that an unloaded leg-length asymmetry is a different phenomenon than an anatomic leg-length inequality, and may be due to suprapelvic muscle hypertonicity. Anatomic leg-length inequality and unloaded functional or leg-length alignment asymmetry may interact in a loaded (standing posture, but not in an unloaded (prone/supine posture. Conclusion The unloaded, functional leg-length alignment asymmetry is a likely phenomenon, although more research regarding reliability of the measurement procedure and validity relative to spinal dysfunction is needed. Functional leg-length alignment asymmetry should be eliminated before any necessary treatment of anatomic LLI.

  12. Seven skeletal muscles rich in slow muscle fibers may function to sustain neutral position in the rodent hindlimb. (United States)

    Hitomi, Yoshiaki; Kizaki, Takako; Watanabe, Sumiko; Matsumura, George; Fujioka, Yasunori; Haga, Shukoh; Izawa, Tetsuya; Taniguchi, Naoyuki; Ohno, Hideki


    Skeletal muscles consist of slow-twitch and fast-twitch muscle fibers, which have distinct physiological and biochemical properties. The muscle fiber composition determines the contractile velocity and fatigability of a particular skeletal muscle. We analyzed the systemic distribution of slow muscle fibers in all rodent skeletal muscles by myosin ATPase staining and found that only seven hindlimb skeletal muscles were extremely rich in slow muscle fibers. These included the mouse piriformis (56.5%), gluteus minimus (35.7%), vastus intermedius (24.7%), quadratus femoris (69.9%), adductor brevis (44.3%), gracilis (24.6%), and soleus muscles (35.1%). In mice, the relative proportion of slow muscle fibers did not exceed 15% in skeletal muscles in other regions. The distribution of slow muscle fibers was well conserved in rats and rabbits. The soleus muscle is an important antigravity muscle in both rodents and humans; therefore, these skeletal muscles rich in slow muscle fibers might play an important role in sustaining neutral alignment of the lower extremity.

  13. Intra-specific variability of hindlimb length in the palmate newt: an indicator of population isolation induced by habitat fragmentation? (United States)

    Trochet, Audrey; Le Chevalier, Hugo; Baillat, Boris; Barthe, Laurent; Pottier, Gilles; Calvez, Olivier; Ribéron, Alexandre; Blanchet, Simon


    Habitat fragmentation is one of the main drivers of global amphibian decline. Anthropogenic landscape elements can act as barriers, hindering the dispersal that is essential for maintaining gene flow between populations. Dispersal ability can be influenced by locomotor performance, which in turn can depend on morphological traits, such as hindlimb length (HLL) in amphibians. Here, we tested relationships between HLL and environmental variables--road types, forests and agricultural lands--among 35 sub-populations of palmate newts (Lissotriton helveticus) in southwestern France. We expected roads to select for short-legged newts due to a higher mortality of more mobile individuals (long-legged newts) when crossing roads. Accordingly, short-legged newts were found in the vicinity of roads, whereas long-legged newts were found closer to forests and in ponds close geographically to another water body. HLL in newts was hence influenced by habitat types in a heterogeneous landscape, and could therefore be used as an indicator of population isolation in a meta-population system. © 2016 The Author(s).

  14. The adaptational strategies of the hindlimb muscles in the Tenrecidae species including the aquatic web-footed tenrec (Limnogale mergulus). (United States)

    Endo, Hideki; Yonezawa, Takahiro; Rakotondraparany, Felix; Sasaki, Motoki; Hasegawa, Masami


    The hindlimb muscles in four species of Tenrecidae (Oryzoryctinae: Talazac long-tailed tenrec and web-footed tenrec, Tenrecinae: lesser hedgehog tenrec, and streaked tenrec), were examined macroscopically. The weight ratios of the muscles to the body in the oryzoryctinid species are larger than those in Tenrecinae, since the Oryzoryctinae species have an obviously smaller body from the evolutionary point of view. It can be primarily pointed out that the adaptation of the body size is different between the two subfamilies, and secondarily, that functional adaptation to locomotion is complete within each subfamily. The weight data and the morphological findings demonstrate that the web-footed tenrec possesses an extraordinary large M. semimembranosus in comparison to the Talazac long-tailed tenrec in their weight ratios. This muscle may act as a strong flexor motor in the knee joint during the aquatic locomotion of the web-footed tenrec. Since the other muscles of the web-footed tenrec are similar to those of the Talazac long-tailed tenrec regards weight ratio data, we think that the web-footed tenrec may have derived from a terrestrial ancestor such as the long-tailed tenrecs. In Tenrecinae the streaked tenrec is equipped with larger Mm. adductores, M. semimembranosus and M. triceps surae than the lesser hedgehog tenrec. This species is adapted to fossorial life derived from non-specialized ancestors within the evolutionary lines of the spiny tenrecs.

  15. Repeatability, Reproducibility and Standardisation of a Laser Doppler Imaging Technique for the Evaluation of Normal Mouse Hindlimb Perfusion

    Directory of Open Access Journals (Sweden)

    Arturo Brunetti


    Full Text Available Background. Preclinical perfusion studies are useful for the improvement of diagnosis and therapy in dermatologic, cardiovascular and rheumatic human diseases. The Laser Doppler Perfusion Imaging (LDPI technique has been used to evaluate superficial alterations of the skin microcirculation in surgically induced murine hindlimb ischemia. We assessed the reproducibility and the accuracy of LDPI acquisitions and identified several critical factors that could affect LDPI measurements in mice. Methods. Twenty mice were analysed. Statistical standardisation and a repeatability and reproducibility analysis were performed on mouse perfusion signals with respect to differences in body temperature, the presence or absence of hair, the type of anaesthesia used for LDPI measurements and the position of the mouse body. Results. We found excellent correlations among measurements made by the same operator (i.e., repeatability under the same experimental conditions and by two different operators (i.e., reproducibility. A Bland-Altman analysis showed the absence of bias in repeatability (p = 0.29 or reproducibility (p = 0.89. The limits of agreement for repeatability were –0.357 and –0.033, and for reproducibility, they were –0.270 and 0.238. Significant differences in perfusion values were observed in different experimental groups. Conclusions. Different experimental conditions must be considered as a starting point for the evaluation of new drugs and strategic therapies.

  16. Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation. (United States)

    Holfeld, Johannes; Tepeköylü, Can; Blunder, Stefan; Lobenwein, Daniela; Kirchmair, Elke; Dietl, Marion; Kozaryn, Radoslaw; Lener, Daniela; Theurl, Markus; Paulus, Patrick; Kirchmair, Rudolf; Grimm, Michael


    Low energy shock waves have been shown to induce angiogenesis, improve left ventricular ejection fraction and decrease angina symptoms in patients suffering from chronic ischemic heart disease. Whether there is as well an effect in acute ischemia was not yet investigated. Hind-limb ischemia was induced in 10-12 weeks old male C57/Bl6 wild-type mice by excision of the left femoral artery. Animals were randomly divided in a treatment group (SWT, 300 shock waves at 0.1 mJ/mm2, 5 Hz) and untreated controls (CTR), n = 10 per group. The treatment group received shock wave therapy immediately after surgery. Higher gene expression and protein levels of angiogenic factors VEGF-A and PlGF, as well as their receptors Flt-1 and KDR have been found. This resulted in significantly more vessels per high-power field in SWT compared to controls. Improvement of blood perfusion in treatment animals was confirmed by laser Doppler perfusion imaging. Receptor tyrosine kinase profiler revealed significant phosphorylation of VEGF receptor 2 as an underlying mechanism of action. The effect of VEGF signaling was abolished upon incubation with a VEGFR2 inhibitor indicating that the effect is indeed VEGFR 2 dependent. Low energy shock wave treatment induces angiogenesis in acute ischemia via VEGF receptor 2 stimulation and shows the same promising effects as known from chronic myocardial ischemia. It may therefore develop as an adjunct to the treatment armentarium of acute muscle ischemia in limbs and myocardium.

  17. The effects of a varus unloader brace for lateral tibiofemoral osteoarthritis and valgus malalignment after anterior cruciate ligament reconstruction: a single case study. (United States)

    Hart, H F; Ackland, D C; Schache, A G; Pandy, M G; Collins, N J; Crossley, K M


    We investigated the immediate effects of a varus knee brace on knee symptoms and knee-joint biomechanics in an individual with predominant lateral tibiofemoral joint osteoarthritis (TFJOA) and valgus malalignment after anterior cruciate ligament (ACL) reconstruction. A varus unloader brace was prescribed to a 48-year-old male with predominant lateral radiographic and symptomatic TFJOA and valgus malalignment eight-years following ACL reconstruction. During a step-down task, the participant rated knee pain, task-difficulty, knee-stability and knee-confidence on four separate visual analogue scales. Quantitative gait analysis was conducted during self-selected walking trials under three test conditions in a randomized order: (i) no brace; (ii) brace without frontal plane adjustment (no varus re-alignment); and (ii) brace with frontal plane adjustment (varus re-alignment). Post-processing of gait data involved calculation of knee kinematics and net joint moments for the reconstructed limb. The participant reported improved pain (3%), task difficulty (41%), stability (46%) and confidence (49%) when performing the step-down task with the brace. The varus brace resulted in immediate reductions in knee abduction angle (24%) and internal rotation angle (56%), and increased knee adduction moment (18%). These findings provide preliminary evidence for potentially beneficial effects of bracing on knee-symptoms and biomechanics in individuals with lateral TFJOA after reconstruction.

  18. Effect of Recycling and Autoclave Sterilization on the Unloading Forces of NiTi Closed-Coil Springs: An In Vitro Study. (United States)

    Momeni Danaei, Sh; Oshagh, M; Khozaei, A


    Clinicians use the NiTi coil springs frequently for its appropriate mechanical properties. The aim of this study was to determine the effect of recycling and autoclave sterilization on the unloading forces of NiTi closed coil springs. Fourteen NiTi closed coil spring with the length of 9mm were selected. Each coil was stretched to a peak extension of 12 mm. A universal testing machine was used to acquire load/deflection curve of the coil springs at 25±2°C. The influence of thermocycling (1000 cycles,5-55°C), autoclaving (134°C, 32PSI, 3min) and mechanical strain (9mm extension) which simulated the oral condition, were considered. Data were statistically analyzed by adopting Repeated Measures MANOVA Paired t-Test. Autoclaving in the 1, 4, 6 steps increased the force levels of coil springs about 2-5gf (p< 0.01). Thermocycling reduced their force levels about 4-6gf. Prolonged strain at 3, 5 steps decreased the magnitude of forces levels about 3-4gf. Concerning all the limitations; according to the results of this study; it is possible to recycle Ni-Ti closed-coil springs without significant reduction in their force levels.

  19. An electromyographic and kinematic comparison between an extendable conveyor system and an articulating belt conveyor used for truck loading and unloading tasks. (United States)

    Lavender, Steven A; Nagavarapu, Shasank; Allread, W Gary


    Many retail distribution centers (DCs) manually load and unload boxes into or out of trailers and shipping containers. This study investigated whether an articulating belt conveyor with a height adjustable platform, positioned at the end of an extendable conveyor, significantly reduces shoulder and back muscle loading and the spine kinematics associated with these tasks. Electromyographic and kinematic data were collected from eight volunteer employees as trailers at a shoe DC were unloaded and from nine volunteer employees as trailers at an apparel DC were loaded. Participants in this repeated measures study handled boxes with a conventional powered extendable conveyor system and with the articulating belt conveyor positioned at the end of the extendable conveyor. Bilaterally the normalized activation levels of the erector spinae and anterior deltoid muscles were reduced when loading and unloading boxes with the articulating belt conveyor. Spine movement speeds were also reduced with the articulating conveyor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling (United States)

    Theriot, Corey A.; Zanello, Susana B.


    Preliminary data from a prior tissue-sharing experiment has suggested that early growth response protein-1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia- or inflammation-driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated-weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS-induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell-specific isolectin binding, coupled to Alexa-488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z-axis. This new confocal microscope has the added capability of dye separation using the Linear

  1. Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

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    Marcos L. Ferreira-Neto


    Full Text Available Electrical stimulation of the hypothalamus produces cardiovascular adjustments consisting of hypertension, tachycardia, visceral vasoconstriction and hindlimb vasodilation. Previous studies have demonstrated that hindlimb vasodilation is due a reduction of sympathetic vasoconstrictor tone and to activation of beta2-adrenergic receptors by catecholamine release. However, the existence of a yet unidentified vasodilator mechanism has also been proposed. Recent studies have suggested that nitric oxide (NO may be involved. The aim of the present study was to investigate the role of NO in the hindquarter vasodilation in response to hypothalamic stimulation. In pentobarbital-anesthetized rats hypothalamic stimulation (100 Hz, 150µA, 6 s produced hypertension, tachycardia, hindquarter vasodilation and mesenteric vasoconstriction. Alpha-adrenoceptor blockade with phentolamine (1.5 mg/kg, iv plus bilateral adrenalectomy did not modify hypertension, tachycardia or mesenteric vasoconstriction induced by hypothalamic stimulation. Hindquarter vasodilation was strongly reduced but not abolished. The remaining vasodilation was completely abolished after iv injection of the NOS inhibitor L-NAME (20 mg/kg, iv. To properly evaluate the role of the mechanism of NO in hindquarter vasodilation, in a second group of animals L-NAME was administered before alpha-adrenoceptor blockade plus adrenalectomy. L-NAME treatment strongly reduced hindquarter vasodilation in magnitude and duration. These results suggest that NO is involved in the hindquarter vasodilation produced by hypothalamic stimulation.Em animais anestesiados a EE do hipotálamo produz um padrão de ajustes cardiovasculares caracterizado por hipertensão arterial, taquicardia, vasodilatação muscular e vasoconstrição mesentérica, entretanto, os mecanismos periféricos envolvidos nestes ajustes cardiovasculares ainda não foram completamente esclarecidos. O presente estudo teve como objetivo caracterizar

  2. Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation.

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    Johannes Holfeld

    Full Text Available OBJECTIVES: Low energy shock waves have been shown to induce angiogenesis, improve left ventricular ejection fraction and decrease angina symptoms in patients suffering from chronic ischemic heart disease. Whether there is as well an effect in acute ischemia was not yet investigated. METHODS: Hind-limb ischemia was induced in 10-12 weeks old male C57/Bl6 wild-type mice by excision of the left femoral artery. Animals were randomly divided in a treatment group (SWT, 300 shock waves at 0.1 mJ/mm2, 5 Hz and untreated controls (CTR, n = 10 per group. The treatment group received shock wave therapy immediately after surgery. RESULTS: Higher gene expression and protein levels of angiogenic factors VEGF-A and PlGF, as well as their receptors Flt-1 and KDR have been found. This resulted in significantly more vessels per high-power field in SWT compared to controls. Improvement of blood perfusion in treatment animals was confirmed by laser Doppler perfusion imaging. Receptor tyrosine kinase profiler revealed significant phosphorylation of VEGF receptor 2 as an underlying mechanism of action. The effect of VEGF signaling was abolished upon incubation with a VEGFR2 inhibitor indicating that the effect is indeed VEGFR 2 dependent. CONCLUSIONS: Low energy shock wave treatment induces angiogenesis in acute ischemia via VEGF receptor 2 stimulation and shows the same promising effects as known from chronic myocardial ischemia. It may therefore develop as an adjunct to the treatment armentarium of acute muscle ischemia in limbs and myocardium.

  3. Joint unloading implant modifies subchondral bone trabecular structure in medial knee osteoarthritis: 2-year outcomes of a pilot study using fractal signature analysis

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    Miller LE


    Full Text Available Larry E Miller,1,2 Miki Sode,3 Thomas Fuerst,3 Jon E Block2 1Miller Scientific Consulting, Inc., Asheville, NC, USA; 2The Jon Block Group, San Francisco, CA, USA; 3Bioclinica, Newark, CA, USA Background: Knee osteoarthritis (OA is largely attributable to chronic excessive and aberrant joint loading. The purpose of this pilot study was to quantify radiographic changes in subchondral bone after treatment with a minimally invasive joint unloading implant (KineSpring® Knee Implant System.Methods: Nine patients with unilateral medial knee OA resistant to nonsurgical therapy were treated with the KineSpring System and followed for 2 years. Main outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC pain, function, and stiffness subscores and independent core laboratory determinations of joint space width and fractal signature of the tibial cortex.Results: WOMAC scores, on average, improved by 92% for pain, 91% for function, and 79% for stiffness over the 2-year follow-up period. Joint space width in the medial compartment of the treated knee significantly increased from 0.9 mm at baseline to 3.1 mm at 2 years; joint space width in the medial compartment of the untreated knee was unchanged. Fractal signatures of the vertically oriented trabeculae in the medial compartment decreased by 2.8% in the treated knee and increased by 2.1% in the untreated knee over 2 years. No statistically significant fractal signature changes were observed in the horizontally oriented trabeculae in the medial compartment or in the horizontal or vertical trabeculae of the lateral compartment in the treated knee.Conclusion: Preliminary evidence suggests that the KineSpring System may modify knee OA disease progression by increasing joint space width and improving subchondral bone trabecular integrity, thereby reducing pain and improving joint function. Keywords: disease modification, KineSpring, joint space, pain, trabecular

  4. Dissociation between short-term unloading and resistance training effects on skeletal muscle Na+,K+-ATPase, muscle function, and fatigue in humans. (United States)

    Perry, Ben D; Wyckelsma, Victoria L; Murphy, Robyn M; Steward, Collene H; Anderson, Mitchell; Levinger, Itamar; Petersen, Aaron C; McKenna, Michael J


    Physical training increases skeletal muscle Na + ,K + -ATPase content (NKA) and improves exercise performance, but the effects of inactivity per se on NKA content and isoform abundance in human muscle are unknown. We investigated the effects of 23-day unilateral lower limb suspension (ULLS) and subsequent 4-wk resistance training (RT) on muscle function and NKA in 6 healthy adults, measuring quadriceps muscle peak torque; fatigue and venous [K + ] during intense one-legged cycling exercise; and skeletal muscle NKA content ([ 3 H]ouabain binding) and NKA isoform abundances (immunoblotting) in muscle homogenates (α 1-3 , β 1-2 ) and in single fibers (α 1-3 , β 1 ). In the unloaded leg after ULLS, quadriceps peak torque and cycling time to fatigue declined by 22 and 23%, respectively, which were restored with RT. Whole muscle NKA content and homogenate NKA α 1-3 and β 1-2 isoform abundances were unchanged with ULLS or RT. However, in single muscle fibers, NKA α 3 in type I (-66%, P = 0.006) and β 1 in type II fibers (-40%, P = 0.016) decreased after ULLS, with other NKA isoforms unchanged. After RT, NKA α 1 (79%, P = 0.004) and β 1 (35%, P = 0.01) increased in type II fibers, while α 2 (76%, P = 0.028) and α 3 (142%, P = 0.004) increased in type I fibers compared with post-ULLS. Despite considerably impaired muscle function and earlier fatigue onset, muscle NKA content and homogenate α 1 and α 2 abundances were unchanged, thus being resilient to inactivity induced by ULLS. Nonetheless, fiber type-specific downregulation with inactivity and upregulation with RT of several NKA isoforms indicate complex regulation of muscle NKA expression in humans. Copyright © 2016 the American Physiological Society.

  5. Disuse exaggerates the detrimental effects of alcohol on cortical bone (United States)

    Hefferan, Theresa E.; Kennedy, Angela M.; Evans, Glenda L.; Turner, Russell T.


    BACKGROUND: Alcohol abuse is associated with an increased risk for osteoporosis. However, comorbidity factors may play an important role in the pathogenesis of alcohol-related bone fractures. Suboptimal mechanical loading of the skeleton, an established risk factor for bone loss, may occur in some alcohol abusers due to reduced physical activity, muscle atrophy, or both. The effect of alcohol consumption and reduced physical activity on bone metabolism has not been well studied. The purpose of this study was to determine whether mechanical disuse alters bone metabolism in a rat model for chronic alcohol abuse. METHODS: Alcohol was administered in the diet (35% caloric intake) of 6-month-old male rats for 4 weeks. Rats were hindlimb-unloaded the final 2 weeks of the experiment to prevent dynamic weight bearing. Afterward, cortical bone histomorphometry was evaluated at the tibia-fibula synostosis. RESULTS: At the periosteal surface of the tibial diaphysis, alcohol and hindlimb unloading independently decreased the mineralizing perimeter, mineral apposition rate, and bone formation rate. In addition, alcohol, but not hindlimb unloading, increased endocortical bone resorption. The respective detrimental effects of alcohol and hindlimb unloading to inhibit bone formation were additive; there was no interaction between the two variables. CONCLUSIONS: Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.

  6. Transcranial magnetic stimulation (TMS) responses elicited in hindlimb muscles as an assessment of synaptic plasticity in spino-muscular circuitry after chronic spinal cord injury. (United States)

    Petrosyan, Hayk A; Alessi, Valentina; Sisto, Sue A; Kaufman, Mark; Arvanian, Victor L


    Electromagnetic stimulation applied at the cranial level, i.e. transcranial magnetic stimulation (TMS), is a technique for stimulation and neuromodulation used for diagnostic and therapeutic applications in clinical and research settings. Although recordings of TMS elicited motor-evoked potentials (MEP) are an essential diagnostic tool for spinal cord injured (SCI) patients, they are reliably recorded from arm, and not leg muscles. Mid-thoracic contusion is a common SCI that results in locomotor impairments predominantly in legs. In this study, we used a chronic T10 contusion SCI rat model and examined whether (i) TMS-responses in hindlimb muscles can be used for evaluation of conduction deficits in cortico-spinal circuitry and (ii) if plastic changes at spinal levels will affect these responses. In this study, plastic changes of transmission in damaged spinal cord were achieved by repetitive electro-magnetic stimulation applied over the spinal level (rSEMS). Spinal electro-magnetic stimulation was previously shown to activate spinal nerves and is gaining large acceptance as a non-invasive alternative to direct current and/or epidural electric stimulation. Results demonstrate that TMS fails to induce measurable MEPs in hindlimbs of chronically SCI animals. After facilitation of synaptic transmission in damaged spinal cord was achieved with rSEMS, however, MEPs were recorded from hindlimb muscles in response to single pulse TMS stimulation. These results provide additional evidence demonstrating beneficial effects of TMS as a diagnostic technique for descending motor pathways in uninjured CNS and after SCI. This study confirms the ability of TMS to assess plastic changes of transmission occurring at the spinal level. Published by Elsevier B.V.

  7. Inactivity-induced modulation of Hsp20 and Hsp25 content in rat hindlimb muscles. (United States)

    Huey, Kimberly A; Thresher, Jeffrey S; Brophy, Colleen M; Roy, Roland R


    Denervation decreases small heat shock protein (HSP) content in the rat soleus muscle; however, it is unknown whether this change is due to inactivity or absence of a nerve-muscle connection. Spinal cord isolation (SI) is a model of inactivity with an intact neuromuscular connection. After 7 days of SI, Hsp20 and Hsp25 levels in the soleus, plantaris, and adductor longus muscles were lower than in control rats, whereas Hsp20 was unchanged and Hsp25 increased in the tibialis anterior. The results for the soleus indicate that these small HSPs respond to inactivity and that this response is not influenced by neural activity-independent factors. Furthermore, the data indicate that these HSPs are impacted to a greater degree in muscles that are predominantly slow or have an antigravity function than in flexor muscles. Understanding the regulation of these HSPs during chronic reductions in neuromuscular activity may have valuable applications for conditions such as spinal cord injury.

  8. Manual unloading of the lumbar spine: can it identify immediate responders to mechanical traction in a low back pain population? A study of reliability and criterion referenced predictive validity. (United States)

    Swanson, Brian T; Riley, Sean P; Cote, Mark P; Leger, Robin R; Moss, Isaac L; Carlos, John


    To date, no research has examined the reliability or predictive validity of manual unloading tests of the lumbar spine to identify potential responders to lumbar mechanical traction. To determine: (1) the intra and inter-rater reliability of a manual unloading test of the lumbar spine and (2) the criterion referenced predictive validity for the manual unloading test. Ten volunteers with low back pain (LBP) underwent a manual unloading test to establish reliability. In a separate procedure, 30 consecutive patients with LBP (age 50·86±11·51) were assessed for pain in their most provocative standing position (visual analog scale (VAS) 49·53±25·52 mm). Patients were assessed with a manual unloading test in their most provocative position followed by a single application of intermittent mechanical traction. Post traction, pain in the provocative position was reassessed and utilized as the outcome criterion. The test of unloading demonstrated substantial intra and inter-rater reliability K = 1·00, P = 0·002, K = 0·737, P = 0·001, respectively. There were statistically significant within group differences for pain response following traction for patients with a positive manual unloading test (P0·05). There were significant between group differences for proportion of responders to traction based on manual unloading response (P = 0·031), and manual unloading response demonstrated a moderate to strong relationship with traction response Phi = 0·443, P = 0·015. The manual unloading test appears to be a reliable test and has a moderate to strong correlation with pain relief that exceeds minimal clinically important difference (MCID) following traction supporting the validity of this test.

  9. Prehabilitation and rehabilitation for attenuating hindlimb unweighting effects on skeletal muscle and gait in adult and old rats. (United States)

    Brown, Marybeth; Taylor, Jennifer


    To compare the effectiveness of no exercise with prehabilitation (exercise before hindlimb unweighting [HLU]) versus rehabilitation (exercise given after HLU) on gait function and skeletal muscle mass and force. Randomized controlled trial. Animal laboratory. Male-specific, pathogen-free Fisher344/Brown Norway rats (N=149). Groups consisted of adult and old controls, HLU, prehabilitation, rehabilitation, natural cage recovery (reloading), and exercise without HLU. Ten days of general conditioning exercise were given to 6-month-old adult and 30-month-old old rats before or after a week of HLU. Gait stride length and width; soleus, plantaris, extensor digitorum longus, and peroneus longus mass and peak contractile force; whole gastrocnemius mass; and total protein concentration for the soleus and gastrocnemius. Muscle mass (approximately 30%) and force (24%-36%) declined with age in all muscles studied. In adult rats declines in muscle mass occurred with HLU in the soleus, plantaris, and gastrocnemius. Prehabilitation did not prevent the loss of muscle mass in adult rats. Rehabilitation and natural recovery effectively restored soleus and gastrocnemius muscle mass in adult rats but not soleus peak force. Old rats had a significant 23% HLU effect only on gastrocnemius mass (control, 1670+/-129 mg; HLU, 1274+/-184 mg). Prehabilitation did not prevent the decline in gastrocnemius mass. Rehabilitation in old rats restored gastrocnemius mass to within 13% of control levels. Prehabilitation was effective for preventing and rehabilitation was effective for restoring soleus contractile force in old rats (control, 114+/-9 mg; HLU, 67+/-22 mg; prehabilitation, 106+/-31 mg; rehabilitation, 120+/-26 mg) compared with recovery without exercise (86+/-29 g). A significant reduction in stride length was observed with aging (136+/-18 mm vs 98+/-10 mm), which decreased further with HLU (78+/-14 mm). Prehabilitation attenuated HLU-related reductions in stride length, and rehabilitation

  10. Photodynamic Therapy Mediated by Upconversion Nanoparticles to Reduce Glial Scar Formation and Promote Hindlimb Functional Recovery After Spinal Cord Injury in Rats. (United States)

    Liu, Yang; Ban, De-Xiang; Ma, Chao; Zhang, Zhi-Guo; Zhang, Jia-Yin; Gao, Shi-Jie; Feng, Shi-Qing


    Glial scar formation is one of the major consequences of spinal cord injury, which prevents the regenerated axons passing the injured area and forming effective synaptic connection. In this paper, we used photodynamic therapy (PDT), which was mediated by the upconversion nanoparticles coated with polyethylene glycol (PEG) and photosensitizer (UCNPs-PEGM540), to reduce the glial scar formation after spinal cord injury. The in vitro experimental results indicated that cultured astrocytes could be killed by using upconversion nanoparticles after excitation with near infrared light. By transplanting UCNPs-PEG-M540 into the margin area of injured epicenter of spinal cord, the recovery of rat's hindlimb function was evaluated in Basso, Beattie, Bresnahan locomotor rating scale, respectively. The improvement in microenvironment of the injured spinal cord was also evaluated by glial fibrillary acidic protein staining, neurofiliment staining, biotinylated dextran amine anterograde tracing and western blotting. Our results demonstrated that more regenerative axons of corticospinal tract were found to surround and pass through the injured cavity to the caudal cord with transplanting UCNPs-PEG-M540 into the injured spinal cord. In conclusion, our results strongly suggested that upconversion nanoparticles combined with photodynamic therapy can promote functional recovery in rats' hindlimbs by reducing the formation of glial scar and promoting remyelination of injured axons.

  11. A preliminary assessment of a novel pneumatic unloading knee brace on the gait mechanics of patients with knee osteoarthritis. (United States)

    Della Croce, Ugo; Crapanzano, Fausto; Li, Ling; Kasi, Patrick K; Patritti, Benjamin L; Mancinelli, Chiara; Hunter, David J; Stamenović, Dimitrije; Harvey, William F; Bonato, Paolo


    To determine whether a knee brace incorporating inflatable air bladders can alter the net peak external knee adduction moment in persons with medial compartment knee osteoarthritis. Prospective cohort study. Motion analysis laboratory. Subjects (n = 18) diagnosed with knee osteoarthritis as defined by the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Instrumented gait analysis was performed while subjects walked with and without the knee brace. When subjects wore the knee brace, the air bladders were either uninflated or inflated to 7 psi. The net external knee adduction moment was obtained by subtracting the abduction moment produced by the knee brace (estimated using a finite element analysis model) from the external knee adduction moment (estimated using a camera-based motion analysis system). The net external knee adduction moment was compared across all testing conditions. A 7.6% decrease in net peak external knee adduction moment was observed when subjects wore the knee brace uninflated compared with when they did not wear the brace. Inflation of the bladders to 7 psi led to a 26.0% decrease in net peak external knee adduction moment. The results of the study suggest that the effects of an unloading knee brace may be enhanced by incorporating inflatable air bladders into the design of the brace, thus leading to an improved correction of the excessive peak external knee adduction moment observed in patients with medial compartment knee osteoarthritis. Copyright © 2013. Published by Elsevier Inc.

  12. Effects of loading–unloading and wetting–drying cycles on geomechanical behaviors of mudrocks in the Colombian Andes

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    Mario Camilo Torres-Suarez


    Full Text Available The mudrocks in the Colombian Andes, particularly those exhibiting low cementation (bonding, are susceptible to degradation when the environmental conditions change, which are challenging issues for engineering works. In this paper, the changes in physico-mechanical properties of mudrocks were monitored in laboratory, and some influential factors on the mechanical competence of geomaterials were studied. The geotechnical characteristics and experimental designs were developed from physical, chemical, mechanical and compositional points of view. In the tests, the techniques such as vapor equilibrium technique (VET were employed to apply wetting–drying cycles and to control relative humidity (suction-controlled and loading–unloading cycles through ultrasonic wave velocities technique. The results show that the main failure mechanisms for the laminated mudrocks start on the microscopic scale by fissures coalescence, exhibiting physico-chemical degradation as well; the global geomechanical behavior presents a state between a ductile, like rock, and a fragile, like soil. The obtained results can provide engineering values according to monitoring laboratory set, when compared with in situ conditions.

  13. Tehnološko projektovanje pretovarno-skladišnih procesa / Technological design of loading/unloading and warehousing processes

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    Momčilo Miljuš


    Full Text Available Tehnološko projektovanje logističkih sistema karakteriše veoma visok stepen kompleksnosti, a od njegovog kvaliteta u znatnoj meri zavisi i efikasnost i ekonomičnost realizacije logističkih procesa u praksi. Pretovarno-skladišne procese (PSP u okviru odgovarajućih logističkih podsistema, a posebno u okviru realizacije tokova materijala, karakteriše niz specifičnosti koje u znatnoj meri usložavaju tipične PSP. Da bi se ostvarili preduslovi za adekvatno realizovanje PSP, u ovom radu je dat pregled metodologije tehnološkog projektovanja ovih sistema. / Design of technological processes is one of the most complex tasks in the field of design in general. This type of design is also involved in logistic system design as these systems are typically very complex so that quality of design solution has a great influence on efficiency and economical level of logistic processes efficiency in practice. Loading/unloading and warehousing processes (LUWP within some logistics systems, especially in material flows require specific efforts which complicate typical LUWP. Aiming to consider adequate realization of LUWP, this paper shows the methodology of design of these systems.

  14. Noninvasive continuous versus intermittent arterial pressure monitoring: evaluation of the vascular unloading technique (CNAP device) in the emergency department. (United States)

    Wagner, Julia Y; Prantner, Julia S; Meidert, Agnes S; Hapfelmeier, Alexander; Schmid, Roland M; Saugel, Bernd


    Monitoring cardiovascular function in acutely ill patients in the emergency department (ED) is of paramount importance. Arterial pressure (AP) is usually monitored using intermittent oscillometric measurements with an upper arm cuff. The vascular unloading technique (VUT) allows continuous noninvasive AP monitoring. In this study, we compare continuous AP measurements obtained by VUT with intermittent oscillometric AP measurements in ED patients. In addition, we aimed to investigate whether continuous noninvasive AP monitoring allows detection of relevant hypotensive episodes that might be missed with intermittent AP monitoring. In a German university hospital, 130 ED patients who required AP monitoring were analyzed in this prospective method comparison study. Continuous AP monitoring was performed using VUT (CNAP technology; CNSystems Medizintechnik AG, Graz, Austria) over a 2-hour period. The oscillometric AP values were recorded simultaneously every 15 minutes for the comparison of both methods. For statistical evaluation, Bland-Altman plots accounting for repeated AP measurements per individual were used. The mean difference (±standard deviation) between AP measurements obtained by VUT and oscillometric AP measurements was -5 mmHg (±22 mmHg) for systolic AP (SAP), -2 mmHg (±15 mmHg) for diastolic AP (DAP), and -6 mmHg (±16 mmHg) for mean AP (MAP), respectively. In the interval between two oscillometric measurements, the VUT device detected hypotensive episodes (≥4 minutes) defined as either SAP monitoring allows immediate recognition of clinically relevant hypotensive episodes, which are missed or only belatedly recognized with intermittent AP measurement.

  15. Control of Genome Integrity by RFC Complexes; Conductors of PCNA Loading onto and Unloading from Chromatin during DNA Replication

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    Yasushi Shiomi


    Full Text Available During cell division, genome integrity is maintained by faithful DNA replication during S phase, followed by accurate segregation in mitosis. Many DNA metabolic events linked with DNA replication are also regulated throughout the cell cycle. In eukaryotes, the DNA sliding clamp, proliferating cell nuclear antigen (PCNA, acts on chromatin as a processivity factor for DNA polymerases. Since its discovery, many other PCNA binding partners have been identified that function during DNA replication, repair, recombination, chromatin remodeling, cohesion, and proteolysis in cell-cycle progression. PCNA not only recruits the proteins involved in such events, but it also actively controls their function as chromatin assembles. Therefore, control of PCNA-loading onto chromatin is fundamental for various replication-coupled reactions. PCNA is loaded onto chromatin by PCNA-loading replication factor C (RFC complexes. Both RFC1-RFC and Ctf18-RFC fundamentally function as PCNA loaders. On the other hand, after DNA synthesis, PCNA must be removed from chromatin by Elg1-RFC. Functional defects in RFC complexes lead to chromosomal abnormalities. In this review, we summarize the structural and functional relationships among RFC complexes, and describe how the regulation of PCNA loading/unloading by RFC complexes contributes to maintaining genome integrity.

  16. Plantar flexor stretch reflex responses to whole body loading/unloading during human walking

    DEFF Research Database (Denmark)

    Grey, Michael James; van Doornik, Johannes; Sinkjær, Thomas


    perturbation during human walking. Three body load conditions were investigated: normal body load, a 30% increase in body load, and a 30% decrease in body load. Healthy subjects walked on a treadmill at approximately 3.6 km/h with the left ankle attached to a portable stretching device. Dorsiflexion......Numerous animal and human studies have shown that afferent information from the periphery contributes to the control of walking. In particular, recent studies have consistently shown that load receptor input is an important element of the locomotion control mechanism. The objective of this study...... electrodes. Stretch reflex responses were observed in the soleus and gastrocnemius muscles for all of the body load conditions; however, increasing or decreasing the body load did not affect the timing and magnitude of the responses. This study provides evidence that load receptor input does not contribute...

  17. Study of the influence of the operation of the unloading facility on the hydraulic conditions in the installation for dry quenching of coke

    Energy Technology Data Exchange (ETDEWEB)

    Grishchenko, A.I.; Ereskovskii, O.S.; Lavrishchev, V.I.


    Theoretical studies are presented elucidating the occurrence of a dislocation of the normal pressure distribution along the circuit of the installation for dry quenching of coke in dependence on the conditions of operation of the unloading facility. An electrical model is proposed for the hydraulic conditions in the installation for dry quenching of coke, allowing a study of the aerodynamic conditions of operation of the installation to be performed on an analog computer with sufficient accuracy.

  18. Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury in Mice. (United States)

    Takahashi, Hiroshi; Koda, Masao; Hashimoto, Masayuki; Furuya, Takeo; Sakuma, Tsuyoshi; Kato, Kei; Okawa, Akihiko; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Maki, Satoshi; Takahashi, Kazuhisa; Yamazaki, Masashi; Mannoji, Chikato


    Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 µl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 10(5)/µl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 10(5)/µl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration

  19. Unloading and reloading working memory: attending to one item frees capacity. (United States)

    Souza, Alessandra S; Rerko, Laura; Oberauer, Klaus


    During the retention interval of a working memory task, presenting a retro-cue directs attention to 1 of the items in working memory. Testing the cued item leads to faster and more accurate responses. We contrasted 5 explanations of this benefit: (a) removal of noncued items, (b) strengthening of the cued item, (c) protection from probe interference, (d) protection from degradation, and (e) prioritization during the decision process. Experiment 1 showed that retro-cues reduced the set size effect in a visual recognition task, and did so increasingly with more time available to use the retro-cue. This finding is predicted only by Hypotheses 1 and 2. Hypotheses 3 through 5 were ruled out as explanations of the retro-cue benefit in this experiment. In Experiments 2 and 3, participants encoded 2 sequentially presented memory sets. In half of the trials, 1 item from the first set was retro-cued during the interset interval. Retro-cues improved memory for the second set. This reloading benefit is predicted only by the removal hypothesis: Irrelevant contents are removed from working memory, freeing capacity to encode new contents. Experiment 3 also yielded evidence that strengthening of the cued item might contribute to the retro-cue effect. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  20. Feasibility Study For Use Of Commercial Cask Vendor Dry Transfer Systems To Unload Used Fuel Assemblies In L-Area

    Energy Technology Data Exchange (ETDEWEB)

    Krementz, Dan [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Rose, David [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Dunsmuir, Mike [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)


    The purpose of this study is to determine whether a commercial dry transfer system (DTS) could be used for loading or unloading used nuclear fuel (UNF) in L-Basin and to determine if a DTS pool adapter could be made for L-Basin Transfer Pit #2 that could accommodate a variety of DTS casks and fuel baskets or canisters up to 24” diameter.[1, 2] This study outlines the technical feasibility of accommodating different vendor dry transfer systems in the L-Basin Transfer Bay with a general work scope. It identifies equipment needing development, facility modifications, and describes the needed analyses and calculations. After reviewing the L-Basin Transfer Bay area layout and information on the only DTS system currently in use for the Nuclear Assurance Corporation Legal Weight Truck cask (NAC LWT), the authors conclude that use of a dry transfer cask is feasible. AREVA was contacted and acknowledged that they currently do not have a design for a dry transfer cask for their new Transnuclear Long Cask (TN-LC) cask. Nonetheless, this study accounted for a potential future DTS from AREVA to handle fuel baskets up to 18” in diameter. Due to the layout of the Transfer Bay, it was determined that a DTS cask pool adapter designed specifically for spanning Pit #2 and placed just north of the 70 Ton Cask lid lifting superstructure would be needed. The proposed pool adapter could be used to transition a fuel basket up to 24” in diameter and ~11 feet long from a dry transfer cask to the basin. The 18” and 24” applications of the pool adapter are pending vendor development of dry transfer casks that accommodate these diameters. Once a fuel basket has been lowered into Pit #2 through a pool adapter, a basket cart could be used to move the basket out from under the pool adapter for access by the 5 Ton Crane. The cost to install a dry transfer cask handling system in L-Area capable of handling multiple vendor provided transport and dry transfer casks and baskets with

  1. Noninvasive continuous versus intermittent arterial pressure monitoring: evaluation of the vascular unloading technique (CNAP device) in the emergency department (United States)


    Background Monitoring cardiovascular function in acutely ill patients in the emergency department (ED) is of paramount importance. Arterial pressure (AP) is usually monitored using intermittent oscillometric measurements with an upper arm cuff. The vascular unloading technique (VUT) allows continuous noninvasive AP monitoring. In this study, we compare continuous AP measurements obtained by VUT with intermittent oscillometric AP measurements in ED patients. In addition, we aimed to investigate whether continuous noninvasive AP monitoring allows detection of relevant hypotensive episodes that might be missed with intermittent AP monitoring. Methods In a German university hospital, 130 ED patients who required AP monitoring were analyzed in this prospective method comparison study. Continuous AP monitoring was performed using VUT (CNAP technology; CNSystems Medizintechnik AG, Graz, Austria) over a 2-hour period. The oscillometric AP values were recorded simultaneously every 15 minutes for the comparison of both methods. For statistical evaluation, Bland-Altman plots accounting for repeated AP measurements per individual were used. Results The mean difference (±standard deviation) between AP measurements obtained by VUT and oscillometric AP measurements was -5 mmHg (±22 mmHg) for systolic AP (SAP), -2 mmHg (±15 mmHg) for diastolic AP (DAP), and -6 mmHg (±16 mmHg) for mean AP (MAP), respectively. In the interval between two oscillometric measurements, the VUT device detected hypotensive episodes (≥4 minutes) defined as either SAP oscillometric AP measurement. Conclusions VUT using the CNAP system for noninvasive continuous AP measurement shows reasonable agreement with intermittent oscillometric measurements in acutely ill ED patients. Continuous AP monitoring allows immediate recognition of clinically relevant hypotensive episodes, which are missed or only belatedly recognized with intermittent AP measurement. PMID:24472659

  2. Power variables and bilateral force differences during unloaded and loaded squat jumps in high performance alpine ski racers. (United States)

    Patterson, Carson; Raschner, Christian; Platzer, Hans-Peter


    The purpose of this paper was to investigate the power-load relationship and to compare power variables and bilateral force imbalances between sexes with squat jumps. Twenty men and 17 women, all members of the Austrian alpine ski team (junior and European Cup), performed unloaded and loaded (barbell loads equal to 25, 50, 75, and 100% body weight [BW]) squat jumps with free weights using a specially designed spotting system. Ground reaction force records from 2 force platforms were used to calculate relative average power (P), relative average power in the first 100 ms of the jump (P01), relative average power in the first 200 ms of the jump (P02), jump height, percentage of best jump height (%Jump), and maximal force difference between dominant and nondominant leg (Fmaxdiff). The men displayed significantly higher values at all loads for P and jump height (p < 0.05). No significant differences were found in P01. The men had significantly higher P02 at all loads except 75% BW). Maximum P was reached at light loads (men at 25% BW and women at 0% BW), and P decreased uniformly thereafter. Individual power-load curves show a deflection point. It is proposed that the load where the power-load deflection point occurs be used as the power training load and not the load at which maximum P is reached. It is also proposed that loads not be described in %1-repetition maximum (RM), but as %BW. This system can be used to safely assess and train power with loaded jumps and free weights.

  3. The effusive-explosive transitions at Rokatenda 2012-2013: unloading by extrusion of degassed magma with lateral gas flow (United States)

    Primulyana, Sofyan; Bani, Philipson; Harris, Andrew


    Between October 2012 and August 2013, Rokatenda, one of the most poorly understood volcanoes in Indonesia, entered a phase of intense eruptive activity which involved extrusion of viscous lava, gas discharge and explosive activity. During the 10-month-long eruption, a lava volume of 2-5 × 106 m3 was extruded at mean output rate of 0.3 m3 s-1, with 2 to 3-month-long high extrusion rate phases being terminated by explosive events. Extrusion built a lava dome attaining a maximum height of ˜80 m above the crater rim, with a basal width of about 250 m. The composition of the 2012-2013 lava dome is comparable to that of the 1980 lava dome, both being andesite-trachydacite. Mineralogically, the 2012-2013 lava dome is mainly composed of plagioclase, pyroxene and an undetermined opaque mineral. Halogens released during eruption are consistent with the extrusion being fed, at least in the first eruption phase, by a degassed magma. This resulted in the formation of a dense, viscous plug in the conduit that led to a lateral gas flow, with gasses escaping around the plug to form multiple craters surrounding the dome. During the course of the eruptive activity, degassed magma was progressively forced out of the vent to unload deeper magma and force the system into an explosive phase. Such a scenario has occurred in the past at Rokatenda and is likely to be repeated in the future and creates an activity pattern that may be used to characterize such systems.

  4. From the international space station to the clinic: how prolonged unloading may disrupt lumbar spine stability. (United States)

    Bailey, Jeannie F; Miller, Stephanie L; Khieu, Kristine; O'Neill, Conor W; Healey, Robert M; Coughlin, Dezba G; Sayson, Jojo V; Chang, Douglas G; Hargens, Alan R; Lotz, Jeffrey C


    : -17.3%, p=0.016; L4-L5: -30.3%, p=0.004). By contrast, no significant passive FE ROM changes in these discs were observed (p>0.05). Disc water content did not differ systematically from pre- to post-flight. Multifidus and erector spinae changed variably between subjects, with five of six subjects experiencing an average decrease 20% for FCSA and 8-9% for CSA in both muscles. For all subjects, changes in multifidus FCSA strongly correlated with changes in lordosis (r(2)=0.86, p=0.008) and active FE ROM at L4-L5 (r(2)=0.94, p=0.007). Additionally, changes in multifidus FCSA/CSA correlated with changes in lordosis (r(2)=0.69, p=0.03). While multifidus-associated changes in lordosis and ROM were present amongst all subjects, only those with severe, pre-flight endplate irregularities (2 of 6 subjects) had post-flight lumbar symptoms (including chronic low back pain or disc herniation). Conclusions We observed that multifidus atrophy, rather than intervertebral disc swelling, associated strongly with lumbar flattening and increased stiffness. Because these changes have been previously linked with detrimental spine biomechanics and pain in terrestrial populations, when combined with evidence of pre-flight vertebral endplate insufficiency, they may elevate injury risk for astronauts upon return to gravity loading. Our results also have implications for deconditioned spines on Earth. We anticipate that our results will inform new astronaut countermeasures that target the multifidus muscles, and research on the role of muscular stability in relation to chronic low back pain and disc injury. Copyright © 2017. Published by Elsevier Inc.

  5. Knee braces - unloading (United States)

    ... most people talk about the arthritis in their knees, they are referring to a type of arthritis ... is caused by wear and tear inside your knee joints. Cartilage, the firm, rubbery tissue that cushions ...

  6. Members of the flight and ground crews prepare to unload equipment from NASA's B377SGT Super Guppy T (United States)


    Members of the flight and ground crews prepare to unload equipment from NASA's B377SGT Super Guppy Turbine cargo aircraft on the ramp at NASA's Dryden Flight Research Center at Edwards Air Force Base, Calif. The outsize cargo plane had delivered the latest version of the X-38 flight test vehicle to NASA Dryden when this photo was taken on June 11, 2000. The B-377SGT Super Guppy Turbine evolved from the 1960s-vintage Pregnant Guppy, Mini Guppy and Super Guppy, used for transporting sections of the Saturn rocket used for the Apollo program moon launches and other outsized cargo. The various Guppies were modified from 1940's and 50's-vintage Boeing Model 377 and C-97 Stratocruiser airframes by Aero Spacelines, Inc., which operated the aircraft for NASA. NASA's Flight Research Center assisted in certification testing of the first Pregnant Guppy in 1962. One of the turboprop-powered Super Guppies, built up from a YC-97J airframe, last appeared at Dryden in May, 1976 when it was used to transport the HL-10 and X-24B lifting bodies from Dryden to the Air Force Museum at Wright-Patterson Air Force Base, Ohio. NASA's present Super Guppy Turbine, the fourth and last example of the final version, first flew in its outsized form in 1980. It and its three sister ships were built in the 1970s for Europe's Airbus Industrie to ferry outsized structures for Airbus jetliners to the final assembly plant in Toulouse, France. It later was acquired by the European Space Agency, and then acquired by NASA in late 1997 for transport of large structures for the International Space Station to the launch site. It replaced the earlier-model Super Guppy, which has been retired and is used for spare parts. NASA's Super Guppy Turbine carries NASA registration number N941NA, and is based at Ellington Field near the Johnson Space Center. For more information on NASA's Super Guppy Turbine, log onto the Johnson Space Center Super Guppy web page at

  7. Descargas de cascarilla de soja en Tarragona y riesgo de epidemias de asma Soybean hull unloading in Tarragona (Spain and asthma outbreak risk

    Directory of Open Access Journals (Sweden)

    Enric Rovira


    Full Text Available Objetivos: Entre 2007 y 2008 se descargaron 215.000 toneladas de cascarilla de soja en el puerto de Tarragona. En la cascarilla se encuentra la proteína causante de las epidemias de asma bronquial. Los objetivos de este estudio fueron estudiar las características de las descargas, la dispersión del alergeno y el riesgo para la población. Métodos: Se recogió información sobre el proceso de descarga, transporte y almacenaje, la meteorología y los casos de asma atendidos en urgencias hospitalarias. Se midió la concentración de alergeno en los filtros de PM10 de las estaciones de vigilancia de la contaminación atmosférica. En los pacientes sensibilizados se realizó un estudio clínico consistente en pruebas cutáneas, IgE sérica total y específica para soja, e inmunoblotting. Resultados: Se encontraron concentraciones moderadas de alergeno a un kilómetro del punto de descarga (3 días por encima de 300U/m³, máximo 441U/m³. El perfil proteico de los extractos de cascarilla es similar al de las muestras de las epidemias de Barcelona. El 92% de los pacientes estudiados son sensibles a los extractos de cascarilla. No hubo ninguna epidemia de asma durante los días de descarga. Además de las proteínas de bajo peso molecular identificadas en estudios anteriores (6 y 14-17kDa, se han encontrado proteínas de mayor peso molecular (14-49kDa. Conclusiones: Existe dispersión del alergeno a corta distancia del lugar de la descarga y riesgo para la población que continúa sensibilizada. Han de adoptarse medidas durante las descargas para reducir al mínimo la emisión de partículas.Objectives: From 2007 to 2008, 215,000 tons of soybean hull were unloaded in the Port of Tarragona. Soybean hull was identified as the etiologic agent causing bronchial asthma outbreaks. The aim of the present study was to identify the characteristics of soybean unloading, soybean allergen dispersion, and the population risk. Methods: Data on soybean hull


    Directory of Open Access Journals (Sweden)

    V. N. Poptsov


    Full Text Available Aim. Peripheral VA ECMO is effective method of circulatory support in heart transplant candidates with life th- reatening CHF. However this type of extracorporeal life support may be complicated by pulmonary congestion (“white lung” as a result of left ventricle (LV dilatation and volume overload. Difference approach proposed for LV unloading following VA ECMO circulatory support. We report our experience of LV unloading by percutaneous introduced of supplement drainage cannula in the left atrium (LA through the femoral vena and interatrial septum. Material and methods. In this study was included 33 heart transplant candidates (6/27 F/M, age 46.2 ± 3.7 yrs on peripheral VA ECMO support. For LV unloading we used supplement standard venous ECMO-cannula (15–19 F percutaneous introduced in LA through the femoral vena of conterlateral leg and connected to the venous line of ECMO circuit. Results. To 20 (60.6% from 33 patients needed of early (n = 10 or delayed (n = 10 LA drainage. After beginning of LV drainage we noted of significant (p < 0.05 decreasing of PAWP from 31 ± 3 to 14 ± 3 mm Hg and resolution of pulmonary edema. Mean blood flow on LA cannula was 1.5 ± 0.2 l/min. To 18 (90% from 20 patients was successfully bridged to heart transplantation. Duration VA ECMO before OHT was 8.6 ± 1.7 days. 16 (88.9% recipients were discharged from hospital. Conclusion. Active LA drainage is as effective tool of LV un- loading and protection of pulmonary congestion and edema in patients bridged to heart transplantation by peripheral VA ECMO. 

  9. Relation Between Pressure and Volume Unloading During Ramp Testing in Patients Supported with a Continuous-Flow Left Ventricular Assist Device

    DEFF Research Database (Denmark)

    Jung, Mette H; Hassager, Christian; Balling, Louise


    Pulmonary capillary wedge pressure (PCWP) is the key to describing left ventricular (LV) unloading, however, the relation between pressure and the echocardiography-derived surrogate of LV volume (left ventricular end-diastolic diameter (LVEDD)) as a function of pump speed (RPM) in continuous......-flow left ventricular assist device (CF-LVAD) patients is unknown. In this study the pressure-volume relationship as a function of RPM during ramp testing was investigated by simultaneously measuring PCWP by Swan-Ganz catheter and LVEDD by echocardiography. The ramp protocol started at usual pump setting...

  10. Green tea extract attenuates muscle loss and improves muscle function during disuse, but fails to improve muscle recovery following unloading in aged rats (United States)

    Bennett, Brian T.; Wilson, Joseph C.; Sperringer, Justin; Mohamed, Junaith S.; Edens, Neile K.; Pereira, Suzette L.


    In this study we tested the hypothesis that green tea extract (GTE) would improve muscle recovery after reloading following disuse. Aged (32 mo) Fischer 344 Brown Norway rats were randomly assigned to receive either 14 days of hindlimb suspension (HLS) or 14 days of HLS followed by normal ambulatory function for 14 days (recovery). Additional animals served as cage controls. The rats were given GTE (50 mg/kg body wt) or water (vehicle) by gavage 7 days before and throughout the experimental periods. Compared with vehicle treatment, GTE significantly attenuated the loss of hindlimb plantaris muscle mass (−24.8% vs. −10.7%, P muscle function or mass compared with vehicle treatment, animals given green tea via gavage maintained the lower losses of muscle mass that were found during HLS (−25.2% vs. −16.0%, P muscle fiber cross-sectional area loss in both plantaris (−39.9% vs. −23.9%, P muscles after HLS. This green tea-induced difference was not transient but was maintained over the reloading period for plantaris (−45.6% vs. −21.5%, P muscle fiber cross-sectional area (−38.7% vs. −10.9%, P muscles during recovery from HLS compared with vehicle-treated muscles and decreased oxidative stress and abundance of the Bcl-2-associated X protein (Bax), yet this did not further improve muscle recovery in reloaded muscles. These data suggest that muscle recovery following disuse in aging is complex. Although satellite cell proliferation and differentiation are critical for muscle repair to occur, green tea-induced changes in satellite cell number is by itself insufficient to improve muscle recovery following a period of atrophy in old rats. PMID:25414242

  11. Design and construction of coal unloading pier for Tachibana Bay Coal-fired Power Station; Tachibanawan sekitan karyoku hatsudensho yotan sanbashi no sekkei to seko

    Energy Technology Data Exchange (ETDEWEB)

    Tada, K.; Sudo, T. [Electric Power Development Co. Ltd., Tokyo (Japan)


    Tachibana Bay Coal-fired Power Station located at Kokatsu Island in Tachibana Bay, Anan City, Tokushima Prefecture, Japan is a power station with a power output 2.8 million kW constructed jointly by Electric Power Development Co., Ltd. and Shikoku Electric Power Co., Inc. Civil works were started in March, 1995. Construction works are carried out for the operation start of No.1 Unit of Shikoku Electric Power Co., Inc. and Electric Power Development Co., Ltd. in July, 2000 and for the operation start of No.2 Unit of Electric Power Development Co., Ltd. in January, 2001. This paper describes an outline of design and construction of a coal unloading pier for the Tachibana Bay Coal-fired Power Station. For the design calculation, loads of unloaders which have a weight over 1,000 tons per unit are dominant on the pier. To endure the horizontal force during earthquake, steel pipe piles with a diameter 1,600 mm were used for the foundation, and RC girder slabs were used for the superstructure. This is called a straight pile-type pier structure. To avoid corrosion of steel piles, FRP cover and polyethylene coating were adopted depending on the place. Electric anticorrosion was adopted in the sea water and sea soil. Placing works of a total of 541 steel pipe piles including 300 piles with a diameter 1,600 mm were successfully completed for 12 months. 4 refs., 3 figs., 1 tab.

  12. Do laterally wedged insoles or valgus braces unload the medial compartment of the knee in patients with osteoarthritis? (United States)

    Duivenvoorden, Tijs; van Raaij, Tom M; Horemans, Herwin L D; Brouwer, Reinoud W; Bos, P Koen; Bierma-Zeinstra, Sita M A; Verhaar, Jan A N; Reijman, Max


    differences in biomechanical effect for obesity, stage of OA, and whether patients showed a clinical response to the treatment. Laterally wedged insoles unload the medial compartment only at baseline in patients with varus alignment and by an amount that might not be clinically important. No biomechanical alteration was seen after 6 weeks of wearing the insole. Valgus brace therapy did not result in any biomechanical alteration. Taken together, this study does not show a clinically relevant biomechanical effect of insole and brace therapy in patients with varus medial knee OA. Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

  13. Hypoxia pretreatment of bone marrow-derived mesenchymal stem cells seeded in a collagen-chitosan sponge scaffold promotes skin wound healing in diabetic rats with hindlimb ischemia. (United States)

    Tong, Chuan; Hao, Haojie; Xia, Lei; Liu, Jiejie; Ti, Dongdong; Dong, Liang; Hou, Qian; Song, Haijing; Liu, Huiling; Zhao, Yali; Fu, Xiaobing; Han, Weidong


    Bone marrow-derived mesenchymal stem cells (BM-MSCs) have properties that make them promising for the treatment of chronic nonhealing wounds. The major challenge is ensuring an efficient, safe, and painless delivery of BM-MSCs. Tissue-engineered skin substitutes have considerable benefits in skin damage resulting from chronic nonhealing wounds. Here, we have constructed a three-dimensional biomimetic scaffold known as collagen-chitosan sponge scaffolds (CCSS) using the cross-linking and freeze-drying method. Scanning electron microscopy images showed that CCSS had an interconnected network pore configuration about 100 μm and exhibited a suitable swelling ratio for maintaining morphological stability and appropriate biodegradability to improve biostability using swelling and degradation assays. Furthermore, BM-MSCs were seeded in CCSS using the two-step seeding method to construct tissue-engineered skin substitutes. In addition, in this three-dimensional biomimetic CCSS, BM-MSCs secreted their own collagen and maintain favorable survival ability and viability. Importantly, BM-MSCs exhibited a significant upregulated expression of proangiogenesis factors, including HIF-1α, VEGF, and PDGF following hypoxia pretreatment. In vivo, hypoxia pretreatment of the skin substitute observably accelerated wound closure via the reduction of inflammation and enhanced angiogenesis in diabetic rats with hindlimb ischemia. Thus, hypoxia pretreatment of the skin substitutes can serve as ideal bioengineering skin substitutes to promote optimal diabetic skin wound healing. © 2015 by the Wound Healing Society.

  14. Interactive 3D Analysis of Blood Vessel Trees and Collateral Vessel Volumes in Magnetic Resonance Angiograms in the Mouse Ischemic Hindlimb Model. (United States)

    Marks, Peter C; Preda, Marilena; Henderson, Terry; Liaw, Lucy; Lindner, Volkhard; Friesel, Robert E; Pinz, Ilka M


    The quantitative analysis of blood vessel volumes from magnetic resonance angiograms (MRA) or μCT images is difficult and time-consuming. This fact, when combined with a study that involves multiple scans of multiple subjects, can represent a significant portion of research time. In order to enhance analysis options and to provide an automated and fast analysis method, we developed a software plugin for the ImageJ and Fiji image processing frameworks that enables the quick and reproducible volume quantification of blood vessel segments. The novel plugin named Volume Calculator (VolCal), accepts any binary (thresholded) image and produces a three-dimensional schematic representation of the vasculature that can be directly manipulated by the investigator. Using MRAs of the mouse hindlimb ischemia model, we demonstrate quick and reproducible blood vessel volume calculations with 95 - 98% accuracy. In clinical settings this software may enhance image interpretation and the speed of data analysis and thus enhance intervention decisions for example in peripheral vascular disease or aneurysms. In summary, we provide a novel, fast and interactive quantification of blood vessel volumes for single blood vessels or sets of vessel segments with particular focus on collateral formation after an ischemic insult.

  15. Adeno-associated viral vector-mediated neurotrophin gene transfer in the injured adult rat spinal cord improves hind-limb function. (United States)

    Blits, B; Oudega, M; Boer, G J; Bartlett Bunge, M; Verhaagen, J


    To foster axonal growth from a Schwann cell bridge into the caudal spinal cord, spinal cells caudal to the implant were transduced with adeno-associated viral (AAV) vectors encoding for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (AAV-NT-3). Control rats received AAV vectors encoding for green fluorescent protein or saline. AAV-BDNF- and AAV-NT-3-transduced 293 human kidney cells produced and secreted BDNF or NT-3, respectively, in vitro. The secreted neurotrophins were biologically active; they both promoted outgrowth of sensory neurites in vitro. In vivo, transgene expression was observed predominantly in neurons for at least 16 weeks after injection. Compared with controls, a modest though significant improvement in hind-limb function was found in rats that received AAV-BDNF and AAV-NT-3. Retrograde tracing demonstrated that twice as many neurons with processes extending toward the Schwann cell graft were present in the second lumbar cord segment of AAV-BDNF- and AAV-NT-3-injected animals compared with controls. We found no evidence, however, for growth of regenerated axons from the Schwann cell implant into the caudal cord. Our results suggest that AAV vector-mediated overexpression of BDNF and NT-3 in the cord caudal to a Schwann cell bridge modified the local lumbar axonal circuitry, which was beneficial for locomotor function.

  16. Effects of varying patterns of external compression on lymph flow in the hindlimb of the anaesthetized sheep. (United States)

    McGeown, J G; McHale, N G; Thornbury, K D


    1. Lymphatics draining the region distal to the fetlock were cannulated in anaesthetized sheep. A pneumatic cuff was used to intermittently compress the drainage area. 2. Intermittent inflation of the cuff accelerated lymph flow. This effect increased dramatically as the frequency of inflation was increased. 3. With a constant inflation time, increasing the time between inflations increased the additional volume of lymph expelled per external compression threefold over the range of 0.5-8 s. Longer intervals produced little further change. 4. There was no significant difference between the effects on lymph volume per compression of intermittent cuff inflations lasting from 1 to 18 s with a constant time between inflations. 5. A cuff pressure of 20 mmHg produced a significant rise in lymph flow. Increasing the pressure applied during cuff inflation increased the effect up to the maximum pressure used (320 mmHg). 6. These studies demonstrate that the promotion of lymph formation by tissue compression is related to the number of compressions applied and the period of time between them. Increasing the pressure exaggerates the effect but increasing the length of each compression does not. This suggests that compression empties the terminal lymphatics centripetally. These vessels refill after compression is released and in our preparation this is complete in about 8 s. PMID:3411513

  17. In vivo longitudinal study of rodent skeletal muscle atrophy using ultrasonography


    Antonietta Mele; Adriano Fonzino; Francesco Rana; Giulia Maria Camerino; Michela De Bellis; Elena Conte; Arcangela Giustino; Diana Conte Camerino; Jean-François Desaphy


    Muscle atrophy is a widespread ill condition occurring in many diseases, which can reduce quality of life and increase morbidity and mortality. We developed a new method using non-invasive ultrasonography to measure soleus and gastrocnemius lateralis muscle atrophy in the hindlimb-unloaded rat, a well-accepted model of muscle disuse. Soleus and gastrocnemius volumes were calculated using the conventional truncated-cone method and a newly-designed sinusoidal method. For Soleus muscle, the ultr...

  18. Unloaded movement facilitation exercise compared to no exercise or alternative therapy on outcomes for people with nonspecific chronic low back pain: a systematic review. (United States)

    Slade, Susan C; Keating, Jennifer L


    The purpose of this study was to determine the effect of unloaded movement facilitation exercises on outcomes for people with nonspecific chronic low back pain (NSCLBP). This systematic review was conducted according to Cochrane Back Review Group and Quality of Reporting of Meta-analyses (QUORUM) guidelines. Exercise effects were reported as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Six high-quality randomized controlled trials were included. For NSCLBP effects favored McKenzie therapy over intensive trunk strengthening for pain: SMD: short-term: 0.35 (0.10, 0.59); long-term 0.36 (0.12, 0.61) and short-term function: SMD: 0.45 (0.20, 0.70) and were comparable for medium-term function: SMD: 0.15 (-0.90, 0.40). Effects of favored McKenzie therapy were comparable to specific spinal stabilization exercises for short-term pain: SMD: 0.63 (-0.11, 1.38) and function: SMD: 0.47 (-0.27, 1.20). Pooled effects favored McKenzie therapy over other exercises for short-term pain (pooled SMD: 0.38 (0.14, 0.61)) and were comparable for short-term function: SMD: 0.10 (-0.20, 0.40). Yoga compared to trunk strengthening produced comparable effects for pain: (SMD: short-term: 0.13 (-0.46, 0.71); medium-term 0.51 (-0.08, 1.11)) and function SMD: short-term: 0.51 (-0.08, 1.10); medium-term 0.38 (-0.22, 0.97)). Compared to education, effects of yoga were large for medium-term pain and function (pooled SMDs: 0.92 (0.47, 1.37); 0.95 (0.50, 1.40)). Effects favored unloaded movement facilitation exercises of McKenzie compared to other or no exercise and were comparable for yoga. For NSCLBP, there is strong evidence that unloaded movement facilitation exercise, compared to no exercise, improves pain and function. Compared to other types of exercise, including effort-intensive strengthening and time-intensive stabilization exercise, the effects are comparable. This challenges the role of strengthening for NSCLBP.

  19. Management of hindlimb proximal suspensory desmopathy by neurectomy of the deep branch of the lateral plantar nerve and plantar fasciotomy: 155 horses (2003-2008). (United States)

    Dyson, S; Murray, R


    Neurectomy of the deep branch of the lateral plantar nerve and plantar fasciotomy have become accepted as methods of treatment of proximal suspensory desmopathy (PSD), but there are limited long-term studies documenting the outcome. To describe long-term follow-up in horses with PSD alone or with other injuries contributing to lameness and poor performance, including complications, following neurectomy and fasciotomy. Follow-up information was acquired for 155 horses that had undergone neurectomy and fasciotomy for treatment of PSD between 2003 and 2008. Success was classified as a horse having been in full work for >1 year post operatively. Horses were divided into 3 groups on the basis of the results of clinical assessment and diagnostic analgesia. Horses in Group 1 had primary PSD and no other musculoskeletal problem. Horses in Group 2 had primary PSD in association with straight hock conformation and/or hyperextension of the metatarsophalangeal joint. Horses in Group 3 had PSD and other problems contributing to lameness or poor performance. In Group 1, 70 of 90 horses (77.8%) had a successful outcome, whereas in Group 3, 23 of 52 horses (44.2%) returned to full function for >1 year. Complications included iatrogenic damage to the plantar aspect of the suspensory ligament, seroma formation, residual curb-like swellings and the development of white hairs. All horses in Group 2 remained lame. There is a role for neurectomy of the deep branch of the lateral plantar nerve and plantar fasciotomy for long-term management of hindlimb PSD, but a prerequisite for successful management requires recognition of risk factors for poor outcome including conformation features of straight hock or fetlock hyperextension. © 2011 EVJ Ltd.

  20. Granulocyte colony-stimulating factor (G-CSF protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats.

    Directory of Open Access Journals (Sweden)

    Ryo Kadota

    Full Text Available BACKGROUND: Granulocyte colony-stimulating factor (G-CSF is a protein that stimulates differentiation, proliferation, and survival of cells in the granulocytic lineage. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction and we previously reported the same effect in studies of murine spinal cord injury (SCI. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats. METHODS: Adult female Sprague-Dawley rats were used in the present study. Contusive SCI was introduced using the Infinite Horizon Impactor (magnitude: 200 kilodyne. Recombinant human G-CSF (15.0 µg/kg was administered by tail vein injection at 1 h after surgery and daily the next four days. The vehicle control rats received equal volumes of normal saline at the same time points. RESULTS: Using a contusive SCI model to examine the neuroprotective potential of G-CSF, we found that G-CSF suppressed the expression of pro-inflammatory cytokine (IL-1 beta and TNF- alpha in mRNA and protein levels. Histological assessment with luxol fast blue staining revealed that the area of white matter spared in the injured spinal cord was significantly larger in G-CSF-treated rats. Immunohistochemical analysis showed that G-CSF promoted up-regulation of anti-apoptotic protein Bcl-Xl on oligpodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. Moreover, administration of G-CSF promoted better functional recovery of hind limbs. CONCLUSIONS: G-CSF protects oligodendrocyte from SCI-induced cell death via the suppression of inflammatory cytokines and up-regulation of anti-apoptotic protein. As a result, G-CSF attenuates white matter loss and promotes hindlimb functional recovery.

  1. Endurance training induces fiber type-specific revascularization in hindlimb skeletal muscles of rats with chronic heart failure. (United States)

    Ranjbar, Kamal; Ardakanizade, Malihe; Nazem, Farzad


    Previous studies showed that skeletal muscle microcirculation was reduced in chronic heart failure. The aim of this study was to investigate the effects of endurance training on capillary and arteriolar density of fast and slow twitch muscles in rats with chronic heart failure. Four weeks after surgeries (left anterior descending (LAD) artery occlusion), chronic heart failure rats were divided into 3 groups: Sham (Sham, n=10); Sedentary (Sed, n=10); Exercise training (Ex, n=10). Ex group rats were subjected to endurance training in the form of treadmill running with moderate intensity for 10 weeks. Exercise training significantly increased capillary density and capillary to fiber ratio (Ptraining, but slow twitch muscle arteriolar density did not change in response to exercise in chronic heart failure rats. HIF-1 increased (Ptraining. In fast twitch muscle, HIF-1 mRNA increased (Ptraining. Endurance training ameliorates fast and slow twitch muscle revascularization non-uniformly in chronic heart failure rats by increasing capillary density in slow twitch muscle and arteriolar density in fast twitch muscle. The difference in revascularization at slow and fast twitch muscles may be induced by the difference in angiogenic and angiostatic gene expression response to endurance training.

  2. Centrally administered resistin enhances sympathetic nerve activity to the hindlimb but attenuates the activity to brown adipose tissue. (United States)

    Kosari, S; Rathner, J A; Chen, F; Kosari, S; Badoer, E


    Resistin, an adipokine, is believed to act in the brain to influence energy homeostasis. Plasma resistin levels are elevated in obesity and are associated with metabolic and cardiovascular disease. Increased muscle sympathetic nerve activity (SNA) is a characteristic of obesity, a risk factor for diabetes and cardiovascular disease. We hypothesized that resistin affects SNA, which contributes to metabolic and cardiovascular dysfunction. Here we investigated the effects of centrally administered resistin on SNA to muscle (lumbar) and brown adipose tissue (BAT), outputs that influence cardiovascular and energy homeostasis. Overnight-fasted rats were anesthetized, and resistin (7 μg) was administered into the lateral cerebral ventricle (intracerebroventricular). The lumbar sympathetic nerve trunk or sympathetic nerves supplying BAT were dissected free, and nerve activity was recorded. Arterial blood pressure, heart rate, body core temperature, and BAT temperature were also recorded. Responses to resistin or vehicle were monitored for 4 h after intracerebroventricular administration. Acutely administered resistin increased lumbar SNA but decreased BAT SNA. Mean arterial pressure and heart rate, however, were not significantly affected by resistin. BAT temperature was significantly reduced by resistin, and there was a concomitant fall in body temperature. The findings indicate that resistin has differential effects on SNA to tissues involved in metabolic and cardiovascular regulation. The decreased BAT SNA and the increased lumbar SNA elicited by resistin suggest that it may contribute to the increased muscle SNA and reduced energy expenditure observed in obesity and diabetes.

  3. Effects of an unloader knee brace on knee-related symptoms and function in people with post-traumatic knee osteoarthritis after anterior cruciate ligament reconstruction. (United States)

    Hart, Harvi F; Crossley, Kay M; Ackland, David C; Cowan, Sallie M; Collins, Natalie J


    This pilot study evaluated the immediate and four-week effects of an unloader knee brace on knee-related symptoms and performance-based function in people with knee osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR). Individuals with knee OA, five to 20years post-ACLR, were recruited for two within-subject randomized studies: immediate effects (n=18) and four-week effects (n=11). Patient-reported knee-related symptoms (knee pain, perceived task difficulty, confidence, stability) were assessed during hop for distance and step-down tests, while performance-based function was assessed with hopping distance under three conditions: i) no brace; ii) unadjusted brace (sagittal plane support); and iii) adjusted brace (sagittal plane support with varus/valgus readjustment). Participants in the four-week brace effect study were randomized to wear the unadjusted or adjusted brace for four weeks after baseline (no brace) testing, and repeated tests in their allocated brace at four-week follow-up. Friedman tests evaluated differences between the three brace conditions for each variable for the immediate brace effect study (pbrace and allocated brace for the four-week study (pbraces produced immediate improvements in knee confidence during hop for distance, and knee pain during step-down. Following the four-week brace intervention, the allocated brace improved knee confidence, perceived task difficulty and stability during hop for distance; and knee pain, perceived task difficulty, confidence, and stability during step-down. The unloader knee brace, adjusted or unadjusted, has the potential to improve knee-related symptoms associated with knee OA after ACLR. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Musculus gastrocnemius tetanus kinetics in alcohol-intoxicated rats with experimentally-induced hindlimb vascular ischemia under conditions of low-frequence muscle fatigue

    Directory of Open Access Journals (Sweden)

    O. A. Melnychuk


    Full Text Available Alcohol intoxication and ischemic injury of skeletal muscles often accompany each other. It is shown that patients hospitalized with chronic alcoholism develop muscle fatigue. Skeletal muscle dysfunction in alcohol-dependent patients is caused by ethanol-associated myofibrillar atrophy and metabolic disbalance, while compression-ischemic lesions result from unconsciousness of the patient, in case of taking the critical alcohol dose. Therefore, the aim of this study is to discover typical m. gastrocnemius (cap. med. tetanic kinetics changes in alcohol intoxicated rats with experimentally induced vascular ischemia of hindlimb muscles under conditions of low-frequency progressive muscle fatigue. Experiments were carried out on 10 young male Wistar rats (149.5 ± 5.8 g kept under standard vivarium conditions and diet. The investigation was conducted in two phases: chronic (30 days and acute (3 hours experiment. All surgical procedures were carried out aseptically under general anesthesia. Ishemic m. gastrocnemius (cap. med. tetanic kinetic changes and force productivity in alcohol intoxicated rats were investigated in the isometric mode, with direct electrical stimulation. The fatigue of m. gastrocnemius (cap. med. was evaluated by three characteristic criteria: the first sag effect, the secondary force rise, the second sag effect. There have been 10 similar experiments: 5 series in each study group with 10 tetanic runs in each series. The highest amplitude of the native m. gastrocnemius (cap. med. tetanus relative to isoline was taken as 100% force response. The same pattern of m. gastrocnemius (cap. med. low-frequency fatigue development was found in both rat groups under study. It is evidenced by the absence of substantial m. gastrocnemius (cap. med. tetanus kinetics differences in alcohol intoxicated rats, compared with non-alcohol intoxicated rats during fatigue test. However, the appreciable m. gastrocnemius (cap. med. tetanic force reduction

  5. Patellofemoral joint contact area increases with knee flexion and weight-bearing. (United States)

    Besier, Thor F; Draper, Christine E; Gold, Garry E; Beaupré, Gary S; Delp, Scott L


    Patellofemoral pain is a common and debilitating disorder. Elevated cartilage stress of the patellofemoral joint is hypothesized to play a role in the onset of pain. Estimating cartilage stress requires accurate measurements of contact area. The purpose of this study was to estimate patellofemoral joint contact areas in a group of healthy, pain-free subjects during upright, weight-bearing conditions. Sixteen subjects (8 female, 8 male) were scanned in a GE Signa SP open configuration MRI scanner, which allowed subjects to stand or squat while reclining 25 degrees from vertical with the knee positioned at 0 degrees , 30 degrees , or 60 degrees of flexion. A custom-built backrest enabled subjects to be scanned without motion artifact in both weight-bearing (0.45 body weight per leg) and reduced loading conditions ('unloaded' at 0.15 body weight) at each knee flexion posture. Male subjects displayed mean unloaded patellofemoral joint contact areas of 210, 414, and 520 mm(2) at 0 degrees , 30 degrees and 60 degrees of knee flexion, respectively. Female subjects' unloaded contact areas were similar at full extension (0 degrees ), but significantly smaller at 30 degrees and 60 degrees (pweight-bearing conditions, contact areas increased by an average of 24% (pknee flexion postures, and physiologic loading conditions.

  6. Inhibition of xanthine oxidase by allopurinol prevents skeletal muscle atrophy: role of p38 MAPKinase and E3 ubiquitin ligases.

    Directory of Open Access Journals (Sweden)

    Frederic Derbre

    Full Text Available Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO. The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in rats, and its possible prevention by allopurinol, a well-known inhibitor of this enzyme. For this purpose we studied one of the main redox sensitive signalling cascades involved in skeletal muscle atrophy i.e. p38 MAPKinase, and the expression of two well known muscle specific E3 ubiquitin ligases involved in proteolysis, the Muscle atrophy F-Box (MAFbx; also known as atrogin-1 and Muscle RING (Really Interesting New Gene Finger-1 (MuRF-1. We found that hindlimb unloading induced a significant increase in XO activity and in the protein expression of the antioxidant enzymes CuZnSOD and Catalase in skeletal muscle. The most relevant new fact reported in this paper is that inhibition of XO with allopurinol, a drug widely used in clinical practice, prevents soleus muscle atrophy by ~20% after hindlimb unloading. This was associated with the inhibition of the p38 MAPK-MAFbx pathway. Our data suggest that XO was involved in the loss of muscle mass via the activation of the p38MAPK-MAFbx pathway in unloaded muscle atrophy. Thus, allopurinol may have clinical benefits to combat skeletal muscle atrophy in bedridden, astronauts, sarcopenic, and cachexic patients.

  7. Design and construction of coal unloading bridge at Hekinan thermal power plant. Hekinan karyoku hatsudensho yotan sanbashi no sekkei to seko

    Energy Technology Data Exchange (ETDEWEB)

    Kanetani, Y.; Tamaki, K.; Nishio, Y. (Chubu Electric Power Co. Inc., Nagoya, (Japan))


    A coal firing power plant (700,000kW {times} 3) is under construction at Hekinan City in Aichi Prefecture, Japan. A report is made on the design and construction work of the coal unloading bridge which is nearly completed. About 4.65 million tons of coal/year is expected to be landed mostly from ocean-going ships, but the bridge is so designed as to serve as a combination berth for ocean-going ships and coastwise vessels because a small quantity of coal is landed from coasting vessels as well. Outlines of the scale and layout of the landing bridge, anchorage, and facilities on the bridge are introduced. In connection with the design conditions, conditions of ship, meteorological and hydrographic conditions, submarine geography, geological conditions, design seismic intensity, design load, etc. are explained. As to the outline of structure, description is made on the selection of structural type, determination of optimum block length, height of the bridge top, structural analysis, outline of structure and corrosion resistance. As regards the outline of the work, number of works, work flow, result of processes, rapid construction, and the arrangement of heavy machines are described. Subjects concerning pile driving work and superstructure work are also reported. 13 figs., 10 tabs.


    Directory of Open Access Journals (Sweden)

    V. A. Bratash


    Full Text Available In the article the calculation formulas for determination of unloadings (finishings loadings of wheels and bendings of a spring suspension of 8-wheel electric locomotive DS 3 with the hauling transmission of the second kind at the transmission of tractive forces from the bogies to the body through sloping tractions are presented. Numerical calculations are executed on the example of mainline freight-and-passenger electric locomotive DS 3.

  9. Feature articles, thermal power and atomic power. Design and construction of the cargo unloading jetty of Misumi power station. Karyoku, genshiryoku. Misumi hatsudensho butsuyo sanbashi no sekkei/seko ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, I.; Ishimoto, M.; Ichinose, Y. (Chugoku Electric Power Co. Inc., Hiroshima (Japan))


    The Chugoku Electric Power Co., Ltd. is now constructing a cargo unloading jetty for bringing in materials and machines for the construction of the power station together with the coal unloading quay and the oil unloading quay at the east berth of the power station, as a part of the land reclamation work for Misumi power station in Shimane Prefecture. In this article, the design and construction of this jetty are to make the normal lines of these quays and the jetty aligned straight in order to allow a ship to lay alongside the two adjoining piers across their boundary, and to make its revetment portion with a water intake recede in the concave manner and adopt the flat slab structure supported with steel pipe piles to this portion in order to let this jetty function also as the deep water intaking facility for the condenser cooling water. Since the uplift pressure of the incident waves work on the slabs structurally, this effect has been reflected in the design after conducting an experiment using a hydromodel. Concerning steel pipe piles, driving of these piles into the bottom rock bed with the uniaxial compression pressure of 1,500kgf/cm[sup 2] in maximum has been conducted. On the front face of the above jetty, a curtain wall has been installed for intaking the deep water. It planned to complete the construction work in the end of 1994. 7 refs., 19 figs., 7 tabs.

  10. Rapid ice unloading in the Fleming Glacier region, southern Antarctic Peninsula, and its effect on bedrock uplift rates

    DEFF Research Database (Denmark)

    Zhao, Chen; King, Matt A.; Watson, Christopher S.


    m at the front of Fleming Glacier. Using IceBridge and ICESat-2/GLAS data spanning 2002–2014, we show an increased rate of mean ice-surface lowering, with rates post-2008 more than twice those of 2002–2008. We use these load change data as a basis for the simulation of viscoelastic solid Earth...... deformation. We subtract modeled elastic deformation rates, and a suite of modeled viscous rates, from GPS-derived three-dimensional bedrock velocities at sites to the south of Fleming Glacier to infer properties of Earth rheology. Assuming the pre-breakup bedrock uplift was positive due to post-Last Glacial...... the Fleming Glacier, after the application of elastic and plate tectonic corrections, point away from Marguerite Bay rather than the present glacier front. This suggests that horizontal motion in the region reflects the earlier retreat of the glacier system following the LGM, compatible with a relatively...

  11. Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading (United States)

    Kubota, Takuo; Elalieh, Hashem Z.; Saless, Neema; Fong, Chak; Wang, Yongmei; Babey, Muriel; Cheng, Zhiqiang; Bikle, Daniel D.


    Skeletal loading and unloading has a pronounced impact on bone remodeling, a process also regulated by insulin-like growth factor-1 (IGF-1) signaling. Skeletal unloading leads to resistance to the anabolic effect of IGF-1, while reloading after unloading restores responsiveness to IGF-1. However, a direct study of the importance of IGF-1 signaling in the skeletal response to mechanical loading remains to be tested. In this study, we assessed the skeletal response of osteoblast-specific Igf-1 receptor deficient (Igf-1r-/-) mice to unloading and reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16 days. Igf-1r-/- mice displayed smaller cortical bone and diminished periosteal and endosteal bone formation at baseline. Periosteal and endosteal bone formation decreased with unloading in Igf-1r+/+ mice. However, the recovery of periosteal bone formation with reloading was completely inhibited in Igf-1r-/- mice, although reloading-induced endosteal bone formation was not hampered. These changes in bone formation resulted in the abolishment of the expected increase in total cross-sectional area with reloading in Igf-1r-/- mice compared to the control mice. These results suggest that the Igf-1r in mature osteoblasts has a critical role in periosteal bone formation in the skeletal response to mechanical loading.

  12. The Effects of Using a Ramp and Elevator to Load and Unload Trailers on the Behavior and Physiology of Piglets

    Directory of Open Access Journals (Sweden)

    John McGlone


    Full Text Available Transport is an inevitable process in the modern U.S. swine industry. The loading process is a novel and potentially stressful experience. This study uses behavior, heart rate and leukocyte counts to compare stress one hour before, during and after loading via ramp or elevator. Piglets were held in a home pen (control (CON, walked up and down an aisle (handled (HAN, or walked to a truck and loaded via elevator (ELE or ramp (RAM. Sitting, feeding and blood parameters did not show a significant treatment by time effect (p > 0.05. Standing behavior did not differ between CON and HAN piglets nor between RAM and ELE piglets (p > 0.05; however, CON and HAN piglets stood more than RAM and ELE piglets during treatment (p < 0.05. After treatment, drinking behavior was increased in RAM piglets (p < 0.05. The heart rate of ELE piglets decreased 6.3% after treatment; whereas the heart rate of RAM piglets remained elevated 2.4% (p < 0.05. In terms of heart rate, loading by elevator appears to be less stressful than loading by ramp.

  13. Hindlimb Suspension (HLS) in Rodents for the Study of Intracranial Pressure, Molecular and Histologic Changes in the Eye, and CSF Production Regulation and Resorption: A Status Report of Two Studies (United States)

    Theriot, C. A.; Taibbi, G.; Vizzeri, G.; Parsons-Wingerter, P.; Chevez-Barrios, P.; Rivera, A.; Zanello, S. B.


    This status report corresponds to two studies tied to an animal experiment being executed at the University of California Davis (Charles Fuller's laboratory). The animal protocol uses the well-documented rat hindlimb suspension (HLS) model, to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. Long Evans rats are subjected to HLS durations of 7, 14, 28 and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28 or 90 days. All HLS subjects have age-matched cage controls. Various animal cohorts are planned for this study: young males, young females and old males. In addition to the live measures (ICP by telemetry, IOP and retinal parameters by optical coherence tomography) which are shared with the Fuller study, the specific outcomes for this study include: -Gene expression analysis of the retina -Histologic analysis - Analysis of the microvasculature of retina flat mounts by NASA's VESsel GENeration Analysis (VESGEN) Software. To date, the young male and female cohorts are being completed. Due to the need to keep technical variation to a minimum, the histologic and genomic analyses have been delayed until all samples from each cohort are available and can be processed in a single batch per cohort. The samples received so far correspond to young males sacrificed at 7,14, 28 and 90 days of HLS and at 90 days of recovery; and from young females sacrificed at 7, 14 and 28 of HLS. A complementary study titled: "A gene expression and histologic approach to the study of cerebrospinal fluid (CSF) production and outflow in hindlimb suspended rats" seeks to study the molecular components of CSF production and outflow modulation as a result of HLS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid villi and choroid plexus of HLS rats compared to rats in normal

  14. Rapid ice unloading in the Fleming Glacier region, southern Antarctic Peninsula, and its effect on bedrock uplift rates (United States)

    Zhao, Chen; King, Matt A.; Watson, Christopher S.; Barletta, Valentina R.; Bordoni, Andrea; Dell, Matthew; Whitehouse, Pippa L.


    Rapid regional warming in the Antarctic Peninsula has led to the significant retreat and eventual collapse of several major ice shelves since the 1970s, triggering the subsequent acceleration and thinning of their feeding glaciers. The Wordie Ice Shelf, lying off the west coast of the Antarctic Peninsula, has undergone long-term disintegration since the 1960s with a substantial calving event occurring around 1989, followed by continuous steady retreat and its almost-complete disappearance. The dynamic response of the upstream glaciers to the ice shelf collapse and the response of the solid Earth to the associated mass loss are not fully understood. To quantify the mass loss from the system, we generated a digital elevation model (DEM) using airborne vertical and oblique imagery from 1966 and compared it to a DEM derived from 2008 SPOT data. This analysis reveals lowering over that time of approximately 60 m at the front of Fleming Glacier. Using IceBridge and ICESat-2/GLAS data spanning 2002-2014, we show an increased rate of mean ice-surface lowering, with rates post-2008 more than twice those of 2002-2008. We use these load change data as a basis for the simulation of viscoelastic solid Earth deformation. We subtract modeled elastic deformation rates, and a suite of modeled viscous rates, from GPS-derived three-dimensional bedrock velocities at sites to the south of Fleming Glacier to infer properties of Earth rheology. Assuming the pre-breakup bedrock uplift was positive due to post-Last Glacial Maximum (LGM) ice retreat, our viscoelastic-corrected GPS uplift rates suggest upper mantle viscosities are > 2 ×1019 Pas and likely > 1 ×1020 Pas in this region, 1-2 orders of magnitude greater than previously found for the northern Antarctic Peninsula. Horizontal velocities at the GPS site nearest the Fleming Glacier, after the application of elastic and plate tectonic corrections, point away from Marguerite Bay rather than the present glacier front. This suggests

  15. Price increase

    CERN Multimedia


    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  16. Price increase

    CERN Multimedia


    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced, as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  17. Pharmacokinetics of Acetaminophen in Hind Limbs Unloaded Mice: A Model System Simulating the Effects of Low Gravity on Astronauts in Space (United States)

    Peterson, Amanda; Risin, Semyon A.; Ramesh, Govindarajan T.; Dasgupta, Amitava; Risin, Diana


    The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in Space. Low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration in astronauts. Acquiring of such knowledge has inherent difficulties due to limited opportunities for experimenting in Space. One of the approaches is to use model systems that simulate some of the Space conditions on Earth. In this study we used hind limbs unloaded mice (HLU) to investigate the possible changes in PK of acetaminophen, a widely used analgesic with high probability of use by astronauts. The HLU is recognized as an appropriate model for simulating the effects of low gravity on hemodynamic parameters. Mice were tail suspended (n = 24) for 24-96 hours prior to introduction of acetaminophen (150 - 300 mg/kg). The drug (in aqueous solution containing 10% ethyl alcohol by volume) was given orally by a gavage procedure and after the administration of acetaminophen mice were additionally suspended for 30 min, 1 and 2 hours. Control mice (n = 24) received the same dose of acetaminophen and were kept freely all the time. Blood specimens were obtained either from retroorbital venous sinuses or from heart. Acetaminophen concentration was measured in plasma by the fluorescent polarization immunoassay and the AxSYM analyzer (Abbott Laboratories). In control mice peak acetaminophen concentration was achieved at 30 min. By 1 hour the concentration decreased to less than 50% of the peak level and at 2 hours the drug was almost undetectable in the serum. HLU for 24 hours significantly altered the acetaminophen pharmacokinetic: at 30 min the acetaminophen concentrations were significantly (both statistically and medically significant) lower than in control mice. The concentrations also reduced less

  18. Transversal Stiffness and Beta-Actin and Alpha-Actinin-4 Content of the M. Soleus Fibers in the Conditions of a 3-Day Reloading after 14-Day Gravitational Unloading

    Directory of Open Access Journals (Sweden)

    I. V. Ogneva


    Full Text Available The aim of the work was to analyze the structural changes in different parts of the sarcolemma and contractile apparatus of muscle fibers by measuring their transversal stiffness by atomic force microscopy in a three-day reloading after a 14-day gravity disuse, which was carried out by hind-limbs suspension. The object of the study was the soleus muscle of the Wistar rat. It was shown that after 14 days of disuse, there was a reduction of transversal stiffness of all points of the sarcolemma and contractile apparatus. Readaptation for 3 days leads to complete recovery of the values of the transversal stiffness of the sarcolemma and to partial value recovery of the contractile apparatus. The changes in transversal stiffness of sarcolemma correlate with beta-actin and alpha-actinin-4 in membrane protein fractions.

  19. Increased magma production and volcanism triggered by the Messinian Salinity Crisis (United States)

    Sternai, Pietro; Caricchi, Luca; Garcia-Castellanos, Daniel; Castelltort, Sebastien


    For more than four decades, large controversies about the causes, effects and timing of the Mediterranean Messinian Salinity Crisis (MSC) have evolved in the light of a continuously growing body of evidences. The igneous response to such extreme event, however, has remained largely unexplored despite known relationships between surface load variations and the production of magma. Here, we compile published geochemical and isotopic data and recognize a two-fold increase of volcanic eruptions from pan-Mediterranean magmatic provinces coinciding with the proposed "shallow-water phase" of the MSC between 5.70-5.33 Ma. Estimates of surface load variations due to the desiccation event corrected for water density change and deposition of salt deposits suggest a net mean lithospheric unloading of up to 15 MPa during the shallow-water phase of the MSC. Because the timescale of interest is too short for changes of the Mediterranean tectonics to significantly affect the bulk of the magma production, we propose that such net surface unloading enhanced the mantle decompression melting and dike formation, in turn causing the observed increase of volcanic events. If correct, the Mediterranean magmatic record provides an independent validation of the "shallow-water" model for the formation of salt deposits and testifies the high sensitivity of the melting of the Earth's interior to the surface forcing.

  20. Unilateral hindlimb casting induced a delayed generalized muscle atrophy during rehabilitation that is prevented by a whey or a high protein diet but not a free leucine-enriched diet.

    Directory of Open Access Journals (Sweden)

    Hugues Magne

    Full Text Available Sarcopenia is the general muscle mass and strength loss associated with ageing. Muscle atrophy could be made worse by exposure to acute periods of immobilization, because muscle disuse by itself is a stimulus for atrophy. Using a model of unilateral hindlimb casting in old adult rats, we have already demonstrated that the primary effect of immobilization was atrophy in the casted leg, but was also surprisingly associated with a retarded atrophy in the non-casted leg during rehabilitation. In search of mechanisms involved in this generalized atrophy, we demonstrated in the present study that contrary to pair-fed non-immobilized control animals, muscle protein synthesis in the non-immobilized limb was unable to adapt and to respond positively to food intake. Because pair-fed control rats did not lose muscle mass, this defect in muscle protein synthesis may represent one of the explanation for the muscle mass loss observed in the non-immobilized rats. Nevertheless, in order to stimulate protein turn over and generate a positive nitrogen balance required to maintain the whole muscle mass in immobilized rats, we tested a dietary free leucine supplementation (an amino acid known for its stimulatory effect on protein metabolism during the rehabilitation period. Leucine supplementation was able to overcome the anabolic resistance in the non-immobilized limb. A greater muscle protein synthesis up-regulation associated with a stimulation of the mTOR signalling pathway was indeed recorded but it remained inefficient to prevent the loss of muscle in the non-immobilized limb. By contrast, we demonstrated here that whey protein or high protein diets were able to prevent the muscle mass loss of the non-immobilized limb by sustaining muscle protein synthesis during the entire rehabilitation period.

  1. MAb therapy against the IFN-α/β receptor subunit 1 stimulates arteriogenesis in a murine hindlimb ischaemia model without enhancing atherosclerotic burden

    NARCIS (Netherlands)

    Teunissen, Paul F. A.; Boshuizen, Marieke C.; Hollander, Maurits R.; Biesbroek, Paul S.; van der Hoeven, Nina W.; Mol, Jan-Quinten; Gijbels, Marion J.; van der Velden, Saskia; van der Pouw Kraan, Tineke C.; Horrevoets, Anton J.; de Winther, Menno P.; van Royen, Niels


    IFN-beta (IFNβ) signalling is increased in patients with insufficient coronary collateral growth (i.e. arteriogenesis) and IFNβ hampers arteriogenesis in mice. A downside of most pro-arteriogenic agents investigated in the past has been their pro-atherosclerotic properties, rendering them unsuitable

  2. Mature IGF-I excels in promoting functional muscle recovery from disuse atrophy compared with pro-IGF-IA (United States)

    Park, SooHyun; Brisson, Becky K.; Liu, Min; Spinazzola, Janelle M.


    Prolonged disuse of skeletal muscle results in atrophy, and once physical activity is resumed, there is increased susceptibility to injury. Insulin-like growth factor-I (IGF-I) is considered a potential therapeutic target to attenuate atrophy during unloading and to enhance rehabilitation upon reloading of skeletal muscles, due to its multipronged actions on satellite cell proliferation, differentiation, and survival, as well as its actions on muscle fibers to boost protein synthesis and inhibit protein degradation. However, the form of IGF-I delivered may alter the success of treatment. Using the hindlimb suspension model of disuse atrophy, we compared the efficacy of two IGF-I forms in protection against atrophy and enhancement of recovery: mature IGF-I (IGF-IS) lacking the COOH-terminal extension, called the E-peptide, and IGF-IA, which is the predominant form retaining the E-peptide. Self-complementary adeno-associated virus harboring the murine Igf1 cDNA constructs were delivered to hindlimbs of adult female C57BL6 mice 3 days prior to hindlimb suspension. Hindlimb muscles were unloaded for 7 days and then reloaded for 3, 7, and 14 days. Loss of muscle mass following suspension was not prevented by either IGF-I construct. However, IGF-IS expression maintained soleus muscle force production. Further, IGF-IS treatment caused rapid recovery of muscle fiber morphology during reloading and maintained muscle strength. Analysis of gene expression revealed that IGF-IS expression accelerated the downregulation of atrophy-related genes compared with untreated or IGF-IA-treated samples. We conclude that mature-IGF-I may be a better option than pro-IGF-IA to promote skeletal muscle recovery following disuse atrophy. PMID:24371018

  3. Effect of selective blockade of M4 cholinoreceptors by tropicamide on blood supply in brain, splanchnic azygous organs, and hindlimbs in intact rats. (United States)

    Kovalenko, N Ya; Matsievskii, D D; Reshetnyak, V K


    Experiments on anesthetized rats carried out with a high-frequency ultrasonic system and tropicamide, a highly selective blocker of M4 cholinoreceptors, showed that the vasodilator effects observed after selective blockade of M4 cholinoreceptors are not organ-specific. Intravenous tropicamide (0.1 μg/kg body weight) transiently decreased systemic BP, elevated the linear and volume fl ow rates, and diminished vascular resistance in common carotid, superior mesenteric, and femoral arteries. At the same time, in most rats (76%) the fl ow rate in the portal vein did not change, while in 25% rats it insignificantly and temporarily increased. The hypothesis on possible involvement of M4 cholinoreceptor structures in cholinergic vasoconstriction is discussed.

  4. Shock wave treatment induces angiogenesis and mobilizes endogenous CD31/CD34-positive endothelial cells in a hindlimb ischemia model: implications for angiogenesis and vasculogenesis. (United States)

    Tepeköylü, Can; Wang, Feng-Sheng; Kozaryn, Radoslaw; Albrecht-Schgoer, Karin; Theurl, Markus; Schaden, Wolfgang; Ke, Huei-Jin; Yang, Yaju; Kirchmair, Rudolf; Grimm, Michael; Wang, Ching-Jen; Holfeld, Johannes


    Shock waves have been shown to induce recruitment of intravenously injected endothelial progenitor cells to ischemic hind limbs in rats. We hypothesized that shock wave treatment as sole therapy would induce angiogenesis in this ischemia model and would lead to mobilization of endogenous endothelial (progenitor) cells. A total of 18 rats, aged 5 weeks old, were subdivided into 3 groups: sham (n = 6), ischemic muscle with shock wave treatment (shock wave treatment group, n = 6), and without shock wave treatment (control, n = 6). Hind limb ischemia was induced by ligation of the femoral artery. Three weeks later, shock wave treatment (300 impulses at 0.1 mJ/mm(2)) was applied to the adductor muscle; the controls were left untreated. Muscle samples were analyzed using real-time polymerase chain reaction for angiogenic factors and chemoattractants for endothelial progenitor cell mobilization. Fluorescence activated cell sorting analysis of the peripheral blood was performed for CD31/CD34-positive cells. Perfusion was measured using laser Doppler imaging. Functional improvement was evaluated by walking analysis. Angiogenic factors/endothelial progenitor cell chemoattractants, stromal cell-derived factor-1 and vascular endothelial growth factor, were increased in the treatment group, as shown by real-time polymerase chain reaction, indicating the mobilization of endothelial progenitor cells. Fluorescence activated cell sorting analysis of the peripheral blood revealed high numbers of CD31/CD34-positive cells in the treatment group. Greater numbers of capillaries were found in the treated muscles. Blood perfusion increased markedly in the treatment group and led to functional restoration, as shown by the results from the walking analysis. Shock wave therapy therefore could develop into a feasible alternative to stem cell therapy in regenerative medicine, in particular for ischemic heart and limb disease. Copyright © 2013 The American Association for Thoracic

  5. Intermittent application of hypergravity by centrifugation attenuates disruption of rat gait induced by 2 weeks of simulated microgravity. (United States)

    Tajino, Junichi; Ito, Akira; Nagai, Momoko; Zhang, Xiangkai; Yamaguchi, Shoki; Iijima, Hirotaka; Aoyama, Tomoki; Kuroki, Hiroshi


    The effects of intermittent hypergravity on gait alterations and hindlimb muscle atrophy in rats induced by 2 weeks of simulated microgravity were investigated. Rats were submitted to hindlimb unloading for 2 weeks (unloading period), followed by 2 weeks of reloading (recovery period). During the unloading period, animals were subjected to the following treatments: (1) free in cages (Control); (2) continuous unloading (UL); (3) released from unloading for 1 hour per day (UL+1G); (4) hypergravity for 1h per day using a centrifuge for small animals (UL+2G). The relative weights of muscles to the whole body weight and kinematics properties of hindlimbs during gait were evaluated. UL rats walked with their hindlimbs overextended, and the oscillation of their limb motion had become narrowed and forward-shifted after the unloading period, and this persisted for at least 2 weeks after the termination of unloading. However, these locomotor alterations were attenuated in rats subjected to UL+2G centrifugation despite minor systematic changes in muscle recovery. These findings indicate hypergravity application could counteract the adverse effects of simulated or actual microgravity environments. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Effects of primary and recurrent sacral chordoma on the motor and nociceptive function of hindlimbs in rats: an orthotopic spine model. (United States)

    Sarabia-Estrada, Rachel; Ruiz-Valls, Alejandro; Shah, Sagar R; Ahmed, A Karim; Ordonez, Alvaro A; Rodriguez, Fausto J; Guerrero-Cazares, Hugo; Jimenez-Estrada, Ismael; Velarde, Esteban; Tyler, Betty; Li, Yuxin; Phillips, Neil A; Goodwin, C Rory; Petteys, Rory J; Jain, Sanjay K; Gallia, Gary L; Gokaslan, Ziya L; Quinones-Hinojosa, Alfredo; Sciubba, Daniel M


    OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test

  7. Fatigue test of a fiberglass based composite panel. Increasing the lifetime of freight wagon (United States)

    Sobek, M.; Baier, A.; Grabowski, Ł.; Majzner, M.


    In the XXI century transportation of goods plays a key role in the economy. Due to a good logistics the economy is able to grow fluently. Although land transportation is carried out mainly through trucks for the last several years there has been noted an increase in the percentage share of rail transport in the freight transport. The main goods transported by railways are mineral fuels, mining and quarrying products. They constitute the greater part of 70% of total transported goods. Transportation of material of such high weight, high hardness and with different shapes involves increased and accelerated wear and tear of the cargo space of the wagon. This process is also magnified by substances used to prevent overheating or goods theft. Usually they are in the form of chemical compounds powder, eg. Calcium. A very large impact on the wear of the freight wagons hull is made because of mechanical damage. Their source comes mostly from loading cargo with impetus and using heavy machines during unloading. A large number of cycles of loading and unloading during the working period causes abrasion of body and as a result after several years a wagon car qualifies for a major maintenance. Possibility of application composite panels in the process of renovating the wagons body could reduce the weight of whole train and prolong the service life between mandatory technical inspection. The Paper "Fatigue test of a fiberglass based composite panel. Increasing the lifetime of freight wagon" presents the research process and the results of the endurance test of the composite panel samples fixed to a metal plate. As a fixing method a stainless steel rivet nut and a stainless steel button head socket screws were chosen. Cyclic and multiple load were applied to test samples using a pneumatic cylinder. Such a methodology simulated the forces resulting from loading and unloading of the wagon and movement of the cargo during transport. In the study a dedicated stand equipped with a

  8. Load and unload system optimization on H{sub 2} {sup 18} O irradiation target used for {sup 18}F{sup -} production at the cyclotron cyclone 30 from IPEN-CNEN/SP, Brazil; Otimizacao do sistema de carga e descarga no porta-alvo de irradiacao de H{sub 2} {sup 18} O utilizado para a producao de {sup 18}F{sup -} no ciclotron cyclone 30 do IPEN-CNEN/SP

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Osvaldo Luiz da


    The demand growing in Brazil by the radiopharmaceutical [{sup 18}F] FDG in positron emission tomography (PET-CT) and the 109,7 minutes half life claim special attention to the productive chain of this radiopharmaceutical. Since the [{sup 18}O]water irradiation until the tomograph patient scanning, in sequential procedures that may spent about six hours, all the productive chain stages must be as reliable as possible, because any stage failed will be perceived in productive chain extremity. The position indication absence from Load and Unload {sup 18}F{sup -} Target System valve in Cyclotron Accelerators Center resulted in {sup 18}F{sup -} production loss, Irradiation Room contamination and the increase workers dose responsible by operation and maintenance of irradiation systems. This study tested the behaviour of three types of position sensors (micro switch, reed switch and inductive sensor), into Irradiation Room 1.2 environment of the Cyclotron Accelerators Center, where there are high gamma radiation and neutrons rates because the routine {sup 18}F{sup -} and {sup 123}I production, through this test was possible to discover the fitter position sensor to run on {sup 18}F{sup -} Target, and after rewriting the programmable logic controller software was possible avoid this type of fail at {sup 18}F{sup -} production time in Cyclotron Accelerators Center, and to grow up the reliability on [{sup 18}F]FDG productive chain. (author)

  9. Load unload system optimization on H{sub 2}{sup 18}O irradiation target used for {sup 18}F{sup -} production at the cyclotron cyclone 30 from IPEN-CNEN/SP; Otimizacao do sistema carga e descarga no portal-alvo de irradiacao de H{sub 2}{sup 18}O utilizado para a producao de {sup 18}F{sup -} no ciclotron cyclone 30 do IPEN-CNEN/SP

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Osvaldo Luiz da


    The demand growing in Brazil by the radiopharmaceutical [{sup 18}F]FDG in positron emission tomography (PET-CT) and the 109,7 minutes half life claim special attention to the productive chain of this radiopharmaceutical. Since the [{sup 18}O]water irradiation until the tomograph patient scanning, in sequential procedures that may spent about six hours, all the productive chain stages must be as reliable as possible, because any stage failed will be perceived in productive chain extremity. The position indication absence from Load and Unload {sup 18}F- Target System valve in Cyclotron Accelerators Center resulted in {sup 18}F- production loss, Irradiation Room contamination and the increase workers' dose responsible by operation and maintenance of irradiation systems. This study tested the behaviour of three types of position sensors (micro switch, reed switch and inductive sensor), into Irradiation Room 1.2 environment of the Cyclotron Accelerators Center, where there are high gamma radiation and neutrons rates because the routine {sup 18}F- and {sup 1}'2{sup 3}I production, through this test was possible to discover the fitter position sensor to run on {sup 18}F- Target, and after rewriting the programmable logic controller software was possible avoid this type of fail at {sup 18}F- production time in Cyclotron Accelerators Center, and to grow up the reliability on [{sup 18}F]FDG productive chain. (author)

  10. Loaded versus unloaded magnetic resonance imaging (MRI of the knee: Effect on meniscus extrusion in healthy volunteers and patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Rina Patel


    Conclusion: Our study demonstrated that medial meniscal extrusion significantly increased during loading, specifically in those low KL scores (0 and 1 and in KL score of 3. Loaded MRI may more accurately determine the extent of medial meniscal extrusion in particular in those with no to minimal OA.

  11. Using the ratio: maximum load over unload stiffness squared, Pm/Su², on the evaluation of machine stiffness and area function of blunt indenters on depth-sensing indentation equipment

    Directory of Open Access Journals (Sweden)

    Juan Manuel Meza


    Full Text Available Depth sensing indentation study was conducted in a Fischerscope H100V machine, equipped with a Vickers indenter with a tip roundness of approximately 1330 nm. Tests were carried out on soda-lime glass, fused silica, sapphire, aluminum (1100 alloy, high alloyed steel, titanium and copper. The widely used iterative method of Oliver and Pharr was unsuccessful in the attempts to analyze machine compliance and indenter area function. Therefore, an alternative procedure was adopted. The alternative procedure is based on the ratio between maximum load and unload stiffness squared, Pm/Su². It was found that this procedure, which is not iterative, gives good results. A careful study of the Pm/Su² ratio, lead us to conclude that the Fischercope machine has a low compliance which depends on the sample mounting. This low compliance in conjunction with the recent discovery of the dependence of beta factor on the tip roundness/maximum depth ratio, which appears in the relation between contact stiffness and contact area, explains why the iterative method does not converge. However, variations in beta and machine compliance produces deviation on the hardness and elastic modulus lower that 6% with respect to expected values for the materials and the machine studied in this work.

  12. [Insulin-like growth factor 1 and the key markers of proteolysis during the acute period of readaptation of the muscle atrophied as a result of unloading]. (United States)

    Kachaeva, E V; Turtikova, O V; Leĭnsoo, T A; Shenkman, B S


    It has been shown that, after prolonged disuse, the accumulation of muscle mass and the recovery of soleus fibers volume are caused by water accumulation rather than protein synthesis intensification. At the same time, expression rate of the main markers of the activity of ubiquitin-proteasome system remained increased on the 3rd day of reloading and decreased to the control by the 7th day. Both the quantity of the insulin-like growth factor 1 and the number of satellite cells fused with muscle fibers and of myonuclei began to increase only on the 7th day of reloading. The data obtained evidenced a significant inertness of the postural muscle during its adaptation to the load (normal gravity) after prolonged disuse.

  13. The Late Miocene to recent erosion pattern of the Alpine foreland basin reflects Eurasian slab-unloading beneath the western Alps rather than global climate change (United States)

    Friedrich, Anke; Schlunegger, Fritz; Baran, Ramona


    It has been proposed that mountainous erosion increased globally around 5 Ma in response to global climate change, mainly because this increase coincides with a cooling trend indicated by global isotopic data (e.g., Herman et al. 2013). The Alps have played a prominent role in this debate. Published sedimentary budgets for the western and eastern Alps for the past 35 Ma show a substantial increase in the erosion of the Alps at c. 5 Ma (e.g., Kuhlemann, 2000). This temporal coincidence was used to call for a climate driver, mainly because this increase was not accompanied by tectonic convergence across the Alps during this time period. However, several authors emphasized the importance of lithospheric-scale processes beneath the Alps, which could also explain the increase in erosion rates through surface uplift. To provide a new perspective on this debate, we synthesized a spatial gradient map of erosion rates for the Alps and the entire Alpine foreland basin. Our data base consists of published (1) apatite fission-track (AFT) cooling ages for the Alps (e.g., Vernon et al. 2008; Luth and Willingshofer 2008; Wölfler et al. 2012; (2) AFT ages from wells from the Swiss foreland basin (e.g., Cederbom et al. 2011), and (3) stratigraphic data from industry wells in the German and Austrian foreland basin (e.g., Lemcke 1974; Genser et al. 2007). We focus our analysis on the shape and scale of the areas undergoing erosion since 5 Ma. Our synthesis of published denudation rate data for the past 5 Million years reveals that erosion of the Alpine foreland basin is highest in front of the western Alps (between 2 and 0.6 km), and decreases eastward over a distance of 700 km to the Austrian foreland basin (c. 200 m). For the western Alps, the compilation of apatite-fission-track ages yields erosion rates > 0.6 km/Ma, while erosion rates for the eastern foreland basin and the adjacent eastern Alps are slab along the Eurasian-Adriatic plate boundary. This mechanism triggered large

  14. Monosodium iodoacetate-induced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Jarvis Michael F


    Full Text Available Abstract Background Intra-articular injection of monosodium iodoacetate (MIA in the knee joint of rats disrupts chondrocyte metabolism resulting in cartilage degeneration and subsequent nociceptive behavior that has been described as a model of osteoarthritis (OA pain. Central sensitization through activation of mitogen activated protein kinases (MAPKs is recognized as a pathogenic mechanism in chronic pain. In the present studies, induction of central sensitization as indicated by spinal dorsal horn MAPK activation, specifically ERK and p38 phosphorylation, was assessed in the MIA-OA model. Results Behaviorally, MIA-injected rats displayed reduced hind limb grip force 1, 2, and 3 weeks post-MIA treatment. In the same animals, activation of phospho ERK1/2 was gradually increased, reaching a significant level at post injection week 3. Conversely, phosphorylation of p38 MAPK was enhanced maximally at post injection week 1 and decreased, but remained elevated, thereafter. Double labeling from 3-wk MIA rats demonstrated spinal pERK1/2 expression in neurons, but not glia. In contrast, p-p38 was expressed by microglia and a subpopulation of neurons, but not astrocytes. Additionally, there was increased ipsilateral expression of microglia, but not astrocytes, in 3-wk MIA-OA rats. Consistent with increased MAPK immunoreactivity in the contralateral dorsal horn, mechanical allodynia to the contralateral hind-limb was observed 3-wk following MIA. Finally, intrathecal injection of the MEK1 inhibitor PD98059 blocked both reduced hind-limb grip force and pERK1/2 induction in MIA-OA rats. Conclusion Results of these studies support the role of MAPK activation in the progression and maintenance of central sensitization in the MIA-OA experimental pain model.

  15. Rotary pump speed modulation for generating pulsatile flow and phasic left ventricular volume unloading in a bovine model of chronic ischemic heart failure. (United States)

    Soucy, Kevin G; Giridharan, Guruprasad A; Choi, Young; Sobieski, Michael A; Monreal, Gretel; Cheng, Allen; Schumer, Erin; Slaughter, Mark S; Koenig, Steven C


    Rotary blood pumps operate at a constant speed (rpm) that diminishes vascular pulsatility and variation in ventricular end-systolic and end-diastolic volumes, which may contribute to adverse events, including aortic insufficiency and gastrointestinal bleeding. In this study, pump speed modulation algorithms for generating pulsatility and variation in ventricular end-systolic and end-diastolic volumes were investigated in an ischemic heart failure (IHF) bovine model (n = 10) using a clinically implanted centrifugal-flow left ventricular assist device (LVAD). Hemodynamic and hematologic measurements were recorded during IHF baseline, constant pumps speeds, and asynchronous (19-60 cycles/min) and synchronous (copulse and counterpulse) pump speed modulation profiles using low relative pulse speed (±25%) of 3,200 ± 800 rpm and high relative pulse speed (±38%) of 2,900 ± 1,100 rpm. End-organ perfusion, hemodynamics, and pump parameters were measured to characterize pulsatility, myocardial workload, and LVAD performance for each speed modulation profile. Speed modulation profiles augmented aortic pulse pressure, surplus hemodynamic energy, and end-organ perfusion (p Pump speed modulation increases pulsatility and improves cardiac function and end-organ perfusion, but the asynchronous mode provides the technologic advantage of sensorless control. Investigation of asynchronous pump speed modulation during long-term support is warranted to test the hypothesis that operating an LVAD with speed modulation will minimize adverse events in patients supported by an LVAD that may be associated with long-term operation at a constant pump speed. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  16. In vivo longitudinal study of rodent skeletal muscle atrophy using ultrasonography. (United States)

    Mele, Antonietta; Fonzino, Adriano; Rana, Francesco; Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Giustino, Arcangela; Conte Camerino, Diana; Desaphy, Jean-François


    Muscle atrophy is a widespread ill condition occurring in many diseases, which can reduce quality of life and increase morbidity and mortality. We developed a new method using non-invasive ultrasonography to measure soleus and gastrocnemius lateralis muscle atrophy in the hindlimb-unloaded rat, a well-accepted model of muscle disuse. Soleus and gastrocnemius volumes were calculated using the conventional truncated-cone method and a newly-designed sinusoidal method. For Soleus muscle, the ultrasonographic volume determined in vivo with either method was linearly correlated to the volume determined ex-vivo from excised muscles as muscle weight-to-density ratio. For both soleus and gastrocnemius muscles, a strong linear correlation was obtained between the ultrasonographic volume and the muscle fiber cross-sectional area determined ex-vivo on muscle cryosections. Thus ultrasonography allowed the longitudinal in vivo evaluation of muscle atrophy progression during hindlimb unloading. This study validates ultrasonography as a powerful method for the evaluation of rodent muscle atrophy in vivo, which would prove useful in disease models and therapeutic trials.

  17. Increasing internodal distance in myelinated nerves accelerates nerve conduction to a flat maximum. (United States)

    Wu, Lai Man N; Williams, Anna; Delaney, Ada; Sherman, Diane L; Brophy, Peter J


    Predictions that conduction velocities are sensitive to the distance between nodes of Ranvier in myelinated axons have implications for nervous system function during growth and repair. Internodal lengths defined by Schwann cells in hindlimb nerves, for example, can undergo a 4-fold increase during mouse development, and regenerated nerves have internodes that are uniformly short. Nevertheless, the influence of internodal length on conduction speed has limited experimental support. Here, we examined this problem in mice expressing a mutant version of periaxin, a protein required for Schwann cell elongation. Importantly, elongation of mutant Schwann cells was retarded without significant derangements to myelination or axon caliber. In young mice with short mutant Schwann cells, nerve conduction velocity was reduced and motor function was impaired. This demonstrates a functional relationship between internodal distance and conduction speed. Moreover, as internodes lengthened during postnatal growth, conduction velocities recovered to normal values and mutant mice exhibited normal motor and sensory behavior. This restoration of function confirms a further prediction by Huxley and Stämpfli that conduction speeds should increase as internodal distances lengthen until a "flat maximum" is reached, beyond which no further gains in conduction velocity accrue. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Forward Scattering of Loaded and Unloaded Antennas

    DEFF Research Database (Denmark)

    Gustafsson, Mats; Andersen, Jørgen Bach; Kristensson, Gerhard


    Forward scattering of antennas is related to antenna performance via the forward-scattering sum rule. The forward-scattering sum rule is an integral identity that shows that a weighted integral of the extinction cross section over all spectrum is proportional to the static polarizability...... of the antenna structure. Here, the forward-scattering sum rule is experimentally verified for loaded, short-circuit, and open-circuit cylindrical dipole antennas. It is also shown that the absorption efficiency cannot be greater than 1/2 for reciprocal linearly polarized lossless matched antennas...

  19. Response terminated displays unload selective attention

    Directory of Open Access Journals (Sweden)

    Zachary Joseph Jackson Roper


    Full Text Available Perceptual load theory successfully replaced the early versus late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load is sufficiently low to grant attentional ‘spill-over‘ to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional ‘spill-over’ by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented.

  20. Grain Unloading Of Arsenic Species In Rice (United States)

    Rice (Oryza sativa) is the staple food for over half the world's population yet may represent a significant dietary source of inorganic arsenic (As), a nonthreshold, class 1 human carcinogen. Rice grain As is dominated by the inorganic species, and the organic species dim...

  1. Emissions from Ships Unloading at a Dock (United States)

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  2. Preserved gait kinematics during controlled body unloading

    NARCIS (Netherlands)

    Awai, L.; Franz, M.; Easthope, C. S.; Vallery, H.; Curt, A; Bolliger, M


    Background: Body weight supported locomotor training was shown to improve walking function in neurological patients and is often performed on a treadmill. However, walking on a treadmill does not mimic natural walking for several reasons: absent self-initiation, less active retraction of leg

  3. Tetanic contraction induces enhancement of fatigability and sarcomeric damage in atrophic skeletal muscle and its underlying molecular mechanisms. (United States)

    Yu, Zhi-Bin


    Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of high-frequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1- and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus (EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase (nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated

  4. Recombinant sclerostin antagonises effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size. (United States)

    Kogawa, Masakazu; Khalid, Kamarul A; Wijenayaka, Asiri R; Ormsby, Renee T; Evdokiou, Andreas; Anderson, Paul H; Findlay, David M; Atkins, Gerald J


    Sclerostin (SCL) has emerged as an important regulator of bone mass. We have shown that SCL can act by targeting late osteoblasts/osteocytes to inhibit bone mineralisation and to upregulate osteocyte expression of catabolic factors, resulting in osteocytic osteolysis. Here we sought to examine the effect of exogenous sclerostin on osteocytes in trabecular bone mechanically loaded ex vivo. Bovine trabecular bone cores, with bone marrow removed, were inserted into individual chambers and subjected to daily episodes of dynamic loading. Cores were perfused with either osteogenic media alone or media containing human recombinant sclerostin (rhSCL) (50 ng/ml). Loaded control bone increased in apparent stiffness over time compared to unloaded bone, and this was abrogated in the presence of rhSCL. Loaded bone showed an increase in calcein uptake as a surrogate of mineral accretion, compared to unloaded bone, in which this was substantially inhibited by rhSCL treatment. Sclerostin treatment induced a significant increase in the ionised calcium concentration in the perfusate and the release of β-CTX at several time points, an increased mean osteocyte lacunar size, indicative of osteocytic osteolysis and the expression of catabolism-related genes. Human primary osteocyte-like cultures treated with rhSCL also released β-CTX from their matrix. These results suggest that osteocytes contribute directly to bone mineral accretion, and to the mechanical properties of bone. Moreover, it appears that sclerostin, acting on osteocytes, can negate this effect by modulating the dimensions of the lacunocanalicular porosity and the composition of the peri-osteocyte matrix. Copyright © 2017, American Journal of Physiology-Cell Physiology.

  5. Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity (United States)

    Delp, M. D.; Colleran, P. N.; Wilkerson, M. K.; McCurdy, M. R.; Muller-Delp, J.


    Hindlimb unloading of rats results in a diminished ability of skeletal muscle arterioles to constrict in vitro and elevate vascular resistance in vivo. The purpose of the present study was to determine whether alterations in the mechanical environment (i.e., reduced fluid pressure and blood flow) of the vasculature in hindlimb skeletal muscles from 2-wk hindlimb-unloaded (HU) rats induces a structural remodeling of arterial microvessels that may account for these observations. Transverse cross sections were used to determine media cross-sectional area (CSA), wall thickness, outer perimeter, number of media nuclei, and vessel luminal diameter of feed arteries and first-order (1A) arterioles from soleus and the superficial portion of gastrocnemius muscles. Endothelium-dependent dilation (ACh) was also determined. Media CSA of resistance arteries was diminished by hindlimb unloading as a result of decreased media thickness (gastrocnemius muscle) or reduced vessel diameter (soleus muscle). ACh-induced dilation was diminished by 2 wk of hindlimb unloading in soleus 1A arterioles, but not in gastrocnemius 1A arterioles. These results indicate that structural remodeling and functional adaptations of the arterial microvasculature occur in skeletal muscles of the HU rat; the data suggest that these alterations may be induced by reductions in transmural pressure (gastrocnemius muscle) and wall shear stress (soleus muscle).

  6. Simulated microgravity increases myocardial susceptibility to ischemia-reperfusion injury via a deficiency of AMP-activated protein kinase. (United States)

    Lu, Yuan-Ming; Jiao, Bo; Lee, Jun; Zhang, Lin; Yu, Zhi-Bin


    Gravitation is an important factor in maintaining cardiac contractility. Our study investigated whether simulated microgravity increases myocardial susceptibility to ischemia-reperfusion (IR) injury. Using the Langendorff-perfused heart model with 300 beats/min pacing, 4-week tail suspension (SUS) and control (CON) male Sprague-Dawley rats (n = 10 rats/group) were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 120 min of reperfusion. Left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, and infarct size were assessed. Data demonstrated that there were significantly increased LVEDP, CK, LDH, and infarct size in SUS compared with CON (P < 0.05), accompanied by decreased LVESP (P < 0.05). Furthermore, TUNEL-positive cardiomyocytes were higher in SUS than that in CON (P < 0.01), and AMP-activated protein kinase (AMPK) phosphorylation and Bcl-2/Bax in SUS were less compared with CON (P < 0.05). Similarly, isolated hearts pre-treated with A-769662 exhibited better recovery of cardiac function, increased AMPK phosphorylation, and reduced necrosis and apoptosis. Furthermore, AMPKα protein showed a significant suppression in 4-week hindlimb unweighting rats. These results suggest that AMPK deficiency increases myocardial susceptibility to IR injury in rats subjected to simulated microgravity.

  7. Characterization of disuse skeletal muscle atrophy and the efficacy of a novel muscle atrophy countermeasure during spaceflight and simulated microgravity (United States)

    Hanson, Andrea Marie

    Humans are an integral part of the engineered systems that will enable return to the Moon and eventually travel to Mars. Major advancements in countermeasure development addressing deleterious effects of microgravity and reduced gravity on the musculoskeletal system need to be made to ensure mission safety and success. The primary objectives of this dissertation are to advance the knowledge and understanding of skeletal muscle atrophy, and support development of novel countermeasures for disuse atrophy to enable healthy long-duration human spaceflight. Models simulating microgravity and actual spaceflight were used to examine the musculoskeletal adaptations during periods of unloading. Myostatin inhibition, a novel anti-atrophy drug therapy, and exercise were examined as a means of preventing and recovering from disuse atrophy. A combination of assays was used to quantify adaptation responses to unloading and examine efficacy of the countermeasures. Body and muscle masses were collected to analyze systemic changes due to treatments. Hindlimb strength and individual muscle forces were measured to demonstrate functional adaptations to treatments. Muscle fiber morphology and myosin heavy chain (MHC) expression was examined to identify adaptations at the cellular level. Protein synthesis signals insulin-like growth factor-1 (IGF-1), Akt, and p70s6 kinase; and the degradation signals Atrogin-1 and MuRF-1 were examined to identify adaptations at the molecular level that ultimately lead to muscle hypertrophy and atrophy. A time course study provided a thorough characterization of the adaptation of skeletal muscle during unloading in C57BL/6 mice, and baseline data for comparison to and evaluation of subsequent studies. Time points defining the on-set and endpoints of disuse muscle atrophy were identified to enable characterization of rapid vs. long-term responses of skeletal muscle to hindlimb suspension. Unloading-induced atrophy primarily resulted from increased protein

  8. Simulated weightlessness and synbiotic diet effects on rat bone mechanical strength (United States)

    Sarper, Hüseyin; Blanton, Cynthia; DePalma, Jude; Melnykov, Igor V.; Gabaldón, Annette M.


    This paper reports results on exposure to simulated weightlessness that leads to a rapid decrease in bone mineral density known as spaceflight osteopenia by evaluating the effectiveness of dietary supplementation with synbiotics to counteract the effects of skeletal unloading. Forty adult male rats were studied under four different conditions in a 2 × 2 factorial design with main effects of diet (synbiotic and control) and weight condition (unloaded and control). Hindlimb unloading was performed at all times for 14 days followed by 14 days of recovery (reambulation). The synbiotic diet contained probiotic strains Lactobacillus acidophilus and Lactococcus lactis lactis and prebiotic fructooligosaccharide. This paper also reports on the development of a desktop three-point bending device to measure the mechanical strength of bones from rats subjected to simulated weightlessness. The importance of quantifying bone resistance to breakage is critical when examining the effectiveness of interventions against osteopenia resulting from skeletal unloading, such as astronauts experience, disuse or disease. Mechanical strength indices provide information beyond measures of bone density and microarchitecture that enhance the overall assessment of a treatment's potency. In this study we used a newly constructed three-point bending device to measure the mechanical strength of femur and tibia bones from hindlimb-unloaded rats fed an experimental synbiotic diet enriched with probiotics and fermentable fiber. Two calculated outputs for each sample were Young's modulus of elasticity and fracture stress. Bone major elements (calcium, magnesium, and phosphorous) were quantified using ICP-MS analysis. Hindlimb unloading was associated with a significant loss of strength in the femur, and with significant reductions in major bone elements. The synbiotic diet did not protect against these unloading effects. Tibia strength and major elements were not reduced by hindlimb unloading, as was

  9. Increasingly minimal bias routing (United States)

    Bataineh, Abdulla; Court, Thomas; Roweth, Duncan


    A system and algorithm configured to generate diversity at the traffic source so that packets are uniformly distributed over all of the available paths, but to increase the likelihood of taking a minimal path with each hop the packet takes. This is achieved by configuring routing biases so as to prefer non-minimal paths at the injection point, but increasingly prefer minimal paths as the packet proceeds, referred to herein as Increasing Minimal Bias (IMB).

  10. Increasing SLEDed Linac Gradient

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, Zoltan D


    This note will show how to increase the SLED [1] gradient by varying Q{sub e}, the external Q of the SLED cavity, by increasing its Q{sub 0} and by increasing the compression ratio. If varying the external Q is to be effective, then the copper losses should be small so that Q{sub 0} >> Q{sub e}. Methods of varying Q{sub e} will be indicated but no experimental data will be presented. If we increase the klystron pulse width from 3.5 to 5 {micro}S and increase Q{sub 0} from the present 100000 to 300000, then the gradient increases by 19% and the beam energy increases from 50 to 60 GeV. This note will also discuss SLED operation at 11424 MHz, the NLC frequency. Without Q{sub e} switching, using SLED at 11424 MHz increases the SLAC gradient from 21 MV/m to 34 MV/m, and at the same repetition rate, uses about 1/5 of rf average power. If we also double the compression ratio, we reach 47 MV/m and over 100 GeV beam energy.

  11. Increasing Public Expenditure

    Directory of Open Access Journals (Sweden)

    Ammar Ben Zaed


    Full Text Available This article aims to analyze and interpret the phenomenon of increased public expenditures and test explanatory theories as well as to analyze Abstract the relationship between public spending and GDP in the short and long term where you see the Wagner hypothesis that causal heading of GDP to government spending while there is a causal relationship analysis positive trending of government spending to GDP according to the Keynesian hypothesis in this study will be used descriptive analytical method to validate these hypotheses. Results in the short and long term made it clear that there is a difference in the outcome of Applied Studies where we find that each supports a relationship Wagner in the sense that the causal trending of real GDP to government spending and more precisely to increase the economic growth lead to increased aggregate demand which leads in turn increasing the need to increase government spending and to increase the resources available to the government sector to finance the increase in spending by the additional resources resulting from the economic growth while others opines opposes the existence of the relationship.

  12. Rapid insulin-mediated increase in microvascular glycocalyx accessibility in skeletal muscle may contribute to insulin-mediated glucose disposal in rats. (United States)

    Eskens, Bart J M; Mooij, Hans L; Cleutjens, Jack P M; Roos, Jozef M A; Cobelens, Johanna E; Vink, Hans; Vanteeffelen, Jurgen W G E


    It has been demonstrated that insulin-mediated recruitment of microvascular blood volume is associated with insulin sensitivity. We hypothesize that insulin rapidly stimulates penetration of red blood cells (RBC) and plasma into the glycocalyx and thereby promotes insulin-mediated glucose uptake by increasing intracapillary blood volume. Experiments were performed in rats; the role of the glycocalyx was assessed by enzymatic degradation using a bolus of hyaluronidase. First, the effect of insulin on glycocalyx accessibility was assessed by measuring the depth of penetration of RBCs into the glycocalyx in microvessels of the gastrocnemius muscle with Sidestream Dark-field imaging. Secondly, peripheral insulin sensitivity was determined using intravenous insulin tolerance tests (IVITT). In addition, in a smaller set of experiments, intravital microscopy of capillary hemodynamics in cremaster muscle and histological analysis of the distribution of fluorescently labeled 40 kDa dextrans (D40) in hindlimb muscle was used to evaluate insulin-mediated increases in capillary blood volume. Insulin increased glycocalyx penetration of RBCs by 0.34±0.44 µm (Pglucose disposal compared to control rats. Insulin-mediated increases in capillary blood volume were reflected by a rapid increase in capillary tube hematocrit from 21.1±10.1% to 29.0±9.8% (Pblood in muscle, and this is associated with an increased blood volume in individual capillaries. Hyaluronidase treatment of the glycocalyx abolishes the effects of insulin on capillary blood volume and impairs insulin-mediated glucose disposal.

  13. Increased intracranial pressure (United States)

    ... by pressing on important structures and by restricting blood flow into the brain. Many conditions can increase intracranial pressure. Common causes include: Aneurysm rupture and subarachnoid hemorrhage Brain tumor Encephalitis Head ...

  14. Increasing productivity: Another approach

    Energy Technology Data Exchange (ETDEWEB)

    Norton, F.J.


    An engineering information (EI) and information technology (IT) organization that must improve its productivity should work to further its business goals. This paper explores a comprehensive model for increasing EI/IT productivity by supporting organizational objectives.

  15. Increased urinary orosomucoid excretion

    DEFF Research Database (Denmark)

    Christiansen, M S; Iversen, K; Larsen, C T


    OBJECTIVE: In a previous study, urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes. The aim of the present study was to determine whether increased UOER is associated with cardiovascular risk factors such as inflammation......, impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. MATERIAL AND METHODS: We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy...... with type 2 diabetes, UOER was independently associated with increasing values of IL-6 (1.43 (1.06-1.93)) and tPA (1.82 (1.20-2.77)). Measurements by echocardiography showed no signs of cardiac dysfunction. CONCLUSIONS: Asymptomatic patients with type 2 diabetes and increased UOER displayed signs of chronic...

  16. Meeting increased demand. (United States)

    Blair, Andrew


    New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

  17. The adaptation of limb kinematics to increasing walking speeds in freely moving mice 129/Sv and C57BL/6. (United States)

    Serradj, Nadjet; Jamon, Marc


    The kinematics of locomotion was analyzed in two strains of great importance for the creation of mutated mice (C56BL/6 and 129/Sv). Different behavioral situations were used to trigger sequences of movement covering the whole range of velocities in the mice, and the variations of kinematic parameters were analyzed in relation with velocity. Both stride frequency and stride length contributed to the moving speed, but stride frequency was found to be the main contributor to the speed increase. A trot-gallop transition was detected at speed about 70 cm/s, in relation with a sharp shift in limb coordination. The results of this study were consistent with pieces of information previously published concerning the gait analyses of other strains, and provided an integrative view of the basic motor pattern of mice. On the other hand some qualitative differences were found in the movement characteristics of the two strains. The stride frequency showed a higher contribution to speed in 129/Sv than in C57BL/6. In addition, 129/Sv showed a phase shift in the forelimb and hindlimb, and a different position of the foot during the stance time that revealed a different gait and body position during walking. Overall, 129/Sv moved at a slower speed than C57BL/6 in any behavioral situation. This difference was related to a basal lower level of motor activity. The possibility that an alteration in the dopamine circuit was responsible for the different movement pattern in 129/Sv is discussed.

  18. Hypoxia increases mouse satellite cell clone proliferation maintaining both in vitro and in vivo heterogeneity and myogenic potential. (United States)

    Urbani, Luca; Piccoli, Martina; Franzin, Chiara; Pozzobon, Michela; De Coppi, Paolo


    Satellite cells (SCs) are essential for postnatal muscle growth and regeneration, however, their expansion potential in vitro is limited. Recently, hypoxia has been used to enhance proliferative abilities in vitro of various primary cultures. Here, by isolating SCs from single mouse hindlimb skeletal myofibers, we were able to distinguish two subpopulations of clonally cultured SCs (Low Proliferative Clones--LPC--and High Proliferative Clones--HPC), which, as shown in rat skeletal muscle, were present at a fixed proportion. In addition, culturing LPC and HPC at a low level of oxygen we observed a two fold increased proliferation both for LPC and HPC. LPC showed higher myogenic regulatory factor (MRF) expression than HPC, particularly under the hypoxic condition. Notably, a different myogenic potential between LPC and HPC was retained in vivo: green fluorescent protein (GFP)+LPC transplantation in cardiotoxin-injured Tibialis Anterior led to a higher number of new GFP+muscle fibers per transplanted cell than GFP+HPC. Interestingly, the in vivo myogenic potential of a single cell from an LPC is similar if cultured both in normoxia and hypoxia. Therefore, starting from a single satellite cell, hypoxia allows a larger expansion of LPC than normal O(2) conditions, obtaining a consistent amount of cells for transplantation, but maintaining their myogenic regeneration potential.

  19. Whole-body-vibration-induced increase in leg muscle activity during different squat exercises. (United States)

    Roelants, Machteld; Verschueren, Sabine M P; Delecluse, Christophe; Levin, Oron; Stijnen, Valère


    This study analyzed leg muscle activity during whole-body vibration (WBV) training. Subjects performed standard unloaded isometric exercises on a vibrating platform (Power Plate): high squat (HS), low squat (LS), and 1-legged squat (OL). Muscle activity of the rectus femoris, vastus lateralis, vastus medialis, and gastrocnemius was recorded in 15 men (age 21.2 +/- 0.8 years) through use of surface electromyography (EMG). The exercises were performed in 2 conditions: with WBV and without (control [CO]) a vibratory stimulus of 35 Hz. Muscle activation during WBV was compared with CO and with muscle activation during isolated maximal voluntary contractions (MVCs). Whole-body vibration resulted in a significantly higher (p < 0.05) EMG root-mean-square compared with CO in all muscle groups and all exercises (between +39.9 +/- 17.5% and +360.6 +/- 57.5%). The increase in muscle activity caused by WBV was significantly higher (p < 0.05) in OL compared with HS and LS. In conclusion, WBV resulted in an increased activation of the leg muscles. During WBV, leg muscle activity varied between 12.6 and 82.4% of MVC values.

  20. Increasing income inequality

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Poulsen, Odile

    In recent decades most developed countries have experienced an increase in income inequality. In this paper, we use an equilibrium search framework to shed additional light on what is causing an income distribution to change. The major benefit of the model is that it can accommodate shocks...... to the skill composition in the market, employee bargaining power and productivity. Further, when our model is subjected to skill-upgrading and changes in employee bargaining power, it is capable of predicting the recent changes observed in the Danish income distribution. In addition, the model emphasizes...... that shocks to the employees' relative productivity, i.e., skill-biased technological change, are unlikely to have caused the increase in income inequality....

  1. Nifedipine increases fetoplacental perfusion. (United States)

    Karahanoglu, Ertugrul; Altinboga, Orhan; Akpinar, Funda; Demirdag, Erhan; Ozdemirci, Safak; Akyol, Aysegul; Yalvac, Serdar


    Our aim is to evaluate the effect of nifedipine on fetoplacental hemodynamic parameters. A retrospective study was conducted at a tertiary center with 30 patients for whom nifedipine treatment was used as a tocolytic therapy for preterm labor. Initiation of this treatment was at 31.6±2.5 weeks of gestation. We combined the pulse Doppler imaging parameters with grayscale imaging via the Bernoulli theorem, which is called the "continuity equation", to get the fetoplacental perfusion (FPP). Evaluated parameters were the resistance index (RI), the pulsatility index (PI), systole/diastole ratios (S/D), the velocity-time integral of the umbilical artery (VTI), the radius of the umbilical artery, the peak systolic velocity and the mean pressure gradient in the umbilical artery. From these parameters, the FPP was acquired. We found that the RI, the PI and the S/D ratio did not change after treatment with nifedipine. The mean pressure gradient, the VTI and the peak systolic velocity increased after treatment with nifedipine. Nifedipine increases FPP from 166±73.81 beat.cm3/min to 220±83.3 beat.cm3/min. Although nifedipine had no effect on the PI, the RI or the S/D, it increased the mean pressure gradient, the VTI and FPP.

  2. Increasing student success (United States)

    Stewart, Gay; Stewart, John


    A more scientifically literate society benefits all STEM disciplines, as well as society as a whole. It is best realized by better serving all undergraduate STEM students. In better-serving all students, a physics department also benefits. The University of Arkansas, Fayetteville physics department has seen a drastic change in number of majors, the number of students active in research and the number of graduates pursuing graduate work, while also increasing the number of majors who decide to teach. Prior to our involvement with the Physics Teacher Education Coalition, graduation rates had increased by more than a factor of 4 in 4 years. After the increased efforts when we became a part of PhysTEC ( our graduation numbers doubled again. Specific attention to class policy to impact student learning in our introductory courses and strong preparation of the graduate teaching assistants, and quality advising were our primary areas of emphasis. What worked to build these numbers and strengthen these resources at Arkansas will be discussed. This work was supported in part by the National Science Foundation and through the Physics Teacher Education Coalition.

  3. Responses of Myosin Heavy Chain Phenotypes and Gene Expressions in Neck Muscle to Micro- an Hyper-Gravity in Mice (United States)

    Ohira, Tomotaka; Ohira, Takashi; Kawano, F.; Shibaguchi, T.; Okabe, H.; Ohno, Y.; Nakai, N.; Ochiai, T.; Goto, K.; Ohira, Y.


    Neck muscles are known to play important roles in the maintenance of head posture against gravity. However, it is not known how the properties of neck muscle are influenced by gravity. Therefore, the current study was performed to investigate the responses of neck muscle (rhomboideus capitis) in mice to inhibition of gravity and/or increase to 2-G for 3 months to test the hypothesis that the properties of neck muscles are regulated in response to the level of mechanical load applied by the gravitational load. Three male wild type C57BL/10J mice (8 weeks old) were launched by space shuttle Discovery (STS-128) and housed in Japanese Experimental Module “KIBO” on the International Space Station in mouse drawer system (MDS) project, which was organized by Italian Space Agency. Only 1 mouse returned to the Earth alive after 3 months by space shuttle Atlantis (STS-129). Neck muscles were sampled from both sides within 3 hours after landing. Cage and laboratory control experiments were also performed on the ground. Further, 3-month ground-based control experiments were performed with 6 groups, i.e. pre-experiment, 3-month hindlimb suspension, 2-G exposure by using animal centrifuge, and vivarium control (n=5 each group). Five mice were allowed to recover from hindlimb suspension (including 5 cage control) for 3 months in the cage. Neck muscles were sampled bilaterally before and after 3-month suspension and 2-G exposure, and at the end of 3-month ambulation recovery. Spaceflight-associated shift of myosin heavy chain phenotype from type I to II and atrophy of type I fibers were observed. In response to spaceflight, 17 genes were up-regulated and 13 genes were down-regulated vs. those in the laboratory control. Expression of 6 genes were up-regulated and that of 88 genes were down-regulated by 3-month exposure to 2-G vs. the age-matched cage control. In response to chronic hindlimb suspension, 4 and 20 genes were up- or down-regulated. Further, 98 genes responded

  4. Global Increases in Individualism. (United States)

    Santos, Henri C; Varnum, Michael E W; Grossmann, Igor


    Individualism appears to have increased over the past several decades, yet most research documenting this shift has been limited to the study of a handful of highly developed countries. Is the world becoming more individualist as a whole? If so, why? To answer these questions, we examined 51 years of data on individualist practices and values across 78 countries. Our findings suggest that individualism is indeed rising in most of the societies we tested. Despite dramatic shifts toward greater individualism around the world, however, cultural differences remain sizable. Moreover, cultural differences are primarily linked to changes in socioeconomic development, and to a lesser extent to shifts in pathogen prevalence and disaster frequency.

  5. Anodization increases early integration of Osstem implants in sheep femurs. (United States)

    Duncan, Warwick J; Lee, Min Ho; Dovban, Alex S M; Hendra, Nicholas; Ershadi, Sara; Rumende, Heny


    Spark discharge anodic oxidation forms a porous TiO2 film on the surface of titanium oral implants, increasing surface roughness and concentrations of calcium and phosphate ions. In this study, anodic-treated oral implants were placed in an animal model and analysed using clinical, micro-computerized tomographic (micro-CT) and histometric techniques. Pairs of 3.5 mm x 8.5 mm long titanium implants (Osstem Implant Co., Ltd. Seoul, Korea), with blasted (control) or blasted and oxidized surfaces (test), were placed into the right femoral condyles of 10 sheep. Animals were sacrificed after 1 month unloaded healing. Resonant frequency analysis (RFA) was measured in implant stability quotient (ISQ) using the Mentor II device. Specimens were scanned using medium resolution micro-CT (Skyscan 1172). Mean percent bone-to-implant contact (%BIC) was calculated from two images per implant by three different operators, using Image J software. Inter- and intra-examiner differences were calculated. Specimens were then embedded in methacrylate and undemineralized ground sections were digitized. Mean %BIC was measured using Image J at x 20 magnification for the best-three consecutive threads from the most central section. Mean micro-CT %BIC was similar for control and test (57.2 +/- 0.05% versus 56.4 +/- 0.03%, p = 0.5). There was considerable inter-examiner variability (interclass correlation coefficient = 0.44). RFA showed no clinically-detectable difference between the two groups (control ISQ: 75.2 +/- 4.2; test ISQ: 76.3 +/- 1.7; p = 0.48). However, histometric analysis found a marked and highly statistically-significant difference (%BIC Test 72.5 +/- 8.6%, Control 46.2 +/- 12.1%, p = 0.01). The novel anodic oxidation technique increased early ossointegration of rough-surfaced implants by 157%. Neither clinical testing with resonant frequency analysis nor radiographic analysis using micro-CT had sufficient resolution to detect this improvement. Whether this gain in early bone

  6. Macrophage invasion does not contribute to muscle membrane injury during inflammation (United States)

    Tidball, J. G.; Berchenko, E.; Frenette, J.


    Previous observations have shown that neutrophil invasion precedes macrophage invasion during muscle inflammation and that peak muscle injury is observed at the peak of ED1+ macrophage invasion. We tested the hypothesis that neutrophil invasion causes subsequent invasion by ED1+ macrophages and that ED1+ macrophages then contribute significantly to muscle membrane injury during modified muscle use. Rat hindlimbs were unloaded for 10 days followed by reloading by normal ambulation to induce inflammation. Membrane injury was measured by assaying Evans blue-bound serum protein influx through membrane lesions. Muscle neutrophil populations increased significantly during the first 2 h of reloading but ED1+ macrophages did not increase until 24 h. Neutrophil invasion was uncoupled from subsequent macrophage invasion by reloading rat hindlimbs for 2 h to cause neutrophil invasion, followed by resuspension for hours 2-24. This produced similar increases in neutrophil concentration as measured in muscles continuously reloaded for 24 h without causing an increase in macrophages. However, resuspension did not reduce the extent of muscle damage compared with that occurring in muscles that were reloaded continuously for 24 h. Thus, muscle invasion by neutrophils is not sufficient to cause invasion by ED1+ macrophages. In addition, muscle membrane injury that occurs during reloading is independent of invasion by ED1+ macrophages.

  7. Increasing Possibilities of Nanosuspension

    Directory of Open Access Journals (Sweden)

    Kumar Bishwajit Sutradhar


    Full Text Available Nowadays, a very large proportion of new drug candidates emerging from drug discovery programmes are water insoluble and thus poorly bioavailable. To avoid this problem, nanotechnology for drug delivery has gained much interest as a way to improve the solubility problems. Nano refers to particles size range of 1–1000 nm. The reduction of drug particles into the submicron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are part of nanotechnology. This interacts with the body at subcellular (i.e., molecular scales with a high degree of specificity and can be potentially translated into targeted cellular and tissue-specific clinical applications designed to achieve maximal therapeutic efficacy with minimal side effects. Production of drugs as nanosuspensions can be developed for drug delivery systems as an oral formulation and nonoral administration. Here, this review describes the methods of pharmaceutical nanosuspension production including advantages and disadvantages, potential benefits, characterization tests, and pharmaceutical applications in drug delivery.

  8. Stress increases periodontal inflammation (United States)



    This study aimed to examine the effect of chronic restraint stress (RS) on the severity of experimental periodontal disease in rats. A total of 32 male Sprague Dawley (SD) rats were divided into four groups: i) Rats receiving two treatment regimens, chronic stress induced by movement restriction in acrylic cylinders for 1–1.5 h daily and induction of experimental periodontal disease, using a nylon ligature which was placed around the first left mandibular molars (n=8); ii) induction of periodontal disease, without RS (n=8); iii) RS (n=8) and iv) control (n=8). After 15 days, blood samples were obtained, and blood glucose levels and the corticosterone concentration were measured as stress markers. The severity of periodontal disease was analyzed according to the level of gingival and bone inflammation, leading to compromise of the teeth involved. Chronic stress was induced with movement restriction (P≤0.05, Mann-Whitney U-test) and increased the severity (P≤0.05, Mann-Whitney U-test) of experimental perio dontal disease in rats, according to the level of gingival and bone inflammation around the first left mandibular molars. The results of the present study showed that RS modulates periodontal inflammation and that the rat model described herein is suitable for investigating the association between stress and periodontal disease. PMID:23226743

  9. Effects of long-duration bed rest on structural compartments of m. soleus in man (United States)

    Belozerova, I.; Shenkman, B.; Mazin, M.; Leblanc, A.; LeBlanc, A. D. (Principal Investigator)


    Magnetic resonance imaging (MRI), histomorphometry and electron microscopy of muscle demonstrate that long-term exposure to actual or simulated weightlessness (including head down bed rest) leads to decreased volume of antigravity muscles in mammals. In muscles interbundle space is occupied by the connective tissue. Rat studies show that hindlimb unloading induces muscle fiber atrophy along with increase in muscle non-fiber connective tissue compartment. Beside that, usually 20% of the muscle fiber volume is comprised by non-contractile (non-myofibrillar) compartment. The aim of the present study was to compare changes in muscle volume, and in muscle fiber size with alterations in myofibrillar apparatus, and in connective tissue compartment in human m. soleus under conditions of 120 day long head down bed rest (HDBR).

  10. The evolution of elastic moduli with increasing crack damage during cyclic stressing of a basalt from Mt. Etna volcano (United States)

    Heap, M. J.; Vinciguerra, S.; Meredith, P. G.


    Volcanic edifices, such as Mt. Etna (Italy), are commonly subject to repeated cycles of stress over time due to the combination of magma emplacement from deep reservoirs to shallow depths and superimposed tectonic stresses. Such repeated stress cycles lead to anisotropic deformation and an increase in the level of crack damage within the rocks of the edifice and hence changes to their elastic moduli, which are a key parameter for reliable modelling of deformation sources. We therefore report results of changes in elastic moduli measured during increasing amplitude cyclic stressing experiments on dry and water-saturated samples of Etna basalt. In all experiments, the Young's modulus decreased by approximately 30% over the total sequence of loading cycles, and the Poisson's ratio increased by a factor of approximately 3 ± 0.5. Microseismicity, in terms of acoustic emission (AE) output, was also recorded throughout each experiment. Our results demonstrate that AE output only re-commences during any loading cycle when the level of stress where AE ceased during the unloading portion of the previous cycle is exceeded; a manifestation of the Kaiser stress-memory effect. In cycles where no AE output was generated, we also observed no change in elastic moduli. This result holds for both mechanical and thermal stressing. Our results are interpreted in relation to measurements of volcano-tectonic seismicity and deformation at Mt. Etna volcano.

  11. In vivo locomotor strain in the hindlimb bones of alligator mississippiensis and iguana iguana: implications for the evolution of limb bone safety factor and non-sprawling limb posture (United States)

    Blob; Biewener


    Limb postures of terrestrial tetrapods span a continuum from sprawling to fully upright; however, most experimental investigations of locomotor mechanics have focused on mammals and ground-dwelling birds that employ parasagittal limb kinematics, leaving much of the diversity of tetrapod locomotor mechanics unexplored. This study reports measurements of in vivo locomotor strain from the limb bones of lizard (Iguana iguana) and crocodilian (Alligator mississippiensis) species, animals from previously unsampled phylogenetic lineages with non-parasagittal limb posture and kinematics. Principal strain orientations and shear strain magnitudes indicate that the limb bones of these species experience considerable torsion during locomotion. This contrasts with patterns commonly observed in mammals, but matches predictions from kinematic observations of axial rotation in lizard and crocodilian limbs. Comparisons of locomotor load magnitudes with the mechanical properties of limb bones in Alligator and Iguana indicate that limb bone safety factors in bending for these species range from 5.5 to 10.8, as much as twice as high as safety factors previously calculated for mammals and birds. Limb bone safety factors in shear (3.9-5.4) for Alligator and Iguana are also moderately higher than safety factors to yield in bending for birds and mammals. Finally, correlations between limb posture and strain magnitudes in Alligator show that at some recording locations limb bone strains can increase during upright locomotion, in contrast to expectations based on size-correlated changes in posture among mammals that limb bone strains should decrease with the use of an upright posture. These data suggest that, in some lineages, strain magnitudes may not have been maintained at constant levels through the evolution of a non-sprawling posture unless the postural change was accompanied by a shift to parasagittal kinematics or by an evolutionary decrease in body size.

  12. Comparison of excitability parameters and sodium channel behavior of fast- and slow-twitch rat skeletal muscles for the study of the effects of hindlimb suspension, a model of hypogravity. (United States)

    Desaphy, J F; Pierno, S; Liantonio, A; De Luca, A; Leoty, C; Conte Camerino, D


    When mammals are constrained to hypogravity, their neuromuscular apparatus undergoes modifications which rend difficult postural maintenance and muscular activity upon the return to normal gravitational conditions. Muscle atrophy and differetial gene expression are particularly evident in slow-twitch antigravity muscles such as the soleus. During hypogravity, most of the metabolic and contractile properties characteristic of slow-twitch muscles shift toward to those of fast-twitch muscles. For example, the expression of the fast isoforms of both the myosin heavy-chain and the sarcoplasmic reticulum calcium pump increases in slow-twitch muscle during hypogravity. Thus, modifications of the contractile machinery and calcium handling are likely to be involved in the hypogravity-induced slow-twitch muscle impariment. Fast- and slow-twitch muscles differ also in their electrical properties. Resting membrane potential (RMP) is more negative by about 10 mV in fast muscles compared to slow ones. Differences in action potential (AP) shape as well as in the number of elicitable APs have been also observed between both muscle types, which may reslut from the reported differences in chloride conductance and sodium current. Little is known about the potential modification fo muscle electrical properties during hypogravity, apart a negative shift of the RMP in soleus muscle. Thus this study was performed at the aim to compare the excitability parameters and sodium channel behavior of rat fast-twitch and slow-twitch muscle fibers. The characterization of these properties specific for each muscle-type will give us the basis for the study of the effect of hypogravity.

  13. Postnatal training of 129/Sv mice confirms the long-term influence of early exercising on the motor properties of mice. (United States)

    Serradj, Najet; Jamon, Marc


    A previous study showed that motor experiences during critical periods of development durably affect the motor properties of adult C57BL/6J mice. However, dependence on early environmental features may vary with the genetic profile. To evaluate the contribution of the genetic background on external influences to motricity, we performed the same experiment in a 129/Sv mouse strain that show a strongly different motor profile. Mice were subjected to endurance training (enriched environment or forced treadmill), hypergravity (chronic centrifugation), or simulated microgravity (hindlimb unloading) between postnatal days 10 and 30. They were then returned to standard housing until testing at the age of nine months. The endurance-trained mice showed a fast-slow shift in the deep zone of the tibialis. In addition, mice reared in the enriched environment showed a modified gait and body posture, and improved performance on the rotarod, whereas forced treadmill training did not affect motor output. Hypergravity induced a fast-slow shift in the superficial zone of the tibialis, with no consequence on motor output. Hindlimb unloading provoked an increased percentage of immature hybrid fibres in the tibialis and a shift in the soleus muscle. When compared with similarly reared C57BL/6J mice, 129/Sv mice showed qualitative differences attributable to the lower efficiency of early training due to their lower basal motor activity level. Nevertheless, the results are essentially consistent in both strains, and support the hypothesis that early motor experience influences the muscle phenotype and motor output. Copyright © 2016. Published by Elsevier B.V.

  14. Alterations in Skel